Clinical trial NCT05080621: Ripretinib in Combination With Binimetinib in Patients With Gastrointestinal Stromal Tumor (GIST)
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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Gastrointestinal Stromal Tumors
Lead sponsor: Deciphera Pharmaceuticals, LLC
Sponsor class: INDUSTRY
First posted: 2021-10-18
Enrollment: 0
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: 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).


Eligibility 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

Primary outcomes:
measure: Safety/tolerability of oral ripretinib in combination with binimetinib: incidence of adverse events
timeFrame: Approximately 12 months
measure: Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose
timeFrame: Approximately 12 months
measure: Expansion Phase Only: Evaluate the objective response rate (ORR) of ripretinib in combination with binimetinib by modified RECIST
timeFrame: Approximately 36 months
Secondary outcomes:
measure: Determine the time to maximum observed concentration (tmax) profile of oral ripretinib in combination with binimetinib
timeFrame: 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: Determine the maximum observed concentration (Cmax) profile of oral ripretinib in combination with binimetinib
timeFrame: 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: Determine the minimum observed concentration (Cmin) profile of oral ripretinib in combination with binimetinib
timeFrame: 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: Determine the area under the concentration-time curve (AUC) profile of oral ripretinib in combination with binimetinib
timeFrame: 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: 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)
timeFrame: Approximately 36 months
measure: Evaluate the progression-free survival (PFS) of ripretinib in combination with binimetinib
timeFrame: Approximately 36 months
measure: Evaluate the overall survival (OS) of ripretinib in combination with binimetinib
timeFrame: Approximately 36 months
measure: Evaluate the duration of response (DOR) of ripretinib in combination with binimetinib
timeFrame: Approximately 36 months
measure: Evaluate the clinical benefit rate (CBR) of ripretinib in combination with binimetinib
timeFrame: Approximately 36 months
measure: Evaluate the time to response (TTR) of ripretinib in combination with binimetinib
timeFrame: Approximately 36 months
Other outcomes:
Locations:
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