PARP inhibitor BMN-673 in Treating Patients with Advanced Solid Tumors and BRCA Mutations
Basic Trial Information
|Phase II, Phase I||Biomarker/Laboratory analysis, Treatment||18 and over||14-C-0015|
NCI-2013-02371, 09-25-0099, 140015, P131220, P9510_A08PAMDREVW01, 9510, NCT01989546
This pilot phase I/II trial studies poly (adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP) inhibitor BMN-673 (talazoparib) in treating patients with breast cancer (BRCA) mutations and solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Further Study Information
I. Determine the pharmacodynamic effect of BMN 673 (talazoparib) in tumor biopsies from patients with advanced ovarian, breast, or other solid tumor and deleterious BRCA mutations.
I. Determine the response rate (complete response [CR] + partial response [PR]) of treatment with BMN 673 in patients with advanced ovarian or primary peritoneal carcinoma and deleterious BRCA mutations.
II. Determine the response rate (CR + PR) of treatment with BMN 673 in patients with advanced breast carcinoma and deleterious BRCA mutations.
III. Determine the response rate (CR + PR) of treatment with BMN 673 in patients with advanced solid tumor (other than breast or ovarian) and deleterious BRCA mutations.
Patients receive talazoparib orally (PO) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Adult patients with documented deleterious BRCA 1 or 2 mutations with histologically confirmed ovarian, primary peritoneal, breast, prostate, pancreas, gastric or other solid tumor whose disease has progressed following at least one standard therapy or who have no acceptable standard treatment options; patients with ovarian cancer should have one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents or extended therapy administered after surgical or non-surgical assessment; ovarian cancer patients with both platinum-sensitive and platinum-resistant disease are eligible; patients with platinum-refractory disease are NOT eligible; definitions:
Platinum sensitive ovarian cancer is defined as patients who respond to platinum-based therapy (complete or partial) and then progress/recur more than 6 months after their last platinum dose (i.e., platinum-free interval is > 6 months)
Platinum resistant ovarian cancer is defined as patients who respond to platinum-based therapy (complete or partial) and then progress/recur within 6 months of their last platinum dose (i.e., platinum-free interval is =< 6 months)
Platinum refractory ovarian cancer is defined as patients who have progression of disease while receiving platinum-based chemotherapy or who fail to achieve at least a partial response to platinum-based chemotherapy (i.e., best response to platinum-based chemotherapy is stable disease)
Patients with prostate cancer can continue to receive treatment with gonadotropin-releasing hormone (GnRH) agonists while on study, as long as there is evidence of disease progression on therapy
Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer or ovarian cancer should have received at least two lines of systemic therapy in the advanced setting
Ability to understand and the willingness to sign a written informed consent document
Patients must be able to swallow whole tablets or capsules; nasogastric or gastrostomy (G)-tube administration is not allowed; any gastrointestinal disease which would impair ability to swallow, retain, or absorb drug is not allowed
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after completing study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 3 months after completion of BMN 673 administration
Creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional upper limit of normal
Total bilirubin =< 1.5 X institutional upper limit of normal
Platelets >= 100,000/mcL
Absolute neutrophil count >= 1,500/mcL
Leukocytes >= 3,000/mcL
Life expectancy of greater than 3 months
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Patients with metastatic disease must have received at least one line of standard of care (SOC) treatment for metastatic disease prior to enrollment
Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded; low molecular weight heparin is permitted for prophylactic or therapeutic use; low-dose warfarin (< 1 mg/day) is permitted
Women who are currently lactating
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Pregnant women are excluded from this study
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Eligibility of subjects receiving any medications or substances with the potential to affect the activity or pharmacokinetics of BMN 673 will be determined following review by the principal investigator
Patients with known active brain metastases or carcinomatous meningitis are excluded from this clinical trial; patients whose brain metastatic disease status has remained stable for >= 4 weeks following treatment of brain metastases are eligible to participate at the discretion of the principal investigator
Patients who are receiving any other investigational agents
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients who have had prior treatment with any PARP inhibitors are ineligible
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
National Cancer Institute
- National Cancer Institute
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01989546
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.