A Study of Rebastinib (DCC-2036) in Combination With Carboplatin in Patients With Advanced or Metastatic Solid Tumors
Published: November 30, 2018
Primary Outcome Measures
- Adverse Events (Part 1 and Part 2) [Time Frame: Approximately 24 months]
- Objective response rate (ORR) (Part 2) [Time Frame: Approximately 24 months]
Secondary Outcome Measures
- Maximum observed concentration (Cmax) of rebastinib [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (each cycle is 21 days) ]
Measure the Cmax
- Area under the concentration-time curve (AUC) of rebastinib [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (each cycle is 21 days) ]
Measure the AUC
- Progression-free-survival (PFS) [ Time Frame: Approximately 24 months ]
Measure of the time from Cycle 1 Day 1 to disease progression or death due to any cause
- Time to progression (TTP) [ Time Frame: Approximately 24 months ]
Measure of the time from Cycle 1 Day 1 to the first documentation of progressive disease
- Duration of response (DOR) [ Time Frame: Approximately 24 months ]
Measure of time from PR, CR to disease progression or death due to any cause
- Overall survival (OS) [ Time Frame: Approximately 24 months ]
Measure of overall survival
- Inclusion Criteria
- Male or female patients ≥18 years of age at the time of informed consent.
- Part 1 (Dose Escalation) Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which carboplatin is considered appropriate treatment.
- Part 2 (Dose Expansion)
- Previously treated, metastatic breast cancer.
- Recurrent ovarian cancer.
- Histologically confirmed pleural or peritoneal malignant mesothelioma
- ECOG PS of ≤2.
- Able to provide an archival tumor tissue sample
- Adequate organ function and bone marrow reserve
- If a female of childbearing potential, must have a negative pregnancy test prior to enrollment.
- Patient must provide signed consent to participate in the study and is willing to comply with study-specific procedures.
- Exclusion Criteria
- Received prior anticancer or other investigational therapy within 14 days or 5× the half-life (within 28 days for biologics) prior to the first dose.
- Not recovered from prior-treatment toxicities to Grade ≤1.
- Concurrent malignancy.
- Known active CNS metastases.
- Use of systemic corticosteroids.
- Known retinal neovascularization, macular edema or macular degeneration.
- History or presence of clinically relevant cardiovascular abnormalities.
- QTcF >450 ms in males or >470 ms in females.
- Left ventricular ejection fraction (LVEF) <50% at screening.
- Arterial thrombotic or embolic events.
- Venous thrombotic event.
- Active infection ≥Grade 3.
- Known HIV or HCV infection only if taking medications excluded per protocol, active HBV, or active HCV infection.
- Use of proton pump inhibitors.
- If female, the patient is pregnant or lactating.
- Major surgery 4 weeks prior to the first dose of study drug
- Malabsorption syndrome or other illness which could affect oral absorption.
- Known allergy or hypersensitivity to any component of rebastinib or any of its excipients.
- Any other clinically significant comorbidities