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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver- Anschutz Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Clinical Research Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Lake Success, New York, United States, 11042
      • Northwell Health/Monter Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women & Infants Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Oncology Consultants- Texas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 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 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: rebastinib; 25 mg tablets or 75 mg tablets; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m2
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	Drug: rebastinib; 25 mg tablets or 75 mg tablets; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Deciphera Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2018
• Primary Completion (Actual): May 23, 2022
• Study Completion (Actual): May 23, 2022

Study Registration Dates

• First Submitted: July 5, 2018
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 18, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: breast cancer; endometrial cancer; paclitaxel; ovarian cancer; rebastinib; gynecological carcinosarcoma; malignant mixed Mullerian tumor (MMMT)
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; Rebastinib
• Other Study ID Numbers: DCC-2036-01-003

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