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

• ClinicalTrials.gov Identifier: NCT03717415
• Recruitment Status: Recruiting
• First Posted: October 24, 2018
• Last Update Posted: August 28, 2020
• Sponsor: Deciphera Pharmaceuticals LLC
• Information provided by (Responsible Party): Deciphera Pharmaceuticals LLC

Tracking Information

• First Submitted Date: October 19, 2018
• First Posted Date: October 24, 2018
• Last Update Posted Date: August 28, 2020
• Actual Study Start Date: January 2, 2019
• Estimated Primary Completion Date: March 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 22, 2018)

• Adverse Events (Part 1 and Part 2) [ Time Frame: Approximately 24 months ]
• Objective response rate (ORR) (Part 2) [ Time Frame: Approximately 24 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 21, 2019)

• Maximum observed concentration (Cmax) of rebastinib [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (each cycle is 21 days) ]
  Measure the Cmax
• Area under the concentration-time curve (AUC) of rebastinib [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (each cycle is 21 days) ]
  Measure the AUC
• Progression-free-survival (PFS) [ Time Frame: Approximately 24 months ]
  Measure of the time from Cycle 1 Day 1 to disease progression or death due to any cause
• Time to progression (TTP) [ Time Frame: Approximately 24 months ]
  Measure of the time from Cycle 1 Day 1 to the first documentation of progressive disease
• Duration of response (DOR) [ Time Frame: Approximately 24 months ]
  Measure of time from first PR, CR to disease progression or death due to any cause
• Overall survival (OS) [ Time Frame: Approximately 24 months ]
  Measure of the interval between Cycle 1 Day 1 until date of death from any cause

Original Secondary Outcome Measures (submitted: October 22, 2018)

• Maximum observed concentration (Cmax) of rebastinib [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (each cycle is 21 days) ]
  Measure the Cmax
• Area under the concentration-time curve (AUC) of rebastinib [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1 (each cycle is 21 days) ]
  Measure the AUC
• Progression-free-survival (PFS) [ Time Frame: Approximately 24 months ]
  Measure of the time from Cycle 1 Day 1 to disease progression or death due to any cause
• Time to progression (TTP) [ Time Frame: Approximately 24 months ]
  Measure of the time from Cycle 1 Day 1 to the first documentation of progressive disease
• Duration of response (DOR) [ Time Frame: Approximately 24 months ]
  Measure of time from PR, CR to disease progression or death due to any cause
• Overall survival (OS) [ Time Frame: Approximately 24 months ]
  Measure of overall survival

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Rebastinib (DCC-2036) in Combination With Carboplatin in Patients With Advanced or Metastatic Solid Tumors
• Official Title: 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
• 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 patients with advanced or metastatic solid tumors.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Locally Advanced or Metastatic Solid Tumor

Intervention

• Drug: rebastinib
  25 mg tablets or 75 mg tablets
  Other Name: DCC-2036
• Drug: Carboplatin
  Carboplatin administered by IV infusion at AUC5 or AUC6

Study Arms

• Experimental: Part 1
  Dose comparison between 50 or 100 mg BID of rebastinib orally (PO) dosed in 21-day cycles in combination with carboplatin administered by IV infusion at either AUC5 or AUC6 once every 3 weeks
  Interventions:

  • Drug: rebastinib
  • Drug: Carboplatin
• Experimental: Part 2

  Dose expansion in the following tumor types at the recommended Phase 2 dose (RP2D) of rebastinib in combination with carboplatin

  • Triple-negative breast cancer
  • Ovarian cancer
  • Mesothelioma
  Interventions:

  • Drug: rebastinib
  • Drug: Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 22, 2018): 117
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 1, 2022
• Estimated Primary Completion Date: March 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials; 785-830-2100; clinicaltrials@deciphera.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03717415
• Other Study ID Numbers: DCC-2036-01-004
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Deciphera Pharmaceuticals LLC
• Study Sponsor: Deciphera Pharmaceuticals LLC
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Deciphera Pharmaceuticals LLC
• Verification Date: August 2020