Clinical trial NCT03717415: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Locally Advanced or Metastatic Solid Tumor
Keywords: rebastinib
breast cancer
ovarian cancer
mesothelioma
Lead sponsor: Deciphera Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2018-10-24
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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 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.

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Baseline up to 2.32 years
measure: Objective Response Rate (ORR) (Dose Expansion Phase)
timeFrame: Time from CR or PR to disease progression or death due to any cause (Up to 1.53 years)
Secondary outcomes:
measure: Objective Response Rate (ORR) (Dose Escalation Phase)
timeFrame: Time from CR or PR to disease progression or death due to any cause (Up to 1.53 years)
measure: Duration of Response (DOR)
timeFrame: Time from PR or CR to PD or Death due to Any Cause (up to 1.53 years)
measure: Time to Progression (TTP)
timeFrame: First Dose of Study Drug to PD (Up to 1.63 years)
measure: Progression-free-survival (PFS)
timeFrame: First Dose of Study Drug to PD or Death due to Any Cause (up to 1.63 years)
measure: Overall Survival (OS)
timeFrame: Baseline to death due to any cause (Up to 2.12 years)
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1)
timeFrame: Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 Days)
measure: PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1)
timeFrame: Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 Days)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF)
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
References: