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

NCT ID: NCT03601897

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 177 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-25
• Study Completion Date: 2022-05-23

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.

Conditions

Locally Advanced or Metastatic Solid Tumor

Keywords

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

Dose escalation of rebastinib 50 milligram (mg) twice daily (BID) orally (PO) in combination with paclitaxel administered by intravenous (IV) infusion at 80 mg/meter squared (m\^2) on days 1, 8, and 15 of repeated 28-day cycles.

Group Type: EXPERIMENTAL

Rebastinib

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2

Dose escalation of rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Group Type: EXPERIMENTAL

Rebastinib

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

Dose expansion in triple-negative breast cancer (TNBC). Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Group Type: EXPERIMENTAL

Rebastinib

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2

Dose expansion in TNBC. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Group Type: EXPERIMENTAL

Rebastinib

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

Dose expansion in inflammatory breast cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Group Type: EXPERIMENTAL

Rebastinib

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2

Dose expansion in inflammatory breast cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Group Type: EXPERIMENTAL

Rebastinib

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

Dose expansion in ovarian cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 repeated 28-day cycles.

Group Type: EXPERIMENTAL

Rebastinib

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2

Dose expansion in ovarian cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Group Type: EXPERIMENTAL

Rebastinib

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

Dose expansion in endometrial cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Group Type: EXPERIMENTAL

Rebastinib

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2

Dose expansion in endometrial cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Group Type: EXPERIMENTAL

Rebastinib

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

Dose expansion in gynecological carcinosarcoma (GCS). Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Group Type: EXPERIMENTAL

Rebastinib

Intervention Type: DRUG

Administered orally

Paclitaxel

Intervention Type: DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Interventions

Rebastinib

Administered orally

Intervention Type: DRUG

Paclitaxel

Paclitaxel administered by IV infusion at 80 mg/m\^2

Intervention Type: DRUG

Other Intervention Names

DCC-2036

Eligibility 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. Eastern Cooperative Oncology Group Performance Status (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 central nervous system (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. QT interval corrected by Fridericia's formula (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. Human immunodeficiency virus (HIV) or hepatitis C (HCV) infection only if taking medications excluded per protocol, active hepatitis B (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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deciphera Pharmaceuticals, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, United States

University of Colorado Denver- Anschutz Medical Center

Aurora, Colorado, United States

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

The University of Kansas Clinical Research Center

Kansas City, Kansas, United States

Dana-Farber

Boston, Massachusetts, United States

Northwell Health/Monter Cancer Center

Lake Success, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Women & Infants Hospital

Providence, Rhode Island, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Oncology Consultants- Texas Medical Center

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

DCC-2036-01-003

Identifier Type: -

Identifier Source: org_study_id