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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 1, 2022

Interventions

  • Drug: rebastinib
    • 25 mg tablets or 75 mg tablets
  • Drug: Paclitaxel
    • Paclitaxel administered by IV infusion at 80 mg/m2

Arms, Groups and Cohorts

  • Experimental: Part 1 – Completed
    • 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.
  • Experimental: Part 2
    • 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

Clinical Trial Outcome Measures

Primary Measures

  • Adverse Events (Part 1 and Part 2)
    • Time Frame: Approximately 36 months
  • Objective response rate (ORR) (Part 2)
    • Time Frame: Approximately 36 months

Secondary Measures

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

Participating in This Clinical Trial

Inclusion Criteria

1. Male or female patients ≥18 years of age at the time of informed consent. 2. Part 1 Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which paclitaxel is considered appropriate treatment. 3. 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 4. ECOG PS of ≤2. 5. Able to provide an archival tumor tissue sample 6. Adequate organ function and bone marrow reserve 7. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment. 8. Patient must provide signed consent to participate in the study and is willing to comply with study-specific procedures. Exclusion Criteria:

1. Received prior anticancer or other investigational therapy within 28 days or 5× the half-life prior to the first dose. 2. Not recovered from prior-treatment toxicities to Grade ≤1. 3. Peripheral neuropathy of any etiology >Grade 1. 4. Concurrent malignancy. 5. Known active CNS metastases. 6. Use of systemic corticosteroids. 7. Known retinal neovascularization, macular edema or macular degeneration. 8. History or presence of clinically relevant cardiovascular abnormalities. 9. QTcF >450 ms in males or >470 ms in females. 10. Left ventricular ejection fraction (LVEF) <50% at screening. 11. Arterial thrombotic or embolic events. 12. Venous thrombotic event. 13. Active infection ≥Grade 3. 14. HIV or HCV infection only if taking medications excluded per protocol, active HBV, or active HCV infection. 15. Use of proton pump inhibitors. 16. If female, the patient is pregnant or lactating. 17. Major surgery 4 weeks prior to the first dose of study drug 18. Malabsorption syndrome or other illness which could affect oral absorption. 19. Known allergy or hypersensitivity to any component of rebastinib or any of its excipients. 20. Any other clinically significant comorbidities

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Deciphera Pharmaceuticals LLC
  • Provider of Information About this Clinical Study
    • Sponsor

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.