BMN 673 (Talazoparib), an Oral PARP Inhibitor, in People With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment
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|ClinicalTrials.gov Identifier: NCT02326844|
Recruitment Status : Terminated (Study was closed by the Cancer Therapy Evaluation Program (CTEP))
First Posted : December 30, 2014
Results First Posted : May 24, 2017
Last Update Posted : August 27, 2018
- The new drug BMN 673 (talazoparib) has been shown to fight tumor cells in animals and some people. It is a poly (ADP-ribose) polymerase (PARP) inhibitor. It works on tumor cell deoxyribonucleic acid (DNA) damage repair process. Researchers want to see if BMN 673 shrinks cancer again in women with ovarian cancer and whose cancer initially got shrunk but grew back on the first PARP inhibitor.
- To study BMN 673 (talazoparib) in people with ovarian cancer born with a breast cancer (BRCA) mutation and whose cancer got shrunk but became worse after they took a similar drug.
- Women at least 18 years old:
- with recurrent and/or metastatic germline breast cancer mutation (gBRCAm)-associated ovarian cancer AND
- whose disease is growing after already being treated with PARP inhibitors AND
- with no other treatment(s) in between the first PARP inhibitors and a screening visit.
- Participants will be screened with medical history, physical exam, and heart and blood tests.
- Participants will take the study drug by mouth once daily. They will take the drug in 28-day cycles.
- They will keep a diary of doses and any side effects.
- Participants will have 4 study visits in cycle 1, then 1 visit every cycle. Visits may include:
- Blood tests
- Physical exam
- Computed tomography (CT) or magnetic resonance imaging (MRI) scans. Participants will lie in a machine that takes pictures of their body.
- Participants will have a biopsy before starting the study drug. A small piece of tumor tissue will be removed by needle, guided by a scan. They may have two more biopsies later.
- Participants will be followed for 30 days after taking the last dose of study drug. A physical exam, blood tests, and CT or other scans will be done.
- Participants will have follow-up calls to ask about any side effects.
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer||Drug: BMN 673 (talazoparib)||Phase 2|
- Patients with germline BRCA1/2 mutations (gBRCAm) demonstrate repeated therapeutic susceptibility to deoxyribonucleic acid (DNA) damaging agents, especially platinums, even if they have previously progressed on a similar (platinum-based) regimen.
- Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have clinical activity in gBRCAm-associated malignancies, although patients eventually develop progressive disease.
- BMN 673 (talazoparib) is a novel PARPi, with excellent oral bioavailability and greater anti-tumor activity in vitro and in vivo at lower concentrations than first generation PARPi.
- It is unknown whether secondary BRCA mutations or other potential mechanisms of clinical resistance portend cross-resistance to a highly potent PARPi.
-To determine the objective response rate (complete response (CR)+partial response (PR)) of single agent BMN 673 (talazoparib) in ovarian cancer patients with gBRCAm who have progressed on prior PARPi therapy.
- Women with recurrent and/or metastatic gBRCAm-associated ovarian cancer, with progression on PARPi monotherapy within the immediate prior 2 months of the time of screening visit.
- Patients should have responded to their prior PARPi therapy (CR, PR or stable disease (SD)>4months).
- Patients cannot have received another therapy between stopping their first PARPi therapy\ and initiating therapy on this trial, but must be off the prior PARPi for at least 4 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and adequate organ and marrow function.
- This is an open label, single arm phase II trial to examine activity of BMN 673 (talazoparib).
- Patients will receive BMN 673 (talazoparib) at the recommended phase 2 dose (RP2D) of 1mg p.o. once daily on 28 day cycles.
- Research samples including whole blood, plasma, circulating tumor cells (CTCs), and tumor biopsies will be obtained for progressive disease (PD) endpoints at baseline, cycle 1 day 29 (prior to cycle 2 day 1), and/or at progression in all patients.
- Patients will be evaluated every two cycles for response using Response Evaluation Criteria in Solid Tumors (RECIST)v1.1 criteria and every cycle for safety using Common Terminology Criteria in Adverse Events (CTCAE)v4.0.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Pilot Study of BMN 673 (Talazoparib), an Oral PARP Inhibitor, in Patients With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment|
|Actual Study Start Date :||March 2, 2015|
|Actual Primary Completion Date :||April 14, 2016|
|Actual Study Completion Date :||April 14, 2016|
Experimental: Ovarian Cancer Patients
Ovarian cancer patients with germline breast cancer mutation (gBRCAm) who have progressed on prior poly (ADP-ribose) polymerase inhibitor (PARPi) therapy
Drug: BMN 673 (talazoparib)
1 mg by mouth (p.o.) once daily on 28-day cycles until disease progression
- Objective Response (Complete Response (CR) + Partial Response (PR)) [ Time Frame: Every 2 cycles, an average of 64 days ]Objective response (complete response (CR) + partial response (PR)) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
- Number of Participants With Serious and Non-serious Adverse Events [ Time Frame: 15 months ]Here is the number participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events v4.0. For a detailed list of events, see the adverse event module.
- Duration of Response [ Time Frame: 3 months ]Duration of response is the time between study enrollment and off-treatment date.
- Progression Free Survival (PFS) on BMN673 (Talazoparib) to PFS From First Poly (ADP-ribose) Polymerase Inhibitor (PARPPi) Exposure [ Time Frame: 3 months ]The median time to progression after receiving BMN673 will be compared informally to the time of progression for the same patients after receiving an initial PARPi exposure. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more lesions is also considered progressions).
- Forkhead Box 03 (FOXO3a), p53-binding Protein 1 (53BP1) and RAD51 (i.e., Eukaryote Gene) Biomarkers [ Time Frame: Baseline ]Patients will undergo a mandatory biopsy at baseline and reverse phase protein microarray (RPPA)26 testing will be performed to determine the potential predictive biomarkers of subsequent poly (adenosine diphosphate [ADP]) ribose polymerase inhibitors (PARPi ) response.
- Secondary Mutation of Breast Cancer 1 (BRCA1) and Breast Cancer 2 (BRCA2) [ Time Frame: Baseline ]Patients will undergo a mandatory biopsy at baseline and Next Generation Sequencing to elucidate the secondary mutations of BRCA1 and BRCA2 will be performed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02326844
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Jung-Min Lee, M.D.||National Cancer Institute (NCI)|