Talazoparib for the Treatment of Advanced Solid Tumors and Deleterious BRCA Mutations
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This pilot phase I / II trial studies the action and how well talazoparib works in treating patients with deleterious BRCA mutations and solid tumors that have spread to other places in the body (advanced) 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.
- 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 metastatic disease must have received at least one line of standard of care (SOC) treatment for metastatic disease prior to enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of greater than 3 months
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin =< 1.5 x institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
- Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min for patients with creatinine levels above institutional normal
- The effects of talazoparib (BMN 673) on the developing human fetus are unknown; for this reason and because PARP inhibitors are known to be teratogenic, 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 talazoparib (BMN 673) administration
- 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
- Ability to understand and the willingness to sign a written informed consent document
- 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
- 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 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
- Patients who are receiving any other investigational agents
- 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
- 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
- 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
- Pregnant women are excluded from this study because the effects of the study drugs on the developing fetus are unknown
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with talazoparib (BMN 673); in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- 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
Locations & Contacts
Trial Objectives and Outline
I. Determine the pharmacodynamic effect of talazoparib (BMN 673) in tumor biopsies from patients with advanced ovarian, breast, or other solid tumor and deleterious breast cancer (BRCA) mutations.
I. Determine the response rate (complete response [CR] + partial response [PR]) of treatment with talazoparib (BMN 673) in patients with deleterious BRCA mutations.
Patients receive talazoparib orally (PO) on days 1-28. Cycles 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.
Trial Phase & Type
NCI - Center for Cancer Research
A P Chen
Secondary IDs 14-C-0015, NCI-2013-02371, P131220, 09-25-0099, 14-C-0015, 140015, P9510_A08PAMDREVW01
Clinicaltrials.gov ID NCT01989546