Download Breast Cancer: A phase III randomized, double blind placebo

Breast Cancer:
A phase III randomized, double blind placebo controlled
study of BKM120 with fulvestrant, in postmenopausal
women with hormone receptor-positive HER2-negative
locally advanced or metastatic breast cancer which
progressed on or after aromatase inhibitor treatment
5.2 Inclusion criteria
Patients eligible for inclusion in this study have to meet all of the
following criteria:
2. Patient has histologically and/or cytologically confirmed diagnosis of
breast cancer
3. Patient has adequate tumor tissue (either archival tumor tissue or new
tumor biopsy) for
the analysis of PI3K-related biomarkers (PIK3CA mutation, PTEN expression).
One
tumor block (preferred) or a minimum of 20 unstained slides is recommended
to
determine the PI3K activation status. Enrollment in the study will be
contingent to the
central laboratory confirming reception of adequate amount of tissue
including sufficient
DNA for analysis.
Note: Patients with previously documented PI3K pathway results by a
Novartis
designated laboratory and/or who have confirmation of adequate tumor tissue
to perform
all protocol required procedures (e.g. bridging study) are eligible. This
may include
patients who are being re-screened or coming from another Novartis study.
4. Patient has inoperable locally advanced or metastatic breast cancer
5. Patient has HER2 negative breast cancer (based on most recently analyzed
biopsy) defined
as a negative in situ hybridization by approved test or an IHC status of 0,
1+ or 2+ (if IHC
2+, a negative in situ hybridization test is required) by local laboratory
testing
6. Patient has ER positive and/or PgR positive breast cancer by local
laboratory testing
(based on most recently analyzed biopsy)
7. Patient is postmenopausal.
8. Patient has disease refractory to AI defined as:
Recurrence while on, or within 12 months of end of adjuvant treatment
with AI, or
Progression while on, or within one month of end of AI treatment for
locally advanced
or MBC
Note: AI do not have to be the last treatment prior to enrollment in the
run-in
treatment phase. Patients who received maximum one prior chemotherapy line
for
MBC are allowed. Other prior anticancer therapies, e.g. tamoxifen are also
allowed.
Patients do not need to meet the definition of “refractory to AI” within
any specified
time period prior to enrollment in the run-in treatment phase. Patients can
receive any
number of endocrine/hormonal lines of therapy before or after meeting the
definition
of “refractory to AI”.
13. Patient has an Eastern Cooperative Oncology Group (ECOG) performance
status ≤ 2
which the investigator believes is stable at the time of screening
Pancreatic Cancer
GAP Study: Phase II study of Gemcitabine and nab-Paclitaxel for Resectable Pancreas
Cancer.
The Australasian Gastro-Intestinal Trials Group (AGITG) Protocol No: AG0111PS
3.2 Inclusion criteria
1. Males or females with histologically or cytologically confirmed adenocarcinoma or poorly
differentiated carcinoma of the pancreas. In those patients with histology or cytology highly
suspicious for adenocarcinoma, the diagnosis of pancreatic adenocarcinoma will be made by
integrating this histological data with the clinical and radiographic data (tumour mass visible on
three phase CT scan (or MRI scan) of the pancreas). Patients with islet cell neoplasms are
excluded;
2. Disease is clearly resectable on the basis of physical examination and the following objective
CT criteria (or MRI if indicated):
(i) no evidence of extra-pancreatic disease;
(ii) no evidence of tumour abutment of the superior mesenteric artery (SMA) or coeliac axis
(T4); and
(iii) no evidence of portal vein infiltration of more than 180°of the circumference or occlusion of
the superior mesenteric vein (SMV) or SMV–portal vein (PTV) confluence.
3. Age >18 yrs.
4. ECOG performance status 0 – 2, with a life expectancy of ≥ 3 months.
5. Adequate renal, hepatic and haematological function. Adequate hepatic function for this trial
is defined as:
a. Bilirubin <1.5 X ULN (Upper Limit of Normal), AST + ALT <3.0 X ULN. In patients who have
had a recent biliary drainage and whose bilirubin is descending, a value of 3 X N (50 μmoles/L)
is acceptable.
Colorectal Cancer
Assessment of Overall Survival of FOLFOX6m plus
SIR-Spheres microspheres versus FOLFOX6m alone as
first-line treatment in patients with non-resectable liver
metastases from primary colorectal carcinoma in a randomised
clinical study
Inclusion Criteria:
 Histologically confirmed adenocarcinoma of the colon or rectum, with or without primary
tumour in situ.
 Unequivocal and measurable CT evidence of liver metastases which are not treatable by
surgical resection or local ablation with curative intent at the time of study entry.
 Limited extra-hepatic metastases in the lung and/or lymph nodes are permitted. Metastases in
the lung must either be not more than five nodules in number with no nodule more than 1 cm in
diameter or one single lesion of up to 1.7 cm in diameter. Involvement of lymph nodes in one
single anatomic region (pelvis, abdomen or chest) is permitted provided their longest diameter
measures less than 2 cm.
 All imaging evidence used as part of the screening process must be within 28 days prior to the
time of randomisation.
 Suitable for either treatment regimen and study procedures as determined by clinical
assessment undertaken by the Investigator.
 Prior chemotherapy for metastatic colorectal cancer is not allowed. Patients may have received
adjuvant chemotherapy or (neo-) adjuvant chemo-radiotherapy to the pelvis, provided the last
dose of chemotherapy was administered at least 6 months prior to entry into this study.
Radiotherapy to the pelvis is not an exclusion criterion.
Melanoma
BRIM8: A Study of Vemurafenib Adjuvant Therapy in Patients With
Resected Cutaneous BRAF Mutant Melanoma
This multi-center, randomized, double-blind, placebo-controlled study will evaluate the efficacy
and safety of vemurafenib in patients with completely resected, cutaneous BRAF-mutation
positive melanoma at high risk for recurrence. Patients will be randomized to receive oral doses
of vemurafenib 960 mg twice daily or matching placebo. The anticipated time on study treatment
is 52 weeks.
Inclusion Criteria:
•
Patients with completely resected, histologically confirmed, Stage IIC or Stage III,
cutaneous melanoma where the BRAFV600 mutation status of the current primary tumor or
involved lymph node is determined to be positive using the cobas® BRAF V600 Mutation Test.
Patients with Stage IIIA disease must have at least one lymph node metastasis measuring > 1
mm in diameter
•
Patients must have been surgically rendered free of disease within 70 days of
randomization
•
Eastern Cooperative Oncology Group performance status of 0 or 1
•
Life expectancy of at least 5 years
•
Patients must have fully recovered from the effects of any major surgery or significant
traumatic injury prior to the first dose of study treatment
•
Adequate hematologic, hepatic and renal function
A Phase III randomized, 3-arm, open label, multicenter
study of LGX818 plus MEK162 and LGX818 monotherapy
compared with vemurafenib in patients with unresectable
or metastatic BRAF V600 mutant melanoma
Patients eligible for inclusion in this study have to meet all of the
following criteria:
1. Signed written informed consent;
2. Male or female patient, age ≥ 18 years;
3. Histologically confirmed diagnosis of locally advanced, unresectable or
metastatic
cutaneous melanoma AJCC Stage IIIB, IIIC or IV (Appendix 1);
4. Presence of BRAF V600E or V600K mutation in tumor tissue prior to
enrollment, as
determined by a Novartis designated central laboratory(ies);
5. Naïve untreated patient for unresectable locally advanced or metastatic
melanoma;
Note: Prior adjuvant therapy is permitted (e.g. IFN, IL-2 therapy, any
other
immunotherapy or radiotherapy).
6. Evidence of at least one measurable lesion as detected by radiological
or photographic
methods according to Novartis guideline version 3.1 based on RECIST version
1.1;
Note: A previously irradiated lesion is eligible to be considered as a
measurable lesion
provided that there is objective evidence of progression of the lesion
since discontinuation
of therapy and prior to starting study drug.