We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ripretinib in Combination With Binimetinib in Patients With Gastrointestinal Stromal Tumor (GIST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05080621
Recruitment Status : Withdrawn (The Sponsor decided to discontinue this study due to a corporate restructuring intended to prioritize clinical development of select programs. No patients enrolled in this study and no patients received investigational product.)
First Posted : October 18, 2021
Last Update Posted : January 5, 2022
Sponsor:
Information provided by (Responsible Party):
Deciphera Pharmaceuticals LLC

Brief Summary:
Multicenter, open-label Phase 1b/2 study of ripretinib in combination with binimetinib in patients with gastrointestinal stromal tumor (GIST). There will be 2 distinct parts in this study: Dose Escalation (Phase 1) and Expansion (Phase 2).

Condition or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumors Drug: Ripretinib Drug: binimetinib Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Ripretinib in Combination With Binimetinib in Patients With Gastrointestinal Stromal Tumor (GIST)
Estimated Study Start Date : November 2021
Estimated Primary Completion Date : November 2025
Estimated Study Completion Date : May 2027


Arm Intervention/treatment
Experimental: Escalation

Escalation Phase: Increasing doses of ripretinib in combination with increase doses of binimetinib in patients with advanced GIST who have progressed on at least imatinib or are intolerant to imatinib and are ripretinib naïve in repeated 28-day cycles.

Participants may remain on treatment until disease progression, unacceptable toxicity, or withdrawal of consent

Drug: Ripretinib
50 mg tablets
Other Name: DCC-2618, QINLOCK

Drug: binimetinib
15 mg tablets
Other Name: Mektovi

Experimental: Expansion

Ripretinib in combination with binimetinib at the recommended Phase 2 dose (RP2D) in patients with advanced GIST who have progressed on imatinib or are intolerant to imatinib and are naïve.

Participants may remain on treatment until disease progression, unacceptable toxicity, or withdrawal of consent

Drug: Ripretinib
50 mg tablets
Other Name: DCC-2618, QINLOCK

Drug: binimetinib
15 mg tablets
Other Name: Mektovi




Primary Outcome Measures :
  1. Safety/tolerability of oral ripretinib in combination with binimetinib: incidence of adverse events [ Time Frame: Approximately 12 months ]
    Adverse events [TEAEs, SAEs, AESIs], dose reduction, dose interruption, or discontinuation, vital signs (heart rate [beats/min], and changes in laboratory parameters (chemistry, hematology, urinalysis, coagulation).

  2. Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose [ Time Frame: Approximately 12 months ]
  3. Expansion Phase Only: Evaluate the objective response rate (ORR) of ripretinib in combination with binimetinib by modified RECIST [ Time Frame: Approximately 36 months ]
    Measure ORR


Secondary Outcome Measures :
  1. Determine the time to maximum observed concentration (tmax) profile of oral ripretinib in combination with binimetinib [ Time Frame: Cycle 1 Day 1, and Cycle 1 Day15 (pre-dose and at multiple time points [up to 8 hours] post-dose). Each cycle is 28 days ]
    Measure Tmax

  2. Determine the maximum observed concentration (Cmax) profile of oral ripretinib in combination with binimetinib [ Time Frame: Cycle 1 Day 1, and Cycle 1 Day15 (pre-dose and at multiple time points [up to 8 hours] post-dose). Each cycle is 28 days ]
    Measure Cmax

  3. Determine the minimum observed concentration (Cmin) profile of oral ripretinib in combination with binimetinib [ Time Frame: Cycle 1 Day 1, and Cycle 1 Day15 (pre-dose and at multiple time points [up to 8 hours] post-dose). Each cycle is 28 days ]
    Measure Cmin

  4. Determine the area under the concentration-time curve (AUC) profile of oral ripretinib in combination with binimetinib [ Time Frame: Cycle 1 Day 1, and Cycle 1 Day15 (pre-dose and at multiple time points [up to 8 hours] post-dose). Each cycle is 28 days ]
    Measure AUC

  5. Evaluate the objective response rate (ORR) of ripretinib in combination with binimetinib by modified RECIST (escalation phase only) and Choi criteria (escalation and expansion phases) [ Time Frame: Approximately 36 months ]
    Measure ORR

  6. Evaluate the progression-free survival (PFS) of ripretinib in combination with binimetinib [ Time Frame: Approximately 36 months ]
    Measure PFS

  7. Evaluate the overall survival (OS) of ripretinib in combination with binimetinib [ Time Frame: Approximately 36 months ]
    Measure OS

  8. Evaluate the duration of response (DOR) of ripretinib in combination with binimetinib [ Time Frame: Approximately 36 months ]
    Measure DOR

  9. Evaluate the clinical benefit rate (CBR) of ripretinib in combination with binimetinib [ Time Frame: Approximately 36 months ]
    Measure CBR

  10. Evaluate the time to response (TTR) of ripretinib in combination with binimetinib [ Time Frame: Approximately 36 months ]
    Measure TTR



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients ≥18 years of age with advanced GIST (unresectable or metastatic).
  2. Must have at least progressed on imatinib or have documented intolerance to imatinib.
  3. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  4. Patients must have a histologic diagnosis of GIST.
  5. If a female of childbearing potential, must have a negative pregnancy test.
  6. Adequate organ function and bone marrow function

Exclusion Criteria:

  1. Received prior anticancer therapy within 14 days or 5× the half-life whichever is longer) prior to the first dose.
  2. Ongoing or prior participation in the DCC-2618-03-002 study.
  3. Prior therapy with ripretinib.
  4. Prior therapy with MEK inhibitor.
  5. History of certain ocular disorders.
  6. History of clinically significant hepatobiliary disease.
  7. Known active central nervous system metastases.
  8. History or presence of clinically relevant cardiovascular abnormalities.
  9. Systemic arterial or venous thrombotic or embolic events within 6 months of first dose.
  10. History of acute or chronic pancreatitis
  11. History of chronic inflammatory bowel disease or Crohn's disease requiring intervention within 12 months of first dose.
  12. Gastrointestinal abnormalities including but not limited to:

    • inability to take oral medication,
    • malabsorption syndromes
Layout table for additonal information
Responsible Party: Deciphera Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT05080621    
Other Study ID Numbers: DCC-2618-01-008
First Posted: October 18, 2021    Key Record Dates
Last Update Posted: January 5, 2022
Last Verified: December 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases