Clinical trial NCT03601897: A Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Paclitaxel 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 Paclitaxel 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
paclitaxel
breast cancer
ovarian cancer
endometrial cancer
gynecological carcinosarcoma
malignant mixed Mullerian tumor (MMMT)
Lead sponsor: Deciphera Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2018-07-26
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_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 paclitaxel designed to evaluate the safety, tolerability, and pharmacokinetics (PK) in patients 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 Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which paclitaxel is considered appropriate treatment
3. Part 2

   * Triple-negative and Stage IV inflammatory breast cancer
   * Recurrent ovarian cancer
   * Recurrent, metastatic or high-risk endometrial cancer
   * Advanced (stage III or IV), or recurrent gynecological carcinosarcoma

     * Homologous or heterologous type carcinosarcoma (malignant mixed Mullerian tumor \[MMMT\] allowed
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 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 prior to the first dose
2. Not recovered from prior-treatment toxicities to Grade ≤1
3. Peripheral neuropathy of any etiology \>Grade 1
4. Concurrent malignancy
5. Known active central nervous system (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. QT interval corrected by Fridericia's formula (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. Venous thrombotic event
13. Active infection ≥Grade 3
14. Human immunodeficiency virus (HIV) or hepatitis C (HCV) infection only if taking medications excluded per protocol, active hepatitis B (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 2.89 years
measure: Objective Response Rate (ORR) (Part 2 Expansion)
timeFrame: Baseline to PD or Death due to Any Cause (Up to 1.54 years)
Secondary outcomes:
measure: Objective Response Rate (ORR) (Part 1 Escalation)
timeFrame: Baseline to PD or Death due to Any Cause (Up to 0.92 years)
measure: Duration of Response (DOR)
timeFrame: Time from CR or PR to PD or Death due to Any Cause (Up to 1.54 years)
measure: Time to Progression (TTP)
timeFrame: First Dose of Study Drug to PD (Up to 2.61 years)
measure: Progression-free-survival (PFS)
timeFrame: First Dose of Study Drug to PD or Death due to Any Cause (Up to 2.61 years)
measure: Overall Survival (OS)
timeFrame: First Dose of Study Drug to Death due to Any Cause (Up to 2.82 years)
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1)
timeFrame: Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days)
measure: PK: Area Under the Concentration-time Curve (AUC) 0-6 Hours of Rebastinib (Part 1)
timeFrame: Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Aurora
country: United States
facility: University of Colorado Denver- Anschutz Medical Center
state: Colorado
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Kansas City
country: United States
facility: The University of Kansas Clinical Research Center
state: Kansas
city: Boston
country: United States
facility: Dana-Farber
state: Massachusetts
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Lake Success
country: United States
facility: Northwell Health/Monter Cancer Center
state: New York
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Women & Infants Hospital
state: Rhode Island
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: Houston
country: United States
facility: Oncology Consultants- Texas Medical Center
state: Texas
Study officials:
References: