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

An Open Label, Multicenter, Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Carboplatin to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced or Metastatic Solid Tumors

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.

Study Overview

• Status: Terminated
• Conditions: Locally Advanced or Metastatic Solid Tumor
• Intervention / Treatment: Drug: Rebastinib; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • University of California San Francisco (UCSF)
    • Santa Monica, California, United States, 90404
      • UCLA Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78240
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Cohort 1 Escalation Rebastinib 50 mg + Carboplatin AUC5; 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; Administered orally; Other Names: DCC-2036; Drug: Carboplatin; Administered by IV infusion
Experimental: Part 1 Cohort 2 Escalation Rebastinib 100 mg + Carboplatin AUC5; 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; Administered orally; Other Names: DCC-2036; Drug: Carboplatin; Administered by IV infusion
Experimental: Part 1 Cohort 3 Escalation Rebastinib 100 mg + Carboplatin AUC6; 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; Administered orally; Other Names: DCC-2036; Drug: Carboplatin; Administered by IV infusion
Experimental: Part 2 Cohort 1 Expansion Rebastinib 50 mg + Carboplatin AUC5; 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; Administered orally; Other Names: DCC-2036; Drug: Carboplatin; Administered by IV infusion
Experimental: Part 2 Cohort 1 Expansion Rebastinib 100 mg + Carboplatin AUC5; 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; Administered orally; Other Names: DCC-2036; Drug: Carboplatin; Administered by IV infusion
Experimental: Part 2 Cohort 2 Expansion Rebastinib 50 mg + Carboplatin AUC5; 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; Administered orally; Other Names: DCC-2036; Drug: Carboplatin; Administered by IV infusion
Experimental: Part 2 Cohort 2 Expansion Rebastinib 100 mg + Carboplatin AUC5; 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; Administered orally; Other Names: DCC-2036; Drug: Carboplatin; Administered by IV infusion
Experimental: Part 2 Cohort 3 Expansion Rebastinib 50 mg + Carboplatin AUC5; 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; Administered orally; Other Names: DCC-2036; Drug: Carboplatin; Administered by IV infusion
Experimental: Part 2 Cohort 3 Expansion Rebastinib 100 mg + Carboplatin AUC5; 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; Administered orally; Other Names: DCC-2036; Drug: Carboplatin; Administered by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) (Dose Escalation 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)
Duration of Response (DOR)	Time from first partial response (PR) or complete response (CR) to disease progression (PD) or death due to any cause. Evaluation of radiographic disease assessment 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 PR or CR to PD or Death due to Any Cause (up to 1.53 years)
Time to Progression (TTP)	Time from first dose of study drug to the first documentation of progressive disease (PD). Participants were considered to have progressive disease if they had documented progression based on radiologic assessment according to RECIST v1.1. RECIST v1.1 defined disease progression as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions.	First Dose of Study Drug to PD (Up to 1.63 years)
Progression-free-survival (PFS)	Time from first dose of study drug to disease progression (PD) or death due to any cause. Participants who undergo surgical resection of target or non-target lesions, who have received other anticancer treatments, including surgical resection or radiation (other than palliative radiation to pre-existing bone metastases'), or who do not have a documented date of progression or death due to any cause will be censored at the date of the last assessment. Disease progression per RECIST v1.1 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.	First Dose of Study Drug to PD or Death due to Any Cause (up to 1.63 years)
Overall Survival (OS)	Time from baseline C1 D1 to date of death due to any cause. Participants who are still alive or who are lost to follow-up will be censored at the date of last contact.	Baseline to death due to any cause (Up to 2.12 years)
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1)	Cmax of rebastinib	Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 Days)
PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1)	Measure the AUC 0-3 hours	Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 Days)

Collaborators and Investigators

• Sponsor: Deciphera Pharmaceuticals, LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2019
• Primary Completion (Actual): May 1, 2022
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: October 19, 2018
• First Submitted That Met QC Criteria: October 22, 2018
• First Posted (Actual): October 24, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; mesothelioma; ovarian cancer; rebastinib
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Rebastinib; Carboplatin
• Other Study ID Numbers: DCC-2036-01-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No