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

Deciphera Pharmaceuticals, LLC

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Locally Advanced or Metastatic Solid Tumor

Treatments: Drug: Rebastinib; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT03601897

DCC-2036-01-003

Details and patient eligibility

About

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.

Enrollment: 177 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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177 participants in 11 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Rebastinib

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Rebastinib

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Rebastinib

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Rebastinib

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Rebastinib

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Rebastinib

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Rebastinib

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Rebastinib

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Rebastinib

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Rebastinib

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Rebastinib