A Study of Rebastinib (DCC-2036) in Combination With Carboplatin 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: Carboplatin; Drug: Rebastinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03717415

DCC-2036-01-004

Details and patient eligibility

About

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 participants with advanced or metastatic solid tumors.

Enrollment: 70 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 (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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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70 participants in 9 patient groups

Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5

Experimental group

Description:

Dose escalation with rebastinib 50 milligram (mg) twice daily (BID) orally (PO) in 21-day cycles in combination with carboplatin administered by intravenous (IV) infusion at area under the curve (AUC)5 at Day 1 of each 21-day cycle.

Treatment:

Drug: Rebastinib

Drug: Carboplatin

Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5

Experimental group

Description:

Dose escalation with rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle.

Treatment:

Drug: Rebastinib

Drug: Carboplatin

Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6

Experimental group

Description:

Dose escalation with rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC6 at Day 1 of each 21-day cycle.

Treatment:

Drug: Rebastinib

Drug: Carboplatin

Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5

Experimental group

Description:

Dose expansion in triple-negative breast cancer (TNBC) participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle.

Treatment:

Drug: Rebastinib

Drug: Carboplatin

Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5

Experimental group

Description:

Dose expansion in TNBC participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle.

Treatment:

Drug: Rebastinib

Drug: Carboplatin

Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5

Experimental group

Description:

Dose expansion in platinum-sensitive ovarian cancer participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle.

Treatment:

Drug: Rebastinib

Drug: Carboplatin

Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5

Experimental group

Description:

Dose expansion in platinum-sensitive ovarian cancer participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle.

Treatment:

Drug: Rebastinib

Drug: Carboplatin

Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5

Experimental group

Description:

Dose expansion in mesothelioma participants. Rebastinib 50 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle.

Treatment:

Drug: Rebastinib

Drug: Carboplatin

Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5

Experimental group

Description:

Dose expansion in mesothelioma participants. Rebastinib 100 mg BID PO in 21-day cycles in combination with carboplatin administered by IV infusion at AUC5 at Day 1 of each 21-day cycle.

Treatment:

Drug: Rebastinib

Drug: Carboplatin