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

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

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.

Study Overview

• Status: Completed
• Conditions: Locally Advanced or Metastatic Solid Tumor
• Intervention / Treatment: Drug: rebastinib; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • University of California San Francisco (UCSF)
    • Santa Monica, California, United States, 90404
      • UCLA Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78240
      • Next Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients ≥18 years of age at the time of informed consent.
2. Part 1 (Dose Escalation). Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which carboplatin is considered appropriate treatment.

3. Part 2 (Dose Expansion)

   • Previously treated, triple-negative breast cancer.
   • Recurrent platinum-sensitive ovarian cancer.
   • Histologically confirmed pleural or peritoneal malignant mesothelioma.
4. ECOG performance status 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 (whichever is shorter) prior to the first dose.
2. Not recovered from prior-treatment toxicities to Grade ≤1 or baseline.
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. Symptomatic venous thrombotic event.
13. Active infection ≥Grade 3.
14. Known 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; 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; 25 mg tablets or 75 mg tablets; Other Names: DCC-2036; Drug: Carboplatin; Carboplatin administered by IV infusion at AUC5 or AUC6
Experimental: Part 2; 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; 25 mg tablets or 75 mg tablets; Other Names: DCC-2036; Drug: Carboplatin; Carboplatin administered by IV infusion at AUC5 or AUC6

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Deciphera Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2019
• Primary Completion (Actual): May 1, 2022
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: October 19, 2018
• First Submitted That Met QC Criteria: October 22, 2018
• First Posted (Actual): October 24, 2018

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; mesothelioma; ovarian cancer; rebastinib
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Carboplatin; Rebastinib
• Other Study ID Numbers: DCC-2036-01-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No