Download Title A Phase II Study of the PARP Inhibitor, BSI

Title
A Phase II Study of the PARP Inhibitor, BSI-201, in Combination with Chemotherapy to Treat Triple
Negative Breast Cancer Brain Metastasis
Purpose of the Study
Nearly half of patients with advanced Triple Negative Breast cancer
(BM). Triple Negative Breast Cancer (TNBC) lacks the three types
cancer growth-estrogen (ER), progesterone (PR), and HER2/neu.
determine how well the treatment with Irinotecan(chemotherapy) plus
how safe it is for TNBC that has spread to the brain.
(TNBC) develop brain metastases
of receptors known to fuel breast
The purpose of this study is to
Iniparib(PARP Inhibitor) works and
Sponsor
BiPAR Sciences and Sanofi-Aventis
Participating Sites
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Dana-Farber/ Harvard Cancer Center
Duke University Medical Cancer Center
Georgetown University Lombard Cancer Center
Indiana University Simon Cancer Center
Johns Hopkins University
MD Anderson Cancer Center
University of Alabama, Birmingham
University of California, San Francisco
University of Chicago Medical Center
University of Michigan Comprehensive Cancer Center
University of North Carolina, Chapel Hill
University of Pittsburgh Cancer Institute
Vanderbilt University
Start Date & Stop Date
Date First Site Activated: July, 2010
Date Trial Closed to Accrual: August, 2012
Key Eligibility Requirements
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Triple Negative Breast Cancer with brain metastasis measuring greater than 5 mm on Magnetic
Resonance Imaging (MRI).
No limit to number of prior systemic therapies (use drugs that spread throughout the body to treat
cancer cells wherever they may be).
Stable or decreasing dose of steroids for greater than or equal to 7 days.
Must be at least 21 years old
ECOG performance status less than 2 (ambulatory and capable of all self care but unable to carry
out any work activities; up and about more than 50% of waking hours)
Life expectancy of greater than or equal to 12 weeks.
Have adequate organ function, no serious infection or other chronic or acute diseases.
Must not be pregnant or breast-feeding.
Must not have had a previous allergic reaction to Iniparib or Irinotecan
Patients with intracranial hemorrhage, impending herniation or diffuse leptomeningeal disease
were excluded.
Use of a class of drugs, CYP3A4 inhibitors (except systemic glucocorticoids) was prohibited.
Study Design
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Eligible patients had TNBC with new or progressive brain metastasis and received Irinotecan and
Iniparib every 3 weeks.
Primary Endpoint – Time to progression.
Secondary Endpoints - response rate, clinical benefit rate, overall survival, toxicity, and healthrelated quality of life
Correlative Endpoints - molecular subtyping and gene expression studies on pre-treatment
archival tissues, and determination of germline BRCA1/2 status.
Results
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Thirty-seven patients began treatment with iniparib and irinotecan;
o Thirty-four were able to be evaluated for effectiveness.
o Five of thirty-four patients were known to carry a BRCA germline mutation (four with
BRCA1, one withBRCA2).
o Mean age was 48 years
Median time to progression was 2.14 months.
Median overall survival was 7.8 months.
Intracranial response rate was 12% (four of thirty-four patients) while intracranial clinical benefit
rate was 27% (nine of thirty four patients).
Treatment was well tolerated.
o The most common moderate to severe- adverse events were neutropenia (14%) and
fatigue (5%).
o Diarrhea was common (54%), but moderate to severe - diarrhea was rare (3%).
Intrinsic subtyping revealed 19 of 21 tumors (79%) were basal-like, and intracranial response was
associated with high expression of proliferation-related genes.
This study suggests a modest benefit of Irinotecan plus Iniparib in progressive triple negative
breast cancer brain metastases.
Next Steps
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In addition to illustrating modest efficacy and general tolerability of combination of Irinotecan and
Iniparib in the setting of progressive triple negative breast cancer (TNBC) brain metastases, this
study illustrated feasibility of enrolling patients into clinical trials with this aggressive disease.
The completion of TBCRC 018 laid the foundation for future studies evaluating novel agents for
this treatment-resistant disease.
o As an example, investigators from both Alliance and SWOG are working together to
initiate a randomized clinical trial of cisplatin/placebo vs. cisplatin/ABT-888 (veliparib) in
patients with advanced TNBC (SWOG1416); this study includes a brain metastases
cohort. Many of the TBCRC investigators will be taking part in this study through their
affiliations with SWOG and Alliance, and will have experience enrolling patients with
TNBC brain metastases as a result of their participation in TBCRC 018.
Scientific Publications Available for this Clinical Trial
Anders, C.K., Nanda, R., Liu, M.C., Blackwell, K.L., Van Poznak, C.H., Abramson, V.G., Storniolo,
A.M., Lin, N.U., Stearns, V., Melhem, A., Puhalla, S., Carpenter, J.T., Melisko, M.E., Deal, A.M.,
Hudis, C., Winer, E.P., Perou, C.M., Bradley, C.R., Wolff, A.C., Carey, L.A. TBCRC 018: Phase II study
of iniparib plus chemotherapy to treat triple-negative breast cancer (TNBC) brain metastases (BM). 2011
ASCO, Trials in Progress Poster TPS127.
Anders, C., Deal, A., Abramson, V., Liu, M., Storniolo, A.M., Carpenter, J.T., Puhalla, S., Nanda, R.,
Melhem-Bertrandt, A., Lin , N.U., Marcom, P.K., Van Poznak, C., Stearns, V., Melisko, M., Smith, J.K.,
Karginova, O., Winer, E.P., Perou, C.M., Wolff, A.C., Carey, L.A. TBCRC 018: Phase II study of iniparib
plus chemotherapy to treat triple negative breast cancer (TNBC) central nervous system (CNS)
metastases (mets). 2013 ASCO, Poster Discussion Session, Abstract #515.
Anders, C., Deal, A.M., Abramson, V., Liu, M.C., Storniolo, A.M., Carpenter, J.T., Puhalla, S., Nanda, R.,
Melhem-Bertrandt, A., Lin, N.U., Marcom, P.K., Van Poznak, C., Stearns, V., Melisko, M., Smith, J.K.,
Karginova, O., Parker, J., Berg, J., Winer, E.P., Peterman, A., Pratt, A., Perou, C.M., Wolff, A.C., Carey,
L.A. TBCRC 018: Phase II study of iniparib in combination with irinotecan to treat progressive triple
negative breast cancer brain metastases. Breast Cancer Res Treat 146 (3): 2014.
Link to the NCI Summary on ClinicalTrials.gov
NCT01173497
*This summary was reviewed by: Carey K. Anders, M.D. This summary was also reviewed and approved by the members of the
TBCRC Patient Advocate Working Group.