A Study of Rebastinib (DCC-2036) in Combination With Carboplatin in Patients With Advanced or Metastatic Solid Tumors

Study Overview
=================
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 patients with advanced or metastatic solid tumors.

Official Title
-----------------
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

Conditions
-----------------
Locally Advanced or Metastatic Solid Tumor

Intervention / Treatment
-----------------
* Drug: rebastinib
* Drug: Carboplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
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, triple-negative breast cancer. Recurrent platinum-sensitive ovarian cancer. Histologically confirmed pleural or peritoneal malignant mesothelioma. ECOG performance status 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 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Dose comparison between 50 or 100 mg BID of rebastinib orally (PO) dosed in 21-day cycles in combination with carboplatin administered by IV infusion at either AUC5 or AUC6 once every 3 weeks | Drug: rebastinib<br>* 25 mg tablets or 75 mg tablets<br>* Other names: DCC-2036;Drug: Carboplatin<br>* Carboplatin administered by IV infusion at AUC5 or AUC6<br>|
| Experimental: Part 2<br>Dose expansion in the following tumor types at the recommended Phase 2 dose (RP2D) of rebastinib in combination with carboplatin Triple-negative breast cancer Platinum-sensitive Ovarian cancer Mesothelioma | Drug: rebastinib<br>* 25 mg tablets or 75 mg tablets<br>* Other names: DCC-2036;Drug: Carboplatin<br>* Carboplatin administered by IV infusion at AUC5 or AUC6<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (Part 1 and Part 2) |  | Approximately 24 months | 
| Objective response rate (ORR) (Part 2) |  | Approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) of rebastinib | Measure the Cmax | Cycle 1 Day 1, Cycle 2 Day 1 (each cycle is 21 days) | 
| Area under the concentration-time curve (AUC) of rebastinib | Measure the AUC | Cycle 1 Day 1, Cycle 2 Day 1 (each cycle is 21 days) | 
| Progression-free-survival (PFS) | Measure of the time from Cycle 1 Day 1 to disease progression or death due to any cause | Approximately 24 months | 
| Time to progression (TTP) | Measure of the time from Cycle 1 Day 1 to the first documentation of progressive disease | Approximately 24 months | 
| Duration of response (DOR) | Measure of time from first PR, CR to disease progression or death due to any cause | Approximately 24 months | 
| Overall survival (OS) | Measure of the interval between Cycle 1 Day 1 until date of death from any cause | Approximately 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
rebastinib, mesothelioma, breast cancer, ovarian cancer