Download Volume 2, Number 4, Summer 2012

Cancer Update
Charles A. Sammons Cancer Center at Dallas
Baylor Charles A. Sammons
Cancer Center’s Research
Grant Program: Jumpstarting
Tomorrow’s Discoveries
Origin and Development of the Program
Baylor Health Care System is dedicated to the improvement of patient
care. For cancer patients, a critical strategy in attaining this goal is
promoting medical research to develop better approaches for the
diagnosis, treatment, and prevention of cancer. Thus, with the support
of Baylor Health Care System Foundation, funding was established to
support oncology research throughout the system. Beginning in 1996,
applications for funding from this program were reviewed
by Baylor Charles A. Sammons Cancer Center’s
Research Review Committee. This committee was
chaired by Marvin J. Stone, MD, MACP, who served as
chief of oncology at Baylor University Medical Center at
Dallas and director of Baylor Sammons Cancer Center
from 1976 to 2008; it included the administrative vice
president for Baylor Research Institute (BRI) as well as
established cancer investigators from throughout Baylor.
A formal peer-review procedure was established for the
committee to review funding requests; if they decided a
request had merit, it was sent for outside review before
funds were allocated for the research. This program
funded many oncology projects at Baylor.
This was the program in place when Alan M. Miller, MD,
PhD, first arrived in Dallas in late 2008 to serve as chief
(Continued on page 3)
Volume 2 • Number 4 • Summer 2012
In This Issue
2 From the Director
5 Hope for Advanced Melanoma:
New Developments in Cancer Vaccines
6 Upcoming Meetings of Interest to
Oncologists
7 One-day Symposia Provide Updates for Medical Professionals
8 Focus on Locally Advanced Breast Cancer:
New Insights, New Treatments
10 Precision Medicine Targets the Prevention
and Treatment of Colorectal Carcinoma
13 Cancer Center Grants for Trainees and
New Investigators
15 Clinical Trials on the Baylor Dallas Campus
20 Site-specific Tumor Conferences
21Publications
23 Fourth Annual Stone Lectureship
2 Baylor Sammons Cancer Center CancerUpdate
Cancer UPDATE
From the Director
Investing in Research
Volume 2 • Number 4 • Summer 2012
CancerUpdate is a publication of Baylor
Charles A. Sammons Cancer Center at Dallas,
Baylor University Medical Center at Dallas.
BaylorHealth.edu/Sammons
214.820.3535
Editor in Chief: Alan M. Miller, MD, PhD
Chief of Oncology, Baylor Health Care System
Medical Director, Baylor Charles A. Sammons
Cancer Center at Dallas
Managing Editor: Jana Pope
Writers and Assistant Editors: Lorraine Cherry, PhD
and Margaret Hinshelwood, PhD
To be removed from the mailing list, call
1.800.9BAYLOR.
Physicians are members of the medical staff at
one of Baylor Health Care System’s subsidiary,
community, or affiliated medical centers and are
neither employees nor agents of those medical
centers, Baylor University Medical Center at
Dallas, or Baylor Health Care System.
Cancer research studies on the campus of Baylor
University Medical Center at Dallas are conducted
through Baylor Research Institute, Texas Oncology,
and US Oncology. Each reviews, approves, and
conducts clinical trials independently.
Copyright © 2012, Baylor Health Care System.
All rights reserved. SAMMONS_369_2012 DH
Baylor Charles A. Sammons
Cancer Center at Dallas
214.820.3535 or 1.800.9BAYLOR
BaylorHealth.edu/Sammons
Our referral, consult, and information line
offers easy access for:
• Physician referrals
• Follow-up on patients to referring
physicians
• Medical records
• Information on clinical trials
• Specialized services
• New patient information, maps and
lodging information
Richard Brinsley Sheridan, the 18th century Irish
playwright who wrote The School for Scandal, was
quoted as saying, “Fertilizer does no good in a heap,
but a little spread around works miracles all over.”
The same might be said for allocating resources to
support research. It does little good to accumulate
them and “leave them in a heap” when we can
distribute them and hopefully facilitate some miracles.
We have endeavored to use the funds entrusted to us
through philanthropy to foster research. Over the past
2½ years we have awarded more than $1.5 million in
this effort.
Alan M. Miller, MD, PhD
chief of oncology,
Baylor Health Care
System and medical
director, Baylor
Charles A. Sammons
Cancer Center at Dallas
On the following pages, we describe six different
research programs designed to help investigators
at Baylor Charles A. Sammons Cancer Center at
Dallas generate the preliminary data needed to compete successfully for
external funding. We also highlight the investigators whose studies have
been funded by these programs and the progress they have achieved in
their results, publications, and funding efforts. Particularly exciting is the
trainee awards program that encourages young physicians and scientists
to choose a path that leads them to investigation, specifically in cancerrelated research. The fact that the first of these awards went to a
nephrology fellow who chose a cancer-related project was personally
satisfying and will hopefully encourage others from a broad spectrum of
specialties to look for these opportunities and become more involved in
the cancer center.
The projects to date have been diverse and well designed. We are
currently awaiting the next round of applications and the opportunity to
stimulate some miracles that will one day benefit our patients.
Baylor Sammons Cancer Center CancerUpdate 3
(Continued from page 1)
of oncology at Baylor Dallas and medical director of Baylor
Sammons Cancer Center. Dr. Miller came with a plan for
significantly increasing the amount of oncology research
conducted at Baylor. In early 2009, he restructured Baylor
Sammons Cancer Center’s Research Grant Program: the
Research Review Committee was replaced with a larger
Research Oversight Council; specific types of studies
eligible for funding were defined; the application format
was standardized on the National Institutes of Health (NIH)
model; and biannual submission dates were formalized.
The Research Oversight Council plays a vital role in keeping
the grant program dynamic, as members have the latitude
to create and/or change the direction of the grant funding as
needed. Dr. Miller expanded the council to include the cancer
center’s new external research advisor, Daniel Von Hoff, MD.
Dr. Von Hoff is physician-in-chief and distinguished professor
at The Translational Genomics Research Institute in Phoenix,
Arizona, professor of medicine at Mayo Clinic, and chief
scientific officer for Scottsdale Healthcare and US Oncology
Research. With his extensive experience in the development
of new anticancer agents, Dr. Von Hoff has not only impacted
the enhancement of the grants program at Baylor Sammons
Cancer Center, but has had significant influence on the
development of the new Innovative Clinical Trials Center.
The combination of these two entities allows the latest in
new therapies to be developed and tested more quickly and
efficiently. When Dr. Von Hoff was asked about what contribution he thought the cancer center grant program was
making to Baylor Sammons Cancer Center, he said, “There is
nothing more essential to making substantial advances than
supporting the individual creativity of scientists and clinician
scientists. Often the great need they have is for pilot funding
to use in determining if their idea ‘has legs’ against the
disease. This cancer center grant program is a really special
resource to help these creative investigators in their quest
against the disease.”
Grant Categories Funded by Baylor
Sammons Cancer Center’s Research
Grant Program
Baylor Sammons Cancer Center’s Research Grant Program
is currently funding grants in six categories: pilot project,
gap funding, supplemental funding, trainee cancer research
awards, emerging technology access, and cancer clinical and
translational patient trials. Awards for the first three categories
are limited to a maximum of $150,000 per investigator for a
period not to exceed 24 months. In all six awards, monies
granted are not to be used for principal investigator salaries,
but technician and postdoctoral fellow salary support is
allowed. The number of grants awarded in each category
is determined by the amount of available funding.
Grants are based on core criteria modeled after the typical
NIH format for grant applications. The applicant must address
these questions in the grant proposal:
• What is the significance of the research? Does this study
address an important problem that focuses on translational research? How will scientific knowledge or clinical
practice be advanced?
• What approach is being used by the applicant? Are the
design, methods, and analyses appropriate and adequate
to the aims of the project?
• Is the project original and innovative? Does this study
develop or employ novel concepts, approaches, methodologies, tools, and/or technologies for this area of work?
• Is the work proposed appropriate to the applicant’s level
of experience?
• Does the scientific environment where the work will be
done contribute to the probability of success? Do the
proposed studies benefit from useful collaborative
arrangements, subject populations, or a unique scientific
environment?
• What are the applicant’s prospects for attaining external,
peer-reviewed funding? If the study goals are met, how
likely is it the applicant can compete successfully for
outside grant funding?
Six months after initiation of the study and at 6 month intervals thereafter, the grantee must submit interim reports based
on the specific aims/objectives, describing the progress to
date, any potential or unanticipated problems, and plans to
mitigate such problems. At the end of the award period, the
grantee must submit a final report within 1 month of the end
of the funding period, along with any abstracts, publications,
grants, or clinical trial proposals that have come out of the
completed research. The final report includes the results of
the study as well as an evaluation of the success of the study
in achieving the specific aims. Additionally, it contains the
grantee’s plans for future funding or study continuation. By
using a structured NIH format for the submission process and
for the follow-up reports, the Research Oversight Council can
more easily judge the success of the grant program.
4 Baylor Sammons Cancer Center CancerUpdate
For More Information
The following categories of grants are currently eligible for
funding:
• Pilot Project. Funding is for new projects to generate data
that will support an application for external peer-reviewed
funding. Investigators frequently develop a hypothesis
based on their personal laboratory or clinical experience
and/or information in the literature. However, without data
from preliminary experiments to support the hypothesis, it
is difficult to obtain funding from major granting agencies.
Funding for pilot projects allows the investigator to obtain
the data for proof of concept from small feasibility studies
that will take 1 to 2 years to complete. The investigator
benefits by being able to translate his or her ideas into
concrete evidence to obtain outside funding.
• Gap Funding. This is funding available to investigators with
current peer-reviewed external funding who have applied
for renewal, but have missed the pay line by 20% or less.
The gap funding is the amount needed to continue the
current study until the next review cycle is completed. This
means the investigator can maintain the trained research
team and continue the research while waiting for funding.
• Supplemental Funding. This funding provides additional
monies for current projects that have a shortfall in the
amount necessary to complete the current study goals.
This shortfall could be the result of increased costs after
the grant was funded, an expanded scope of the grant,
or an across-the-board cut in budgets by the granting
agency. This funding is vital so the investigator can successfully compete for external peer-reviewed funding for
an expanded or continued study.
• Trainee Cancer Research Awards Program. New to the
grant program in 2011, awards in this category help to
start young investigators in their research careers. This
grant is open to all residents and fellows in a Baylorapproved postgraduate training program involving the
areas of treatment, diagnosis, and/or etiology of cancer.
Additionally, graduate students working on cancer-related
research in a BRI laboratory with a Baylor investigator as
their primary mentor may apply. Applicants must have a
mentor with demonstrated research experience in the area
of selected study. The proposal must present an original
research study based on sound background and scientific
principles. Applications can be for amounts up to $50,000
for a period of 1 to 2 years. Funding does not cover salary
for the trainee or mentor, but it does include funding for
The biennial dates for submission are normally in spring
(May) and fall (September); however, applications for the
Emerging Technology Access Grants and the Trainee
Cancer Research Awards Program can be submitted at
any time and are not subject to the deadline. For more
details about the program and how to apply, please contact
Grace Rivera in the Office of Clinical Oncology Research
Coordination ([email protected]).
the trainee’s supplies, subject costs, outside tests and
assays, biostatistician consultation, and travel for one
meeting to present data from the research.
• Emerging Technology Access Grants. New to the grant
program in 2012, this award provides funding to cancer
investigators at BRI to give them access to emerging
technologies (e.g., genomics, proteomics, metabolomics)
that are needed for their research and may not be readily
available to them. These studies will be feasibility studies,
and the funding will cover the cost of conducting the
tests in established laboratories, rather than purchasing
expensive technology or equipment to investigate
unproven ideas. The awards are limited to a maximum of
$50,000 per investigator for a period up to 24 months.
• Cancer Clinical and Translational Patient Trials. Another
new grant added to the cancer center grant program this
year is the Clinical and Translational Patient Trials. This
award supports the costs of conducting novel clinical and
translational trials involving human subjects within Baylor.
Funding will primarily be for phase I trials, which screen a
treatment for safety and normally involve 25 or fewer patients, as well as some early phase II trials, which establish
the testing protocol and normally involve up to 40 patients.
Priority will be given to testing agents or methodologies
from BRI laboratories or partner institutions, as well as
clinical trials that include a translational research component. This grant award is up to $500,000 for a period of
up to 30 months. Funding may cover personnel costs for
necessary support personnel (no principal investigator or
coinvestigator costs), patient costs, costs of producing or
obtaining agents for testing, travel to one annual meeting
per year by the principal investigator, and/or biostatistician
consulting costs.
This issue of CancerUpdate will highlight some of the success
stories that have come out of Baylor Sammons Cancer
Center’s Research Grant Program less than 3 years after its
restructuring.
Baylor Sammons Cancer Center CancerUpdate 5
Hope for Advanced Melanoma:
New Developments in Cancer Vaccines
Patients with resected stage IIIc/IV
melanoma have a poor prognosis;
treatment options are limited and
5-year survival rates are less than
30%. Karolina Palucka, MD, PhD,
investigator and Michael A. E. Ramsay
Chair for Cancer Immunology
Research at Baylor Institute for
Immunology Research, has been
Karolina Palucka,
working for over 10 years developing
MD, PhD
and testing vaccines for the treatment
of advanced melanoma. To date,
although a significant proportion of patients have developed
a tumor antigen–specific immune response, only a few have
shown a durable objective tumor regression. Dr. Palucka is
now using funding from Baylor Sammons Cancer Center’s
Research Grant Program to explore a new approach to
Langerhans
cells
Naive
aive
T8
CD8+ T cells
s
Cytotoxic
C
l
lymphocytes
vaccine development that may point the way to more
effective treatment.
Most of the vaccines developed by Dr. Palucka have
involved dendritic cells (DCs), the master controllers of
immune processes in the human body. A key characteristic
of DCs is their plasticity: they will mature differently and have
different capabilities in response to different growth factors
and cytokines. Langerhans cells (LCs), which are found in the
epidermis, prime high-avidity, antigen-specific CD8+ T cells.
These T cells are critical for a long-lived protective immunity
that will prevent relapse in patients with high risk disease.
Interstitial dermal CD14+ DCs, on the other hand, are important in the generation of humoral immunity, including the
production of antibodies and memory B cells. The most
efficient vaccines may be those that target both types of
DCs, allowing stimulation of both cellular and humoral
immune responses.
Dermall
CD14+ DCs
Cs
Plasma
cells
T4
T4
Helper T cells
for CTLs
Helper
T cells
H l
for B cells
T8
T8
Naive
N
B cells
B
B
T8
Granzymes
Perforin
Long-lived memory
CD8+ T cells
B
B
Antibodies
Protection in vivo
Long-lived memory
B cells
Figure 2
Dendritic cell subsets
generate distinct types of
T cell immunity. The most
efficient vaccines may
be those that will target
both Langerhans cells and
dermal CD14+ dendritic
cells, thereby allowing the
maximal stimulation of
cellular and humoral
immune responses and the
generation of long-term
memory protection.
(Figure used by permission
from John Wiley and Sons,
Inc.; K. Palucka, et al,
Dendritic cells and immunity
against cancer, J Int Med,
January 2011, 269(1):64-73.)
6 Baylor Sammons Cancer Center CancerUpdate
“We are in a revolutionary phase in developing immune therapy for cancer. We are seeing some
amazing responses in patients with lung cancer and pancreatic cancer who were classically considered
to be untreatable. We are really entering a new area, where immune therapy will become an everyday
Karolina Palucka, MD, PhD
treatment for cancer.”
For vaccine development, either CD34+ progenitor cells or
monocytes are removed from the patient’s blood by apheresis
and grown in culture with selected growth factors that affect
differentiation and maturation. The resultant DCs are loaded
with tumor-specific antigens before being inoculated back
into the patient. In earlier studies, Dr. Palucka discovered
that monocytes that differentiate into DCs in response to the
cytokine interleukin 4 (IL4) differentiate into interstitial dermal
DCs, whereas treatment with IL15 leads to the generation of
cells with the properties of LCs.
Testing the effectiveness of an IL15 vaccine has posed
several problems. It is a difficult cytokine to produce and has
only recently become available commercially. In addition,
IL15-induced DCs are more fragile than ordinary DCs and
require special handling in the laboratory and clinical settings.
Dr. Palucka has surmounted these difficulties and is now
testing the immunogenicity of IL15 DCs in patients with
advanced melanoma in a pilot study cofunded by Baylor
Sammons Cancer Center’s Research Grant Program and by
National Institutes of Health. The IL15 DCs are loaded with
9 to 10 amino acid peptides derived from four melanoma
antigens. In addition to monitoring vaccine immunogenicity
after 2 weeks, the study will examine progression-free survival and overall survival at 92 weeks.
If the results of this trial are positive, it will furnish another
piece of the puzzle that Dr. Palucka has been putting together
over the last 10 years—how to provide long-lived protective
immunity against a deadly cancer. Dr. Palucka commented:
“We are in a revolutionary phase in developing immune
therapy for cancer. We are seeing some amazing responses
in patients with lung cancer and pancreatic cancer who were
classically considered to be untreatable. We are really entering
a new area, where immune therapy will become an everyday
treatment for cancer.”
Upcoming Meetings of Interest to Oncologists
September 2012
13 2012 Breast Cancer Symposium
September 13–15, 2012
San Francisco, California
http://breastcasym.org
October 2012
3 Association of Community
Cancer Centers National Oncology
Conference
October 3–6, 2012
San Antonio, Texas
http://accc-cancer.org
19 American College of
Gastroenterology Annual Scientific
Meeting
October 19–24, 2012
Las Vegas, Nevada
http://gi.org
25 ASTRO 54th Annual Meeting
October 28-31
Boston, Massachusetts
www.astro.org
Baylor Sammons Cancer Center CancerUpdate 7
One-day Symposia at Baylor Sammons Cancer
Center Provide Updates for Medical Professionals
An important function of Baylor Charles A. Sammons Cancer
Center at Dallas is to serve as a regional center for continuing
medical education for health professionals. This is accomplished by offering day-long symposia that present the latest
information in the prevention, screening, evaluation, and
management of specific cancers. Expert faculty on the
medical staff at Baylor University Medical Center at Dallas
and from other institutions across the country provide
up-to-date presentations as well as one-on-one discussion
time with attendees. Over the last 9 months, two inaugural
symposia have been presented in the areas of lung cancer
and gastrointestinal (GI) cancer.
North Texas Multidisciplinary Lung
Cancer Symposium
The first ever North Texas Multidisciplinary Lung Cancer
Symposium was held on October 1, 2011. This day-long
event centered on recent advances in lung cancer and was
attended by almost 100 residents, fellows, nurses, and physicians from across North Texas, Arkansas, Louisiana, and
Tennessee.
Faculty from across the country presented the latest information on methods of screening, the new TNM staging system
for lung cancer, ways that genetic evaluation can influence
treatment choices, new techniques in minimally invasive surgery, combined modality therapies, integration of biomarkers
for personalized therapy, new paradigms in the treatment
of advanced lung cancer, and the role of maintenance chemotherapy. In addition to the lectures, open discussions led by
a moderator were initiated after each group of talks, allowing
the participants to ask questions of either a particular speaker
or of the panel of speakers. Cases were presented, and an
audience response system was utilized to enhance the
interaction.
GI Surgical Cancer Conference
The inaugural GI Surgical Cancer Conference was held on
February 11, 2012. This event centered on the diagnosis,
treatment, and management of GI cancers and was attended
by 70 medical professionals from across North Texas.
Expert faculty from Baylor lectured on esophageal and
gastric cancers; diseases of the pancreas; and GI malignancy,
genetics, and postoperative care. The keynote speaker was
Herbert Zeh, MD, assistant professor of surgery in the Division
of Surgical Oncology at the University of Pittsburgh, as well as
the codirector of the University of Pittsburgh Cancer Institute
Pancreatic Cancer Center. Dr. Zeh is one of the country’s
leaders in the use of the da Vinci® Surgical System for robotic
pancreatic surgery. This technology allows minimally invasive
surgery that enhances the surgeon’s ability to see details and
allows for more natural movements in performing the Whipple
procedure, one of the most complex surgeries performed to
treat pancreatic cancer. At his institution, this type of robotic
procedure compared to more traditional methods has resulted
in a reduction in blood loss and need for transfusion, shorter
hospital stays, and a faster recovery, reducing the time from
surgery to the start of chemotherapy treatment.
Currently, this technology is being refined at Baylor Dallas
for use in performing distal pancreatectomies. Based on
Dr. Zeh’s experience, it is anticipated that the incorporation
of this procedure will benefit our patients with lower morbidity
and shorter hospital stays.
8 Baylor Sammons Cancer Center CancerUpdate
Focus on Locally Advanced Breast Cancer:
New Insights, New Treatments
Joyce O’Shaughnessy, MD, is Celebrating Women Endowed Chair in Breast Cancer Research
at Baylor Health Care System, cochair of Breast Cancer Research at Texas Oncology and US
Oncology, and a physician on the medical staff at Baylor Dallas. With pilot project funding from
Baylor Sammons Cancer Center’s Research Grant Program, Dr. O’Shaughnessy is investigating
genetic approaches to improve treatment options for women with high-risk breast cancer.
Significant advances have been made
in improving treatment outcomes for
locally advanced breast cancer, using
systemic chemotherapy, endocrine
therapy, and targeted therapy with the
HER2 inhibitor, trastuzumab. However,
aggressive forms of locally advanced
breast cancer, specifically luminal B
breast cancer (high-grade, estrogen
Joyce
receptor [ER]-positive) and tripleO’Shaughnessy, MD
negative breast cancer (TNBC; ER-,
progesterone receptor-, and HER2-negative) are associated
with a higher risk of disease recurrence than low-grade, ERpositive, or HER2-positive disease. Researchers hypothesize
that specific molecular abnormalities are driving these virulent
cancers and that inhibiting these abnormalities will improve
disease outcomes.
Dr. O’Shaughnessy is working with the diagnostic molecular
pathology group in the Department of Pathology at Baylor
University Medical Center at Dallas to molecularly characterize patients with these aggressive breast cancer subtypes.
The goals of the study are to (1) determine the incidence of
key driving mutations associated with these cancers, and
(2) demonstrate the feasibility of molecularly profiling primary
breast cancers in patients who may be candidates for preoperative therapy trials. The study will focus on fibroblast
growth factor receptor-1 (FGFR-1) in luminal B breast
cancers and on the Ras and PI3K pathways in TNBC.
FGFR-1 is amplified in 10% to 15% of ER-positive breast
cancers. This amplification is associated with a poor
prognosis and is believed to drive anchorage-independent
proliferation, a hallmark of oncogenic transformation, and
endocrine therapy resistance. Patients with locally advanced
breast cancer associated with FGFR-1 amplification may
benefit from anti-FGFR-1 agents such as dovitinib, brivanib,
and others.
Because epidermal growth factor receptor (EGFR) is overexpressed in up to 70% of TNBC, the anti-EGFR antibody
cetuximab has been investigated for use as a targeted therapy for this disease. In previous studies, Dr. O’Shaughnessy
and colleagues have shown that 8% to 10% of patients with
TNBC have a durable response to cetuximab. Predicting
who will respond is of key importance, especially since some
patients will derive years of metastatic disease control with
cetuximab. Response may be predicted by downstream factors in the EGFR pathway, including expression of PTEN and
the Ras pathway activator, CRYAB, and activating mutations
in KRAS or PI3K. (See figure on facing page.)
In line with the institution-wide focus on precision medicine,
a high priority of Baylor Sammons Cancer Center’s Breast
Cancer Research Program is to bring innovative new agents
that inhibit driving mutations into neoadjuvant clinical trials
for patients with locally advanced breast cancer. The results
of this trial will demonstrate the feasibility of molecularly
defining patients who will be most likely to benefit in these
trials.
Funding for pilot projects like this by Baylor Sammons
Cancer Center’s Research Grant Program is allowing investigators to explore exciting new directions in breast cancer
research. Dr. O’Shaughnessy commented: “This funding is
incredibly important. It enables us to mount these pilot trials
Baylor Sammons Cancer Center CancerUpdate 9
“You have to be able to generate pilot data in order to take that next step and compete successfully for
Joyce O’Shaughnessy, MD
larger grants or attract pharmaceutical partners for new clinical trials.”
to see if our hypotheses are valid. You have to be able to
generate pilot data in order to take that next step and compete successfully for larger grants or attract pharmaceutical
partners for new clinical trials. You can’t get there
without this pilot funding. It’s how we make progress.”
Downstream Factors in the EGFR Pathway Associated with Breast Carcinogenesis
Growth Factors
Membrane
P
JAK
SRC
PI3K
STAT
Akt
Survival
Proliferation
Oncogenesis
Angiogenesis
Tumorigenesis
Inhibition of Apoptosis
P
PTEN
MKP1
Ras
Raf
MEK
PLCy
DAG
ERK
PKC
Gene Expression
Cell-cycle Progression
Transformation
Differentiation
Apoptosis
10 Baylor Sammons Cancer Center CancerUpdate
Precision Medicine Targets the Prevention
and Treatment of Colorectal Carcinoma
Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second
leading cause of cancer deaths in the United States. In 2011, more than 141,000 new cases
were diagnosed, with an estimated 49,380 people dying of the disease. This bleak prognosis
could be improved at both ends of the disease spectrum: the incidence of new cases could be
reduced, and treatments for existing CRC could be targeted towards the patients who would
be most likely to benefit from them.
Ajay Goel, PhD, director of
epigenetics and cancer prevention
at Baylor Research Institute on the
campus of Baylor University Medical
Center at Dallas, has been working
with C. Richard Boland, MD, chief of
the Division of Gastroenterology at
Baylor Dallas, to understand the complex genetics of CRC. Now, Dr. Goel
is using the knowledge they have
gained to explore new hypotheses in
the prevention and treatment of CRC.
These studies are being funded by
pilot project grants from Baylor
Sammons Cancer Center’s Research
Grant Program.
Ajay Goel, PhD
New Approaches
to Screening for CRC
C. Richard Boland,
CRC develops from the colonic
MD
mucosa in a more or less orderly
fashion, beginning with early changes
from normal to hyperproliferative epithelium, then to the
development of adenomas, which in turn are believed to be
the precursors of carcinomas. These changes are associated
with the accumulation of genetic and epigenetic changes
involving the activation of oncogenes and the inactivation of
tumor suppressor genes.
Because of the directional nature of this progression, one of
the most effective ways to prevent CRC is to find and remove
polyps and other areas of abnormal cell growth before they
develop into malignancies. Colonoscopy is the current gold
standard for screening; it is very accurate at detecting both
malignant and premalignant lesions and permits the removal
of adenomas, thus decreasing cancer incidence. However,
as few as 25% of people older than 50 get colonoscopies
because of concerns about cost, sedation, unpleasant bowel
preparation, and the risk of serious complications. Of those
who do get colonoscopies on a regular schedule, >80% do
not have any important lesions found and could have, in
retrospect, been spared the procedure. What’s needed is, in
effect, a screening test for the screening test.
Adenomas and carcinomas tend to shed abnormal cells from
the colonic lumen. Thus, researchers have been attempting
to develop accurate screening tests based on stool samples
that could be collected at home. Such tests would be noninvasive and inexpensive, removing the major roadblocks to
consumer acceptance of regular colon screening.
Several approaches have been based on the detection of
gene mutations specific to CRC, including APC, TP53, and
KRAS. However, while these tests have provided moderate
diagnostic sensitivity for invasive cancers (50% to 80%), the
sensitivity for advanced benign neoplasms is a somewhat
limited 18% to 40%. Without a high level of sensitivity for
preneoplastic lesions, these tests are not useful for cancer
prevention.
Dr. Goel is now looking at a type of epigenetic marker to
screen for CRC: microRNAs (miRNAs). These short RNA
molecules bind to and inactivate or degrade messenger RNA
Baylor Sammons Cancer Center CancerUpdate 11
(mRNA) transcripts, effectively silencing genes. Each miRNA
may regulate up to several hundred genes. Compared with
DNA and mRNA, which can be technically difficult to adapt
to the clinical setting, miRNAs (perhaps because of their
small size) are resistant to endogenous degradation and thus
are extremely stable. Dr. Goel reports being able to extract
miRNAs with no difficulty from fecal samples archived for over
20 years.
(a)
N
C
A
miR–21
miR–106a
miR–17
miR–143
miR–622
miR–654–3p
10
(b)
*
Epigenetic Clues for Targeting
Treatment in CRC
5
delta Ct-value
*
0
miR–106a
miR–21
-5
-10
Specific patterns of miRNA expression appear to be associated with different cancers. With support from a pilot research
grant awarded in 2010, Dr. Goel has been exploring the
possibility of using miRNA expression profiles in fecal specimens as a surrogate biomarker for the early detection of
CRC. As part of this pilot project, he perfected a technique
for extracting miRNAs from fecal material and has identified
several miRNA markers that he believes will have immense
diagnostic potential for CRC. He was able to demonstrate that
miRNA expression patterns were similar in stool specimens
among healthy volunteers, and reproducible in stool samples
from the same individuals taken at different time points. In 29
patients with CRC, miRNA expression profiles showed higher
expression of miR-21 and miR-106a in patients with adenomas and CRCs compared with controls. Dr. Goel published
a paper describing this work in a premier journal from the
American Association for Cancer Research, Cancer Epidemiology, Biomarkers, & Prevention, where it became one of
the top five most-cited articles in 2010. This work has also
generated several abstracts for presentations at national
meetings, as well as providing preliminary results that form
the backbone of two National Institutes of Health grants.
Patterns of miRNA expression in patients with adenoma and colorectal
cancer (CRC). (a): miRNA expression in patients with adenomatous
polyps (A) and CRC (C) compared with subjects with no endoscopic
abnormalities (N). Plot colors indicate low (green) and high (red) miRNA
expression levels. (b): Quantitative RT-PCR analysis of fecal miRNA
expression between subjects with normal colons (white box plots) and
patients with colorectal neoplasia (gray box plots), showing significantly
increased expression of miR-21 and miR-106a in patients with colon
neoplasms.
(Figure adapted by permission from the American Association for
Cancer Research: A. Link, et al, Fecal microRNAs as novel biomarkers
for colon cancer screening, Cancer Epidemiol Biomarkers Rev, July
2010, 19(7):1766-1774.)
The treatment standard for patients with stage III CRC (lymph
node metastasis but no distant metastasis) calls for adjuvant
chemotherapy after resection. The preferred treatment regimen is FOLFOX, consisting of oxaliplatin, leucovorin, and
5-fluorouracil. Guidelines for patients with stage IV CRC
(with distant metastasis) recommend similar chemotherapy
in combination with targeted drugs such as anti-vascular
endothelial growth factor (VEGF) and anti-epithelial growth
factor receptor (EGFR). All of these adjuvant treatment regimens are associated with potentially serious side effects,
so it is unfortunate that a significant proportion (as many as
50%) of patients who receive these drugs will not derive any
clinical benefit. For some, the disease will progress regardless
of adjuvant therapy, while others would have had no recurrence even without additional treatment. In addition, standard
chemotherapy regimens for CRC last up to 24 weeks, so an
extended period of time passes during which patients are
denied access to alternative drugs that could be more
effective for them. Thus, there is a critical need for biomarkers than can identify which patients will benefit from specific
chemotherapeutic therapies (predictive biomarkers) and
which patients would do well even with no adjuvant treatment
(prognostic biomarkers).
12 Baylor Sammons Cancer Center CancerUpdate
“The discovery of prognostic/predictive biomarkers that can stratify patients with advanced CRC treated
with conventional chemotherapy will open a new era of precision medicine for the management of this
disease.”
Ajay Goel, PhD
There are no predictive/prognostic biomarkers currently
available in the clinical setting except KRAS mutation status,
a marker for anti-EGFR effectiveness in stage IV CRC. Dr.
Goel and his associates will use funding from a new pilot
project grant awarded in January 2012 to systematically
investigate novel predictive/prognostic biomarkers in
advanced CRC based on two types of epigenetic change:
DNA methylation and miRNA expression. Through a collaboration with the Mayo Clinic in Rochester, MN, they have
gained access to a unique and well-characterized collection
of archived tumor samples from a CRC cohort that includes
more than 600 patients with stage III colon cancers treated
with FOLFOX chemotherapy. The results from this pilot
project will provide a springboard for large validation studies
to test the utility of these epigenetic biomarkers for predicting therapeutic outcomes in patients with CRC treated with
standard chemotherapy.
According to Dr. Goel: “The discovery of prognostic/predictive biomarkers that can stratify patients with advanced CRC
treated with conventional chemotherapy will open a new era
of precision medicine for the management of this disease.”
Above: Ajay Goel, PhD, at work in the GI Cancer Research Laboratory
Below: C.Richard Boland, MD, chief of the division of
Gastroenterology at Baylor Dallas, and research lab supervisor
Jennifer Rhees in the lab
Baylor Sammons Cancer Center CancerUpdate 13
Cancer Center Grants for Trainees
and New Investigators
Since Baylor Sammons Cancer Center’s Research Grant
Program was restructured 3 years ago, two trainees and one
new investigator have received grants from the program to
assist in establishing their research careers. In this time of
diminished funding from national sources, these grants from
Baylor Sammons Cancer Center are essential if we want to
produce researchers who can make a significant impact in
the rapidly developing field of biomedical research.
Profiles of Trainees
Baylor Sammons Cancer Center’s Research Grant Program
provides funding to support trainees at the start of their
career. This funding allows them to sample the research
experience to see if it is a direction they might wish to
pursue, as well as providing an appreciation of the research
enterprise that underlies medical progress. Under Dr. Miller’s
leadership, two fellows have received grant funding to date:
Daniel Richey, DO, a former fellow in the nephrology program
at Baylor University Medical Center at Dallas, and Timothy
Zumwalt, PhD candidate in the biomedical studies program
at Baylor University.
Dr. Richey completed his undergraduate studies in biochemistry at Texas
A&M University and received his DO
from the North Texas Health Sciences
Center–Texas College of Osteopathic
Medicine in Fort Worth. He completed
both his internship and residency in
internal medicine at Baylor Dallas
before he started his fellowship in
Daniel Richey, DO
nephrology in the Division of Nephrology, Department of Internal Medicine
at Baylor Dallas. In March 2011, he became the first person to
receive a trainee grant from Baylor Sammons Cancer Center.
Dr. Richey’s study, “Genetic Testing for Focal Segmental
Glomerulosclerosis (FSGS) in Caucasian Women,” was carried out under the mentorship of Andrew Fenves, MD, the
director of the Division of Nephrology and the Ralph Tompsett
Professor of Medicine at Baylor Dallas. FSGS is a common
form of kidney disease in the US. It can lead to nephrotic
syndrome in about 20% of patients, which in turn can lead to
kidney failure. This disease is “focal” in that it causes scarring
of some glomeruli in the kidney while other glomeruli are normal, and it is “segmental” because only part of an individual
glomerulus is damaged. The glomeruli act as filters for the
blood and are responsible for urine production; both functions
are adversely affected by glomerular scarring.
FSGS can be primary, of unknown etiology, or secondary,
the result of known causes such as HIV, hepatitis B virus,
malignancies, or heroin use. The most serious form of secondary FSGS, collapsing FSGS, can rapidly scar the glomeruli,
causing them to “collapse” and result in renal failure. A
number of gene mutations may predispose a patient to
develop FSGS, but the right environment, medication, or
additional gene mutation must be present for it to occur.
One known trigger for collapsing FSGS is use of the drug
pamidronate, a bisphosphonate commonly used to manage
hypercalcemia from malignancies such as multiple myeloma
or breast cancer that has metastasized to the bone. There is
a well-known association between pamidronate therapy and
collapsing FSGS. The purpose of Dr. Richey’s study was to
determine if breast cancer patients who develop collapsing
FSGS in response to treatment with pamidronate have a
genetic predisposition for this complication compared to
patients who receive pamidronate and do not develop collapsing FSGS. The goal was to identify at-risk patients who should
not receive this therapy during the course of any treatment.
Currently, this trial is still ongoing. Dr. Richey has taken a
clinical position outside of Baylor Dallas and assumed a more
peripheral involvement with the study, and Marianna Yager,
MD, a current renal fellow, is now working on finishing the
project with Dr. Fenves. Dr. Richey is still affiliated with Baylor
and plans to use this experience as a springboard to pursue
more clinical research opportunities in his new practice. In
reviewing his experience with program, he commented: “This
is an excellent opportunity for aspiring clinicians in oncology
and oncology-related research.”
Timothy Zumwalt, a PhD candidate in the biomedical studies program at Baylor University, received his undergraduate
degree in molecular and cellular biology from California
14 Baylor Sammons Cancer Center CancerUpdate
Polytechnic State University at San
Luis Obispo. He then worked in the
private sector before deciding to go
to grad-uate school. What sparked
his interest in Baylor University was
the opportunity to do his research
at Baylor Dallas. After completing
his coursework at Baylor University
in Waco, he chose to work with C.
Richard Boland, MD, the chief of the
Timothy Zumwalt
Division of Gastroenterology, Department of Internal Medicine at Baylor Dallas, the head of the
Gastrointestinal Cancer Research Laboratory, and the newly
elected president of the American Gastroenterological Association. Dr. Boland has been studying the genetics of familial
colorectal carcinoma for over 25 years.
With the aid of a trainee grant received in May 2011, Zumwalt
is studying immune involvement in colorectal carcinoma,
specifically the role of the CD4+ helper T cells. Naïve T cells
can differentiate into various lineages, including the Type 1
helper T cells that participate in cellular immunity against
intracellular pathogens and the Type 2 helper T cells that
stimulate or “help” B cells to provide humoral or antibodymediated immunity. Helper T cells are known to inhibit carcinogenesis, with Type 1 cells having strong antitumor activity,
while high expression of Type 2 cells is correlated with tumor
progression and/or recurrence. His objective is to determine
the location of these different helper T cells in the tumor and
correlate the molecular signature of tumors with their helper
T cell population. His overall goal is to understand the
function and the role of these cells in the process of carcinogenesis in the colon.
Zumwalt is working in collaboration with Dr. Boland and with
Karolina Palucka, MD, PhD, investigator and Michael A. E.
Ramsay Chair for Cancer Immunology Research at Baylor
Institute for Immunology Research, as well as gastrointestinal
surgeons on the staff at Baylor Dallas. The surgeons provide
Zumwalt with patient referrals and supply the fresh specimens necessary for his work. He views this trainee grant as
“a wonderful opportunity to conduct medical research.” His
overall goal is to obtain his degree and then continue working
in the field of immunology and cancer research.
Profile of a New Investigator
The Pilot Grant Program is available to new investigators
just starting an independent research program, providing
them with the jump start necessary to
launch a project and collect valuable
pilot data needed to pursue additional
funding. Arianne L. Theiss, PhD, an
associate investigator at Baylor
Research Institute and a member
of the Division of Gastroenterology,
Department of Internal Medicine at
Baylor Dallas, has received a pilot
Arianne L.
grant to study the relationship
Theiss, PhD
between inflammation and cancer
in the gastrointestinal tract. Dr. Theiss started her studies at
Smith College in Massachusetts, where she received her BA
in biology. She then went on to obtain her PhD in cell and
molecular physiology at the University of North Carolina at
Chapel Hill. To further her research career, Dr. Theiss did her
postdoctoral fellowship at Emory University in Atlanta in the
Division of Digestive Diseases in the Department of Medicine
studying the intestinal mucosal pathobiology of colitis. During
her postdoctoral fellowship, Dr. Theiss investigated the role
of prohibitin in colitis. Prohibitin is a ubiquitously expressed
protein that has many roles in basic cell function, including
cell proliferation and programmed cell death. She found that
prohibitin serves as a novel antioxidant and prevents the
changes associated with the inflammatory process that normally occurs during the oxidative stress related to colitis.
Dr. Theiss published a number of studies investigating the
role of prohibitin in colon inflammation during her fellowship.
Dr. Theiss arrived at Baylor Dallas in the fall of 2010 to continue research in the area of inflammation and its association
with colon cancer. She is currently working with Dr. Boland
as well as expanding her own independent research into the
mechanisms of inflammatory bowel disease. Her pilot study
grant, awarded in January 2012, is entitled; “Metabolite
Profiling of Disease Progression in Colitis-Associated Cancer.”
This grant entails studies with the animal model Dr. Theiss
used at Emory University to assess the changes involved in
the progression from the normal colon to colitis and colon
cancer. She is collaborating with members of the Baylor
Kimberly H. Courtwright and Joseph W. Summers Institute
of Metabolic Disease, including Lawrence Sweetman, PhD,
director of the mass spectrometry laboratory, and Raphael
Schiffmann, MD, MHSc, medical director of the Institute of
Metabolic Disease. They are assisting with metabolic profiling of changes that occur as a response to the inflammatory
process. The results of these studies will allow Dr. Theiss to
pursue funding from national agencies to launch an independent research program.
Baylor Sammons Cancer Center CancerUpdate 15
New Clinical Trials at Baylor Charles A.
Sammons Cancer Center at Dallas
Site
Location
Number
Principal investigator
Title
Breast
Texas
10167
Osborne, Cynthia, MD
Oncology
A Randomized, Phase 2 Trial of Preoperative MM-121 with Paclitaxel in HER2-Negative Breast Cancer
Texas
10195
Osborne, Cynthia, MD
Oncology
A Phase 1/2 Dose-Escalation Study of XL147 (SAR245408) or XL765 (SAR245409) in
Combination with Letrozole in Subjects with Hormone Receptor–Positive and HER2Negative Breast Cancer Refractory to a Non-
steroidal Aromatase Inhibitor
Texas
10202
Blum, Joanne L., MD, PhD
Oncology
Phase 1/2, Open-Label, Randomized Study
of the Safety, Efficacy, and Pharmacokinetics
of Letrozole Plus PD 0332991 (Oral CDK 4/6
Inhibitor) and Letrozole Single Agent for the
First-Line Treatment of ER-Positive, HER2Negative Advanced Breast Cancer in Postmenopausal Women
Texas
11086
O’Shaughnessy, Joyce, MD
Oncology
The BEACON Study (Breast Cancer Outcomes with NKTR-102): A Phase 3 Open-Label,
Randomized, Multicenter Study of NKTR102 Versus Treatment of Physician’s Choice in Patients with Locally Recurrent or
Metastatic Breast Cancer Previously Treated
with an Anthracycline, a Taxane and Capecitabine
Texas
11158
Osborne, Cynthia, MD
Oncology
An Open-Label, Multicenter, Randomized, Phase 2 Study Evaluating the Efficacy and
Safety of Ramucirumab (IMC-1121B) Drug Product in Combination with Eribulin Versus Eribulin Monotherapy in Unresectable, Locally
Recurrent or Metastatic Breast Cancer
Patients Previously Treated with Anthracycline and Taxane Therapy
Cancer research studies on the Baylor Dallas campus are conducted through Baylor Research Institute, Texas Oncology, and US Oncology.
Each reviews, approves, and conducts clinical trials independently.
16 Baylor Sammons Cancer Center CancerUpdate
Site
Location
Number
Principal investigator
Title
Texas
11221
O’Shaughnessy, Joyce, MD A Phase II Study of Tesetaxel as Firstline Oncology
Therapy for Subjects with Metastatic Breast Cancer
Breast
Texas
T01115
Blum, Joanne L., MD, PhD
Oncology
A Phase III Randomized, Multicenter, Two-Arm,
Open-Label Trial to Evaluate the Efficacy of Trastuzumab Emtansine Compared with
Treatment of Physician’s Choice in Patients with HER2-Positive Metastatic Breast Cancer Who Have Received at Least Two Prior
Regimens of HER2-Directed Therapy
Chest
Phase 1/2 Study of PX-866 and Docetaxel in Patients with Solid Tumors
Texas
10231
Nadler, Eric, MD
Oncology
Texas
10284
Konduri, Kartik, MD
Oncology
An Open-Label Two-Stage Study of Orally
Administered BKM120 in Patients with
Metastatic Non–Small Cell Lung Cancer with Activated PI3K Pathway
GastrointestinalTexas
11065
Becerra, Carlos R., MD
Oncology
A Randomized Phase 2 Placebo-Controlled Study of LY2495655 in Patients with Advanced
or Metastatic Pancreatic Cancer Receiving
Chemotherapy
Texas
Oncology
Phase 1/2 Study of PX-866 and Cetuximab
11072
Nadler, Eric, MD
Genitourinary
Texas
09217
Hutson, Thomas, DO
Oncology
An Open-Label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and
Efficacy of Docetaxel in Combination with Ramucirumab (IMC-1121B) Drug Product
or IMC-18F1 or Without Investigational Therapy as Second-Line Therapy in Patients with Locally Advanced or Metastatic
Transitional Cell Carcinoma of the Bladder,
Urethra, Ureter, or Renal Pelvis Following
Disease Progression on Firstline Platinum-
Based Therapy
Texas
T01111
Hutson, Thomas, DO
Oncology
An Open-Label, Phase 1/2 Safety, Pharmacokinetic, and Proof-of-Concept Study of ARN-509 in Patients with Progressive
Advanced Castration-Resistant Prostate
Cancer
Baylor Sammons Cancer Center CancerUpdate 17
Site
Location
Number
Principal investigator
Title
Gynecology
Texas
10293
Koon, E. Colin, MD
Oncology
A Phase 3 Randomized, Double-Blind,
Placebo-Controlled, Multicenter Study of AMG 386 with Paclitaxel and Carboplatin as Firstline Treatment of Subjects with FIGO Stage III-IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers
Hematology
Baylor
011-157
Agura, Edward D., MD
Research
Institute
A Phase III Randomized Study of Oral
Sapacitabine in Elderly Patients with Newly
Diagnosed Acute Myeloid Leukemia
Baylor
011-189
Agura, Edward D., MD
Research
Institute
A Phase 2 Study of Brentuximab Vedotin in
Relapsed or Refractory CD30-Positive NonHodgkin Lymphoma
Baylor
011-203
Cooper, Barry, MD
Research
Institute
A Genetic Risk Stratified Randomized Phase II Study of Four Fludarabine/Antibody Combinations for Patients with Symptomatic Previously
Untreated Chronic Lymphocytic Leukemia
Baylor
012-012
Cooper, Barry, MD
Research
Institute
A Phase 2 Study to Evaluate the Safety and
Efficacy of CAL-101 in Patients with Rituximab and Alkylating Agent Refractory Indolent B-Cell Non-Hodgkin Lymphoma
Baylor
012-016
Miller, Alan, MD
Research
Institute
A Randomized Phase II Trial of R-HCVAD/MTX/
Ara-C Induction Followed by Consolidation with an Autologous Stem Cell Transplant vs.
R-Bendamustine Induction Followed by Consolidation with an Autologous Stem Cell
Transplant for Patients ≤65 Years of Age with
Previously Untreated Mantle Cell Lymphoma
Physicians and their patients can now access information about open clinical trials in oncology at Baylor Sammons Cancer
Center by following these steps:
• Go to BaylorHealth.edu/Sammons.
• Click on “Cancer Clinical Trials” on the right-hand menu.
• From the list of studies that appears, click on the study that is of interest to you to view details such as the inclusion/
exclusion criteria.
For additional details or questions about the studies, please contact the Office of Clinical Oncology Research Coordination
at 214.818.8472 or via e-mail at [email protected].
18 Baylor Sammons Cancer Center CancerUpdate
Site
Location
Hematology
Texas
Oncology
Number
10328
Principal investigator
Nadler, Eric, MD
Title
CD30+ Nonlymphoma Malignancies
Texas
11107
Nadler, Eric, MD
Oncology
Screening Protocol to Detect Tumor Antigen
Expression Required for Enrollment on Clinical Research Protocols of Antibody-Directed Therapy
Texas
11197
Miller, Alan, MD
Oncology
A Phase I, Multicenter Open-Label Study to
Evaluate the Pharmacokinetics and Effect of Food of a New Tablet Formulation of Oral
Azacitidine, and to Evaluate the Safety and
Efficacy of Oral Azacitidine in Subjects with
Myelodysplastic Syndromes, Chronic
Myelomonocytic Leukemia and Acute Myeloid Leukemia
Texas
T0926
Becerra, Carlos R., MD
Oncology
Phase I Study of an Autologous Recombinant Idiotype Vaccine Manufactured by magnICON Technology for the Treatment of Patients with Follicular Lymphoma in First Relapse/
Progression
Baylor
011-218
Agura, Edward D., MD
Research
Institute
Carfilzomib Multiple Myeloma Expanded
Access Protocol for Patients with Relapsed and Refractory Disease
Neurology
Baylor
012-009
Fink, Karen, MD, PhD
Research
Institute
Phase II Study of Rindopepimut/GM-CSF in Patients with Relapsed EGFRvIII-Positive
Glioblastoma
Baylor
012-018
Fink, Karen, MD, PhD
Research
Institute
Open-Label Phase 1/2 (Safety Lead-in) Study of Trans Sodium Crocetinate with Concomitant
Treatment of Fractionated Radiation Therapy
and Temozolomide in Newly Diagnosed Glioblastoma Patients to Evaluate Safety and Efficacy
Renal
Texas
T0906
Koon, E. Colin, MD
Oncology
Randomized, Double-Blind Phase 2 Study of Axitinib (AG-013736) with or Without Dose
Titration in Patients with Metastatic Renal Cell Carcinoma
Cancer research studies on the Baylor Dallas campus are conducted through Baylor Research Institute, Texas Oncology, and US Oncology.
Each reviews, approves, and conducts clinical trials independently.
Baylor Sammons Cancer CenterCancer Update 19
Site
Location
Number
Principal investigator
Title
Renal
Texas
T0920
Hutson, Thomas, DO
Oncology
Phase I/II Study of BNC105P in Combination with Everolimus or Following Everolimus for Progressive Metastatic Clear Cell Renal Cell Carcinoma Following Prior Tyrosine Kinase Inhibitors
Skin
Baylor
011-166
Cowey, Charles, MD
Research
Institute
A Phase III Randomized Study of Adjuvant
Ipilimumab Anti-CTLA4 Therapy Versus High-
Dose Interferon a-2b for Resected High-Risk Melanoma
Baylor
011-207
Fay, Joseph W., MD
Research
Institute
Phase II Study to Evaluate the Safety, Tolerability,
and Efficacy of CT-011 Administered Intrave-
nously to Patients with Metastatic Melanoma
Texas
T01008
Cowey, Charles, MD
Oncology
The TEAM Trial (Tasigna Efficacy in Advanced Melanoma): A Randomized, Phase III, Open Label, Multicenter, Two-Arm Study to Compare the Efficacy of Tasigna Versus Dacarbazine in the Treatment of Patients with Metastatic and/or
Inoperable Melanoma Harboring a c-Kit
Mutation
Physicians and their patients can now access information about open clinical trials in oncology at Baylor Sammons Cancer
Center by following these steps:
• Go to BaylorHealth.edu/Sammons.
• Click on “Cancer Clinical Trials” on the right-hand menu.
• From the list of studies that appears, click on the study that is of interest to you to view details such as the inclusion/
exclusion criteria.
For additional details or questions about the studies, please contact the Office of Clinical Oncology Research Coordination
at 214.818.8472 or via e-mail at [email protected].
20 Baylor Sammons Cancer Center CancerUpdate
Site-Specific Tumor Conferences at Baylor
Charles A. Sammons Cancer Center at Dallas
At Baylor Sammons Cancer Center, a key element at the
heart of our approach to patient care and education is
the site-specific tumor conference program. Rather than
focusing solely on recommendations for patient care, the
site-specific conferences also aim at educating the medical professionals attending the conference. Unlike tumor
boards, continuing medical education credit is available for
physicians who attend. Because several patients with the
same diagnosis are presented at each conference, attendees are provided with an in-depth view from specialists,
accompanied by lively discussion.
Conference Schedule:
Bone and Soft Tissue
1st Tuesday
BreastThursdays
Chest
1st, 2nd and 4th Wednesday
Endocrine
3rd Tuesday
Genetics Journal Club/
Case Conference
Mondays
GI
Alternating Thursdays
GynecologyWednesdays
Most of the site-specific tumor conferences have been
relocated to the 10th floor conference center in the new
outpatient cancer center. The gynecology and skull base
conferences currently remain at their former locations.
For more information about the time and location of
site-specific tumor conferences at Baylor Sammons
Cancer Center, please call 214.820.4073.
Head and Neck
2nd and 4th Tuesday
Head and Neck
Journal Club
5th Tuesdays
Hematology/Oncology
Journal Club*
Rotating Wednesdays
Hematology*
Rotating Wednesdays
Liver
2nd Tuesday
Lymphoma*
Rotating Wednesdays
Neuro-oncology
2nd and 4th Wednesday
Pancreas
1st and 3rd Friday
Skin
1st and 3rd Wednesday
Skull Base
1st Wednesday
Stem Cell Transplant*
Rotating Wednesdays
Urology
3rd Wednesday
*Rotate during the month
Baylor Sammons Cancer Center CancerUpdate 21
Recent Publications from Baylor Sammons Cancer Center
November 9, 2011 to March 31, 2012
1. Abair T, O’Shaughnessy J. The clinical
utility of HER2-targeted therapy in the
neoadjuvant setting: recent results from
the San Antonio Breast Cancer Symposium. Clin Breast Cancer 2011;11(1):
15–19.
2. Bracarda S, Hutson TE, Porta C, Figlin
RA, Calvo E, Grünwald V, Ravaud A,
Motzer R, Kim D, Anak O, Panneerselvam A, Escudier B. Everolimus in
metastatic renal cell carcinoma patients
intolerant to previous VEGFr-TKI therapy:
a RECORD-1 subgroup analysis. Br J
Cancer 2012 Mar 22 [Epub ahead of
print].
3. Calvo E, Escudier B, Motzer RJ, Oudard
S, Hutson TE, Porta C, Bracarda S,
Grünwald V, Thompson JA, Ravaud A,
Kim D, Panneerselvam A, Anak O, Figlin
RA. Everolimus in metastatic renal cell
carcinoma: subgroup analysis of patients
with 1 or 2 previous vascular endothelial
growth factor receptor-tyrosine kinase
inhibitor therapies enrolled in the phase
III RECORD-1 study. Eur J Cancer
2012;48(3):333–339.
4. Cao Y, Panos L, Graham RL, Parker
TH 3rd, Mennel R. Primary cutaneous
angiosarcoma of the breast after breast
trauma. Proc (Bayl Univ Med Cent)
2012;25(1):70–72.
5. Choueiri TK, Ross RW, Jacobus S,
Vaishampayan U, Yu EY, Quinn DI, Hahn
NM, Hutson TE, Sonpavde G, Morrissey
SC, Buckle GC, Kim WY, Petrylak DP,
Ryan CW, Eisenberger MA, Mortazavi
A, Bubley GJ, Taplin ME, Rosenberg JE,
Kantoff PW. Double-blind, randomized
trial of docetaxel plus vandetanib versus
docetaxel plus placebo in platinumpretreated metastatic urothelial cancer.
J Clin Oncol 2012;30(5):507–512.
6. Collea RP, Kruter FW, Cantrell JE, George
TK, Kruger S, Favret AM, Lindquist DL,
Melnyk AM, Pluenneke RE, Shao SH,
Crockett MW, Asmar L, O’Shaughnessy
J. Pegylated liposomal doxorubicin plus
carboplatin in patients with metastatic
breast cancer: a phase II study. Ann
Oncol 2012 Mar 19 [Epub ahead of print].
7. Eapen M, Le Rademacher J, Antin JH,
Champlin RE, Carreras J, Fay J, Passweg
JR, Tolar J, Horowitz MM, Marsh JC,
Deeg HJ. Effect of stem cell source on
outcomes after unrelated donor transplantation in severe aplastic anemia.
Blood 2011;118(9):2618–2621.
8. Finkelman BS, Rubinstein WS, Friedman
S, Friebel TM, Dubitsky S, Schonberger
NS, Shoretz R, Singer CF, Blum JL, Tung
N, Olopade OI, Weitzel JN, Lynch HT,
Snyder C, Garber JE, Schildkraut J, Daly
MB, Isaacs C, Pichert G, Neuhausen SL,
Couch FJ, Van’t Veer L, Eeles R, Bancroft
E, Evans DG, Ganz PA, Tomlinson GE,
Narod SA, Matloff E, Domchek S, Rebbeck TR. Breast and ovarian cancer risk
and risk reduction in Jewish BRCA1/2
mutation carriers. J Clin Oncol 2012 Mar
19 [Epub ahead of print].
9. Fleming MT, Sonpavde G, Kolodziej M,
Awasthi S, Hutson TE, Martincic D, Rastogi A, Rousey SR, Weinstein RE, Galsky
MD, Berry WR, Wang Y, Boehm KA,
Asmar L, Rauch MA, Beer TM. Association of rash with outcomes in a randomized phase II trial evaluating cetuximab
in combination with mitoxantrone plus
prednisone after docetaxel for metastatic
castration-resistant prostate cancer. Clin
Genitourin Cancer 2012;10(1):6–14.
10.Garcia M, Choi C, Kim HR, Daoud Y,
Toiyama Y, Takahashi M, Goel A, Boland
CR, Koi M. Association between recurrent
metastasis from stage II and III primary
colorectal tumors and moderate microsatellite instability. Gastroenterology
2012 Mar 27 [Epub ahead of print].
11.Li J, Koike J, Kugoh H, Arita M, Ohhira
T, Kikuchi Y, Funahashi K, Takamatsu
K, Boland CR, Koi M, Hemmi H. Downregulation of MutS homolog 3 by hypoxia
in human colorectal cancer. Biochim
Biophys Acta 2012;1823(4):889–899.
12.Kroeker TR, O’Brien JC. Outcomes of
combined oncologic resection and carotid
endarterectomy in patients with head and
neck cancer. Head Neck 2012 Jan 20
[Epub ahead of print],
13.Motzer RJ, Hutson TE, Olsen MR, Hudes
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Baylor Sammons Cancer Center CancerUpdate 23
Fourth Annual Stone Lectureship Honors
Clinical Research Director of Fred Hutchinson
Cancer Research Center
The fourth annual Marvin J. Stone Lectureship was held at
internal medicine grand rounds on April 10, 2012, in Beasley
Auditorium at Baylor University Medical Center at Dallas. This
year’s recipient was Frederick R. Appelbaum, MD, director
of the Clinical Research Division, Fred Hutchinson Cancer
Research Center, and head of oncology, University of Washington School of Medicine. Dr. Appelbaum is also president
and executive director of the Seattle Cancer Care Alliance,
past chair of the Board of Scientific Advisors of the National
Cancer Institute, and current chair of the Leukemia Committee of the Southwest Oncology Group. Dr. Appelbaum has
authored over 900 scientific publications and was lead author
on the first paper to describe the successful use of autologous bone marrow transplantation in patients with refractory
malignant lymphoma.
At the Lectureship, left to right: Alan M. Miller, MD, PhD, Frederick R.
Appelbaum, MD, Kathy Stone, and Marvin J. Stone, MD, MACP.
Dr. Appelbaum’s presentation was entitled, “The Grand Challenges of Hematopoietic Cell Transplantation.” He described
the progress that has been made in achieving three research
objectives:
1. providing a safe allogeneic donor for every patient;
2. creating a safe and effective preparative regimen for
transplant, and
3. harnessing the “graft versus tumor” effect.
These objectives need to be addressed in order to accomplish
the goal of being able to perform a transplant in any patient.
The Stone Lectureship was instituted in 2009 in honor of
Marvin J. Stone, MD, MACP. Dr. Stone served as chief of
oncology at Baylor Dallas and director of Baylor Sammons
Cancer Center from 1976 to 2008. He currently directs the
medical oncology fellowship program and the internal
medicine clerkship for third-year medical students.
3410 Worth Street
Suite 550
Dallas, Texas 75246
214.820.3535
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PRESORTED
FIRST CLASS
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PERMIT #777
Multiple Myeloma
Research Consortium
Powerful Collaboration Accelerates Results
“Baylor Charles A. Sammons Cancer Center wishes to thank Swim
Across America for their efforts on behalf of our Innovative
Clinical Trials Center. On June 9, 250 swimmers participated
in the event at Lake Ray Hubbard in Rockwall, Texas. Over
the last two years, Swim Across America has raised over
$635,000 that directly benefits our Phase I clinical trials
program, bringing the latest in treatment options to patients
with cancer.”
Alan M. Miller, MD, PhD