A Study of Rebastinib (DCC-2036) in Combination With Carboplatin in Patients With Advanced or Metastatic Solid Tumors
- Conditions
- Locally Advanced or Metastatic Solid Tumor
- Interventions
- Registration Number
- NCT03717415
- Lead Sponsor
- Deciphera Pharmaceuticals, LLC
- Brief Summary
This is an open-label Phase 1b/2 multicenter study of rebastinib (DCC-2036) in combination with carboplatin designed to evaluate the safety, tolerability, and pharmacokinetics (PK) in participants with advanced or metastatic solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 70
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Male or female patients ≥18 years of age at the time of informed consent.
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Part 1 (Dose Escalation). Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which carboplatin is considered appropriate treatment.
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Part 2 (Dose Expansion)
- Previously treated, triple-negative breast cancer.
- Recurrent platinum-sensitive ovarian cancer.
- Histologically confirmed pleural or peritoneal malignant mesothelioma.
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ECOG performance status of ≤2.
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Able to provide an archival tumor tissue sample.
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Adequate organ function and bone marrow reserve.
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If a female of childbearing potential, must have a negative pregnancy test prior to enrollment.
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Patient must provide signed consent to participate in the study and is willing to comply with study-specific procedures.
- Received prior anticancer or other investigational therapy within 28 days or 5× the half-life (whichever is shorter) prior to the first dose.
- Not recovered from prior-treatment toxicities to Grade ≤1 or baseline.
- Peripheral neuropathy of any etiology >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.
- Symptomatic 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 Rebastinib Dose escalation with rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC6 at Day 1 of each 21-day cycle. Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5 Rebastinib Dose expansion in triple-negative breast cancer (TNBC) participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 Rebastinib Dose escalation with rebastinib 50 milligram (mg) twice daily (BID) orally (PO) in 21-day cycles in combination with carboplatin administered by intravenous (IV) infusion at area under the curve (AUC)5 at Day 1 of each 21-day cycle. Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 Rebastinib Dose escalation with rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5 Rebastinib Dose expansion in TNBC participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5 Rebastinib Dose expansion in platinum-sensitive ovarian cancer participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5 Rebastinib Dose expansion in platinum-sensitive ovarian cancer participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5 Rebastinib Dose expansion in mesothelioma participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5 Rebastinib Dose expansion in mesothelioma participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5 Carboplatin Dose escalation with rebastinib 50 milligram (mg) twice daily (BID) orally (PO) in 21-day cycles in combination with carboplatin administered by intravenous (IV) infusion at area under the curve (AUC)5 at Day 1 of each 21-day cycle. Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5 Carboplatin Dose escalation with rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6 Carboplatin Dose escalation with rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC6 at Day 1 of each 21-day cycle. Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5 Carboplatin Dose expansion in triple-negative breast cancer (TNBC) participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5 Carboplatin Dose expansion in TNBC participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5 Carboplatin Dose expansion in platinum-sensitive ovarian cancer participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5 Carboplatin Dose expansion in platinum-sensitive ovarian cancer participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5 Carboplatin Dose expansion in mesothelioma participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle. Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5 Carboplatin Dose expansion in mesothelioma participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events Baseline up to 2.32 years Number of participants who experienced serious adverse events (SAE) and adverse events (AE).
Objective Response Rate (ORR) (Dose Expansion Phase) Time from CR or PR to disease progression or death due to any cause (Up to 1.53 years) Percentage of participants who achieved an objective response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 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 including baseline; or the appearance of one or more new lesions.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) (Dose Escalation Phase) Time from CR or PR to disease progression or death due to any cause (Up to 1.53 years) Percentage of participants who achieved an objective response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 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 including baseline; or the appearance of one or more new lesions.
Duration of Response (DOR) Time from PR or CR to PD or Death due to Any Cause (up to 1.53 years) Time from first partial response (PR) or complete response (CR) to disease progression (PD) or death due to any cause. Evaluation of radiographic disease assessment per Response Evaluation Criteria in Solid Tumor (RECIST v1.1). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 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 including baseline; or the appearance of one or more new lesions.
Time to Progression (TTP) First Dose of Study Drug to PD (Up to 1.63 years) Time from first dose of study drug to the first documentation of progressive disease (PD). Participants were considered to have progressive disease if they had documented progression based on radiologic assessment according to RECIST v1.1. RECIST v1.1 defined disease progression as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions.
Progression-free-survival (PFS) First Dose of Study Drug to PD or Death due to Any Cause (up to 1.63 years) Time from first dose of study drug to disease progression (PD) or death due to any cause. Participants who undergo surgical resection of target or non-target lesions, who have received other anticancer treatments, including surgical resection or radiation (other than palliative radiation to pre-existing bone metastases'), or who do not have a documented date of progression or death due to any cause will be censored at the date of the last assessment. Disease progression per RECIST v1.1 is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Overall Survival (OS) Baseline to death due to any cause (Up to 2.12 years) Time from baseline C1 D1 to date of death due to any cause. Participants who are still alive or who are lost to follow-up will be censored at the date of last contact.
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 Days) Cmax of rebastinib
PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1) Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 Days) Measure the AUC 0-3 hours
Trial Locations
- Locations (9)
The Ohio State University
🇺🇸Columbus, Ohio, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of California San Francisco (UCSF)
🇺🇸San Francisco, California, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
UCLA Medical Center
🇺🇸Santa Monica, California, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States