An Open Label, Multicenter, Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Carboplatin to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 70
- 试验地点
- 9
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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, triple-negative breast cancer.
- •Recurrent platinum-sensitive ovarian cancer.
- •Histologically confirmed pleural or peritoneal malignant mesothelioma.
- •ECOG performance status of ≤
- •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.
排除标准
- •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
- •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
- •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.
研究组 & 干预措施
Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5
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.
干预措施: Carboplatin (Drug)
Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5
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.
干预措施: Rebastinib (Drug)
Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5
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.
干预措施: Rebastinib (Drug)
Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5
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.
干预措施: Carboplatin (Drug)
Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5
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.
干预措施: Rebastinib (Drug)
Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5
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.
干预措施: Carboplatin (Drug)
Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5
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.
干预措施: Rebastinib (Drug)
Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5
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.
干预措施: Carboplatin (Drug)
Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5
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.
干预措施: Rebastinib (Drug)
Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5
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.
干预措施: Carboplatin (Drug)
Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6
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.
干预措施: Rebastinib (Drug)
Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6
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.
干预措施: Carboplatin (Drug)
Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5
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.
干预措施: Rebastinib (Drug)
Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5
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.
干预措施: Carboplatin (Drug)
Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5
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.
干预措施: Rebastinib (Drug)
Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5
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.
干预措施: Carboplatin (Drug)
Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5
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.
干预措施: Rebastinib (Drug)
Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5
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.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: 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)
时间窗: 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.
次要结局
- 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))
- Duration of Response (DOR)(Time from PR or CR to PD or Death due to Any Cause (up to 1.53 years))
- Time to Progression (TTP)(First Dose of Study Drug to PD (Up to 1.63 years))
- Progression-free-survival (PFS)(First Dose of Study Drug to PD or Death due to Any Cause (up to 1.63 years))
- Overall Survival (OS)(Baseline to death due to any cause (Up to 2.12 years))
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1)(Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 Days))
- 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))