A Study of Rebastinib (DCC-2036) in Combination With Carboplatin in Patients With Advanced or Metastatic Solid Tumors

NCT03717415 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: DCC-2036-01-004
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Locally Advanced or Metastatic Solid Tumor

Keywords

rebastinib; breast cancer; ovarian cancer; mesothelioma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  Number of participants who experienced serious adverse events (SAE) and adverse events (AE).

  Baseline up to 2.32 years

• Objective Response Rate (ORR) (Dose Expansion Phase)

  Percentage of participants who achieved an objective response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.

  Time from CR or PR to disease progression or death due to any cause (Up to 1.53 years)

Secondary Outcomes (7)

• Objective Response Rate (ORR) (Dose Escalation Phase)

  Time from CR or PR to disease progression or death due to any cause (Up to 1.53 years)

• Duration of Response (DOR)

  Time from PR or CR to PD or Death due to Any Cause (up to 1.53 years)

• Time to Progression (TTP)

  First Dose of Study Drug to PD (Up to 1.63 years)

• Progression-free-survival (PFS)

  First Dose of Study Drug to PD or Death due to Any Cause (up to 1.63 years)

• Overall Survival (OS)

  Baseline to death due to any cause (Up to 2.12 years)

Study Arms (9)

Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5

EXPERIMENTAL

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.

Drug: Rebastinib; Drug: Carboplatin

Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5

EXPERIMENTAL

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.

Drug: Rebastinib; Drug: Carboplatin

Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6

EXPERIMENTAL

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.

Drug: Rebastinib; Drug: Carboplatin

Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5

EXPERIMENTAL

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.

Drug: Rebastinib; Drug: Carboplatin

Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5

EXPERIMENTAL

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.

Drug: Rebastinib; Drug: Carboplatin

Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5

EXPERIMENTAL

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.

Drug: Rebastinib; Drug: Carboplatin

Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5

EXPERIMENTAL

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.

Drug: Rebastinib; Drug: Carboplatin

Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5

EXPERIMENTAL

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.

Drug: Rebastinib; Drug: Carboplatin

Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5

EXPERIMENTAL

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.

Drug: Rebastinib; Drug: Carboplatin

Interventions

Rebastinib DRUG

Administered orally

Also known as: DCC-2036

Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5; Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5; Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6; Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5; Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5; Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5; Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5; Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5; Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5

Carboplatin DRUG

Administered by IV infusion

Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5; Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5; Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6; Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5; Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5; Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5; Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5; Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5; Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥18 years of age at the time of informed consent.
• Part 1 (Dose Escalation). Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which carboplatin is considered appropriate treatment.
• Part 2 (Dose Expansion)
• Previously treated, triple-negative breast cancer.
• Recurrent platinum-sensitive ovarian cancer.
• Histologically confirmed pleural or peritoneal malignant mesothelioma.
• ECOG performance status of ≤2.
• Able to provide an archival tumor tissue sample.
• Adequate organ function and bone marrow reserve.
• If a female of childbearing potential, must have a negative pregnancy test prior to enrollment.
• Patient must provide signed consent to participate in the study and is willing to comply with study-specific procedures.

You may not qualify if:

• Received prior anticancer or other investigational therapy within 28 days or 5× the half-life (whichever is shorter) prior to the first dose.
• Not recovered from prior-treatment toxicities to Grade ≤1 or baseline.
• Peripheral neuropathy of any etiology \>Grade 1.
• Concurrent malignancy.
• Known active CNS metastases.
• Use of systemic corticosteroids.
• Known retinal neovascularization, macular edema or macular degeneration.
• History or presence of clinically relevant cardiovascular abnormalities.
• QTcF \>450 ms in males or \>470 ms in females.
• Left ventricular ejection fraction (LVEF) \<50% at screening.
• Arterial thrombotic or embolic events.
• Symptomatic venous thrombotic event.
• Active infection ≥Grade 3.
• Known HIV or HCV infection only if taking medications excluded per protocol, active HBV, or active HCV infection.
• Use of proton pump inhibitors.

Sponsors & Collaborators

• Deciphera Pharmaceuticals, LLC: lead

Study Sites (9)

University of California San Francisco (UCSF)

San Francisco, California, 94115, United States

Location

UCLA Medical Center

Santa Monica, California, 90404, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78240, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Breast Neoplasms; Ovarian Neoplasms; Mesothelioma

Interventions

rebastinib; DCC-2036; Carboplatin

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Limitations and Caveats

Trial terminated on May 23, 2022, due to development program termination.

Results Point of Contact

• Title: Clinical Trials
• Organization: Deciphera Pharmaceuticals, LLC

clinicaltrials@deciphera.com

785-830-2100

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2018
• First Posted: October 24, 2018
• Study Start: January 2, 2019
• Primary Completion: May 1, 2022
• Study Completion: November 1, 2022
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)