A Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Paclitaxel in Patients With Advanced or Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT03601897
• Recruitment Status: Recruiting
• First Posted: July 26, 2018
• Last Update Posted: October 23, 2020
• Sponsor: Deciphera Pharmaceuticals LLC
• Information provided by (Responsible Party): Deciphera Pharmaceuticals LLC

Tracking Information

• First Submitted Date: July 5, 2018
• First Posted Date: July 26, 2018
• Last Update Posted Date: October 23, 2020
• Actual Study Start Date: September 19, 2018
• Estimated Primary Completion Date: November 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 27, 2020)

• Adverse Events (Part 1 and Part 2) [ Time Frame: Approximately 36 months ]
• Objective response rate (ORR) (Part 2) [ Time Frame: Approximately 36 months ]

Original Primary Outcome Measures (submitted: July 25, 2018)

Incidence of Adverse Events [ Time Frame: Approximately 24 months ]

Identify the observed adverse events, serious adverse events and discontinuation of study drug due to toxicity to inform determination of recommended phase 2 dose

Current Secondary Outcome Measures (submitted: March 27, 2020)

• Maximum observed concentration (Cmax) of rebastinib [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 (each cycle is 28 days) ]
  Measure the Cmax
• Area under the concentration-time curve (AUC) of rebastinib [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 (each cycle is 28 days) ]
  Measure the AUC
• Progression-free-survival (PFS) [ Time Frame: Approximately 36 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 36 months ]
  Measure of the time from Cycle 1 Day 1 to the first documentation of progressive disease
• Duration of response (DOR) [ Time Frame: Approximately 36 months ]
  Measure of time from PR, CR to disease progression or death due to any cause
• Overall survival (OS) [ Time Frame: Approximately 36 months ]
  Measure of overall survival

Original Secondary Outcome Measures (submitted: July 25, 2018)

• Time to maximum observed concentration at steady state (Tmax,ss) of rebastinib [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]
  Measure the time to maximum observed concentration at steady state
• Maximum observed concentration (Cmax) of rebastinib [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]
  Measure the Cmax
• Maximum observed concentration at steady state of rebastinib [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]
  Measure the maximum observed concentration at steady state
• Concentration observed at the end of the dosing interval (Cmin) of rebastinib in combination with paclitaxel [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]
  Measure the concentration observed at the end of the dosing interval
• Concentration observed at the end of the dosing interval at steady state (Cmin, ss) of rebastinib in combination with paclitaxel [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]
  Measure the concentration observed at the end of the dosing interval at steady state
• Area under the concentration-time curve (AUC) of rebastinib in combination with paclitaxel [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]
  Measure the AUC
• Half-life (T1/2) of rebastinib in combination with paclitaxel [ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]
  Measure the half-life
• Objective response rate (ORR) [ Time Frame: at 8 weeks of the combination therapy, and in the event of disease progression ]
  Objective response rate as determined by confirmed CR + confirmed PR
• Disease control rate (DCR) [ Time Frame: at 8 weeks of the combination therapy, and in the event of disease progression ]
  DCR as determined by complete response [CR] + partial response [PR] + stable disease
• Time to best response [ Time Frame: Approximately 24 months ]
  Measure of time from Cycle 1 Day 1 to PR or CR
• 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 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
• 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.
• 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: Paclitaxel
  Paclitaxel administered by IV infusion at 80 mg/m2

Study Arms

• Experimental: Part 1
  Dose comparison between 50 or 100 mg BID of rebastinib orally (PO) in combination with paclitaxel administered by IV infusion at 80 mg/m2 in repeated 28-day cycles.
  Interventions:

  • Drug: rebastinib
  • Drug: Paclitaxel
• Experimental: Part 2

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

  • Triple-negative and Stage IV inflammatory breast cancer
  • Ovarian cancer
  • Endometrial cancer
  • Gynecological Carcinosarcoma
  Interventions:

  • Drug: rebastinib
  • Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 27, 2020): 201
• Original Estimated Enrollment (submitted: July 25, 2018): 30
• Estimated Study Completion Date: November 1, 2021
• Estimated Primary Completion Date: November 1, 2021 (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 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. 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 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. Venous thrombotic event.
13. Active infection ≥Grade 3.
14. 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: NCT03601897
• Other Study ID Numbers: DCC-2036-01-003
• 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: October 2020