Evaluation of Talazoparib, a PARP Inhibitor, in Patients With Somatic BRCA Mutant Metastatic Breast Cancer: Genotyping Based Clinical Trial
Overview
- Phase
- Phase 2
- Intervention
- Talazoparib
- Conditions
- Breast Cancer
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 30
- Locations
- 7
- Primary Endpoint
- Median Progression Free Survival
- Status
- Recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
This research is to evaluate the effectiveness of Talazoparib as a potential treatment for metastatic breast cancer with a BRCA 1 or BRCA 2 mutation.
Detailed Description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved talazoparib for the participants' specific disease but it has been approved for metastatic breast cancer with a germline (inherited) BRCA mutation. Talazoparib is a study drug that inhibits (stops) the normal activity of certain proteins called "poly (ADP-ribose) polymerases" also called "PARPs". PARPs are proteins (made from genes which are part of your DNA) that are found in all normal and cancer cells that are involved in the repair of DNA. PARPs are needed to repair mistakes that can happen in DNA when cells divide. If the mistakes are not repaired, the defective cell will usually die and be replaced. Cells with mistakes in their DNA that do not die can become cancer cells. Cancer cells may be killed by a study drug, like talazoparib, that stops the normal activity of PARPs. In clinical trials, the use of talazoparib and other PARP inhibitors have shown that these drugs can reduce tumor size and slow tumor growth in some cancer patients with BRCA1 or BRCA2 mutations. In this research study, the investigators are examining how effective talazoparib is in patients with metastatic breast cancer with a BRCA mutation in their tumor.
Investigators
Neelima Vidula
Principal Investigator
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Metastatic breast cancer with deleterious somatic BRCA 1 or 2 mutations detectable by cell-free circulating tumor DNA, by CLIA certified clinical assay (including but not restricted to MGH-Snapshot cfDNA assay, Guardant360, Foundation One). The eligibility of a given assay and/or BRCA mutation could be discussed with the primary investigator (Dr. Vidula) and senior investigator (Dr. Bardia), who will provide the final discretion.
- •Patients with germline BRCA 1 or 2 mutations will not be eligible.
- •Patients with only a VUS (Variant of Unknown Significance), or non-functional BRCA mutation, without a deleterious somatic BRCA 1 or 2 mutation will not be eligible.
- •The following disease subtypes are eligible:
- •Triple negative breast cancer (defined as ER \< 1%, PR \< 1%, HER2 negative, as per ASCO CAP guidelines), with disease progression on at least one prior chemotherapy regimen in the metastatic setting.
- •Hormone receptor positive, HER2 negative disease with disease progression on at least one prior endocrine therapy in the metastatic setting or be considered inappropriate for endocrine therapy
- •Patients must have evaluable or measurable disease.
- •Any number of prior lines of therapy are allowed
- •Patients may have received prior platinum based chemotherapy (0-1 prior platinum based therapy). However, the patient must not have progressed while on platinum treatment (any setting), or within 6 months after end of treatment (neoadjuvant and/or adjuvant).
- •At least two weeks from last systemic therapy for breast cancer, with recovery of all treatment related toxicity to grade 1 or less. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion.
Exclusion Criteria
- •Treatment with an investigational agent within 4 weeks of the first dose of treatment.
- •Patients must not have received prior treatment with a PARP inhibitor
- •Patients must not have a germline BRCA 1 or 2 mutation
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion.
- •-If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- •Has known, untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 7 months after the last dose of trial treatment.
Arms & Interventions
Talazoparib
-Talazoparib will be provided as capsules for oral administration daily
Intervention: Talazoparib
Outcomes
Primary Outcomes
Median Progression Free Survival
Time Frame: From the start of treatment until death or disease progression, up to approximately 2 years
Progression-Free Survival (PFS) is defined as the time from the first dose of study treatment to the date of disease progression as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death due to any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of 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 new lesions is also considered progression).
Secondary Outcomes
- Objective Response Rate(From the start of treatment until treatment discontinuation, up to approximately 2 years)
- Number of Participants with Treatment-related Serious Adverse Events(From the start of treatment until treatment discontinuation, up to approximately 2 years)