A Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Paclitaxel in Patients With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This is an open-label Phase 1b/2 multicenter study of rebastinib (DCC-2036) in combination with paclitaxel designed to evaluate the safety, tolerability, and pharmacokinetics (PK) in patients with advanced or metastatic solid tumors.

Official Title
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An Open-Label, Multicenter, Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Paclitaxel to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced or Metastatic Solid Tumors

Conditions
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Locally Advanced or Metastatic Solid Tumor

Intervention / Treatment
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* Drug: rebastinib
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients ≥18 years of age at the time of informed consent. Part 1 Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which paclitaxel is considered appropriate treatment. Part 2 Triple-negative and Stage IV inflammatory breast cancer. Recurrent ovarian cancer. Recurrent, metastatic or high-risk endometrial cancer. Advanced (stage III or IV), or recurrent gynecological carcinosarcoma Homologous or heterologous type carcinosarcoma (malignant mixed Mullerian tumor [MMMT] allowed 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 28 days or 5× the half-life prior to the first dose. Not recovered from prior-treatment toxicities to Grade ≤1. 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. Venous thrombotic event. Active infection ≥Grade 3. 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
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 - Completed<br>Dose comparison between 50 or 100 mg BID of rebastinib orally (PO) in combination with paclitaxel administered by IV infusion at 80 mg/m2 in repeated 28-day cycles. | Drug: rebastinib<br>* 25 mg tablets or 75 mg tablets<br>* Other names: DCC-2036;Drug: Paclitaxel<br>* Paclitaxel administered by IV infusion at 80 mg/m2<br>|
| Experimental: Part 2<br>Dose expansion in the following tumor types at the recommended Phase 2 dose (RP2D) of rebastinib in combination with paclitaxel Triple-negative and Stage IV inflammatory breast cancer Ovarian cancer Endometrial cancer Gynecological Carcinosarcoma | Drug: rebastinib<br>* 25 mg tablets or 75 mg tablets<br>* Other names: DCC-2036;Drug: Paclitaxel<br>* Paclitaxel administered by IV infusion at 80 mg/m2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (Part 1 and Part 2) |  | Approximately 36 months | 
| Objective response rate (ORR) (Part 2) |  | Approximately 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) of rebastinib | Measure the Cmax | Cycle 1 Day 1, Cycle 1 Day 15 (each cycle is 28 days) | 
| Area under the concentration-time curve (AUC) of rebastinib | Measure the AUC | Cycle 1 Day 1, Cycle 1 Day 15 (each cycle is 28 days) | 
| Progression-free-survival (PFS) | Measure of the time from Cycle 1 Day 1 to disease progression or death due to any cause | Approximately 36 months | 
| Time to progression (TTP) | Measure of the time from Cycle 1 Day 1 to the first documentation of progressive disease | Approximately 36 months | 
| Duration of response (DOR) | Measure of time from PR, CR to disease progression or death due to any cause | Approximately 36 months | 
| Overall survival (OS) | Measure of overall survival | Approximately 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rebastinib, paclitaxel, breast cancer, ovarian cancer, endometrial cancer, gynecological carcinosarcoma, malignant mixed Mullerian tumor (MMMT)