Study of BMN-673 With Carboplatin and Paclitaxel in Patients With Advanced BRCA-mutated Solid Tumor or Triple Negative Metastatic Breast Cancer

NCT02358200 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 14955
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Open label, non-randomized, dose escalation and expansion Phase Ia/b trial to evaluate the safety of the combination of BMN 673 and carboplatin, and subsequently BMN 673 in combination with paclitaxel and carboplatin to determine the recommended Phase II dose of the combination.

Conditions

Triple Negative Metastatic Breast Cancer; BRCA-mutated Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Response rate of combination (BMN 673 + carboplatin) in patients with BRCA germline mutations or triple negative cancer without known BRCA mutations, in solid tumor malignancies with paclitaxel with a 15 patient cohort expansion at the maximum tolerated dose (MTD). Response and progression in this study will be evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.

  From date of randomization until the date of Initial response to the first documented tumor progression or date of death from any cause, up to 18 months.

Secondary Outcomes (1)

• Intolerable Toxicity

  From first dose to 30 day follow up.

Study Arms (1)

Treatment

EXPERIMENTAL

BMN-673: Oral, every day, Days 1-21; Carboplatin: intravenous, every week, 750 μg/day; Paclitaxel: intravenous, every week, 0.75 x Maximum Tolerated Dose μg/day

Drug: BMN-673; Drug: Carboplatin; Drug: Paclitaxel

Interventions

BMN-673 DRUG

Treatment

Carboplatin DRUG

Treatment

Paclitaxel DRUG

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, 18 years or older with advanced malignancies for which no standard therapy is available.
• Dose Escalation: Patients with any solid tumor malignancies
• Does Expansion:
• Patients with advanced malignancies that have germline and/or somatic BRCA mutations (cohort gBRCA) Or
• Triple negative (TN) metastatic breast cancer without known BRCA mutation (cohort TNBC). Tumors will be considered TN when:
• Estrogen receptor (ER) expression \<1%
• Progesterone receptor (PR) expression \<1%
• Her2 negative as per the American Society of Clinical Oncology (ASCO) guidelines
• Paclitaxel expansion: any solid tumor malignancy with potential benefit from this combination and paclitaxel (ASP).
• Consent to screening tumor biopsy (for accessible tumors when appropriate) \[optional in dose escalation, mandatory in dose expansion\]
• Part 2 only: Measureable tumor (RECIST1.1)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
• Adequate organ function:
• Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
• Hemoglobin (Hgb) ≥9.5 g/dL(transfusion before treatment is allowable if more than 3 days prior to study start)

You may not qualify if:

• Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks, whichever is shorter, prior to starting study treatment
• Patients must have recovered from side effects from prior cancer-directed therapy to grade 1 or less (unless deemed not clinically significant by study investigator).
• Major surgery ≤ 4 weeks prior to starting study regimen or who have not recovered from surgery.
• Any known unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure.
• History of myocardial infraction (MI) within 6 month prior to starting study treatment.
• Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Any condition that confounds the ability to interpret data from the study.
• Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 4 weeks are allowed.
• Malabsorption or uncontrolled peptic ulcer disease
• Grade 2 or higher peripheral neuropathy (paclitaxel arm only)
• Known allergic reaction or poor tolerability to PARP inhibitors, carboplatin, or paclitaxel
• Pregnant or breastfeeding
• Known active human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV)

Sponsors & Collaborators

• Pamela Munster: lead
• QuantumLeap Healthcare Collaborative: collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94115, United States

Location

MeSH Terms

Interventions

talazoparib; Carboplatin; Paclitaxel

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Pamela Munster, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor in Residence

Study Record Dates

• First Submitted: January 27, 2015
• First Posted: February 6, 2015
• Study Start: February 23, 2015
• Primary Completion: January 8, 2019
• Study Completion: January 8, 2019
• Last Updated: January 10, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)