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

• ClinicalTrials.gov Identifier: NCT03601897
• Recruitment Status: Active, not recruiting
• First Posted: July 26, 2018
• Last Update Posted: September 30, 2021
• Sponsor: Deciphera Pharmaceuticals LLC
• Information provided by (Responsible Party): Deciphera Pharmaceuticals LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Locally Advanced or Metastatic Solid Tumor	Drug: rebastinib; Drug: Paclitaxel	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 201 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 19, 2018
• Estimated Primary Completion Date: October 1, 2022
• Estimated Study Completion Date: October 1, 2022

Arms and Interventions

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 Name: 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 Name: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m2

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Maximum observed concentration (Cmax) of rebastinib [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 (each cycle is 28 days) ]
   Measure the Cmax
2. 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
3. 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
4. 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
5. Duration of response (DOR) [ Time Frame: Approximately 36 months ]
   Measure of time from PR, CR to disease progression or death due to any cause
6. Overall survival (OS) [ Time Frame: Approximately 36 months ]
   Measure of overall survival

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, United States, 35233

United States, Colorado

University of Colorado Denver- Anschutz Medical Center

Aurora, Colorado, United States, 80045

United States, Illinois

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States, 60611

United States, Kansas

The University of Kansas Clinical Research Center

Kansas City, Kansas, United States, 66160

United States, Massachusetts

Dana-Farber

Boston, Massachusetts, United States, 02215

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

Northwell Health/Monter Cancer Center

Lake Success, New York, United States, 11042

United States, Ohio

Ohio State University Wexner Medical Center

Columbus, Ohio, United States, 43210

United States, Oklahoma

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

United States, Rhode Island

Women & Infants Hospital

Providence, Rhode Island, United States, 02905

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Oncology Consultants- Texas Medical Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Deciphera Pharmaceuticals LLC

More Information

• Responsible Party: Deciphera Pharmaceuticals LLC
• ClinicalTrials.gov Identifier: NCT03601897
• Other Study ID Numbers: DCC-2036-01-003
• First Posted: July 26, 2018
• Last Update Posted: September 30, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Deciphera Pharmaceuticals LLC:

rebastinib; paclitaxel; breast cancer; ovarian cancer; endometrial cancer; gynecological carcinosarcoma; malignant mixed Mullerian tumor (MMMT)

Additional relevant MeSH terms:

Neoplasms; Paclitaxel; Rebastinib; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Protein Kinase Inhibitors; Enzyme Inhibitors