Ripretinib vs Sunitinib for Gastrointestinal Stromal Tumor
(INSIGHT Trial)
Recruiting in Palo Alto (17 mi)
+62 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Deciphera Pharmaceuticals LLC
Must not be taking: CYP3A inhibitors, CYP3A inducers
Disqualifiers: CNS metastases, Heart disease, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a Phase 3, 2-arm, randomized, open-label, global, multicenter study comparing the efficacy of ripretinib to sunitinib in participants with GIST who progressed on first-line treatment with imatinib, harbor co-occurring KIT exons 11+17/18 mutations, and are without KIT exon 9, 13, or 14 mutations. Upon disease progression as determined by an independent radiologic review, participants randomized to sunitinib will be given the option to either crossover to receive ripretinib 150 mg QD or discontinue sunitinib.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but you cannot use strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A or consume grapefruit within 14 days before starting the study drug.
What data supports the effectiveness of the drug ripretinib for gastrointestinal stromal tumors?
Ripretinib is effective as a fourth-line treatment for gastrointestinal stromal tumors, showing increased progression-free survival compared to placebo in the INVICTUS trial. Although it is not superior to sunitinib in second-line treatment, it has a better safety profile with fewer severe side effects.
12345Is Ripretinib generally safe for humans?
Ripretinib has a better safety profile compared to Sunitinib, with fewer severe side effects like high blood pressure. It is generally well-tolerated, with common side effects including increased lipase levels, fatigue, and low phosphate levels in the blood.
12346What makes ripretinib unique compared to sunitinib for treating gastrointestinal stromal tumors?
Ripretinib is unique because it is designed to target a broad range of mutations that can develop resistance to other treatments, and it has a better safety profile with fewer severe side effects compared to sunitinib.
12345Eligibility Criteria
This trial is for adults over 18 with advanced Gastrointestinal Stromal Tumor (GIST) who have progressed after imatinib treatment and have specific KIT exon mutations. Participants must be in good enough health to perform daily activities, not pregnant, agree to use contraception, and cannot have had major surgery recently or certain heart conditions.Inclusion Criteria
My GIST cancer has worsened despite being on imatinib.
Participants must have at least 1 measurable lesion according to mRECIST v1.1 within 21 days prior to the first dose of study drug
I can take care of myself but might not be able to do heavy physical work.
+6 more
Exclusion Criteria
My cancer has a KIT mutation in exon 9, 13, or 14.
I have cancer that has spread to my brain.
I can take pills and do not have issues with absorbing food or need IV feeding.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either ripretinib or sunitinib in 42-day cycles. Ripretinib is dosed continuously, while sunitinib is given for 4 weeks followed by a 2-week break.
Up to approximately 48 months
Crossover
Participants on sunitinib may crossover to receive ripretinib upon disease progression.
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to approximately 48 months
Participant Groups
The study compares the effectiveness of two drugs: Ripretinib and Sunitinib in patients whose GIST has worsened despite initial therapy. It's a global test where people are randomly chosen to receive either drug. If Sunitinib fails, those patients can switch to Ripretinib.
2Treatment groups
Experimental Treatment
Active Control
Group I: RipretinibExperimental Treatment1 Intervention
150 mg QD of ripretinib (3×50 mg tablets) will be dosed continuously in repeated 42-day cycles.
Group II: SunitinibActive Control1 Intervention
50 mg QD of sunitinib (4×12.5 mg capsules) will be dosed in 42-day cycles. Sunitinib will be given continuously for 4 weeks with a 2-week break.
Ripretinib is already approved in United States for the following indications:
🇺🇸 Approved in United States as Qinlock for:
- Gastrointestinal stromal tumors (GIST) in adults who have previously received other medications, including imatinib
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fred Hutchinson Cancer CenterSeattle, WA
The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer CenterColumbus, OH
Boston Medical CenterBoston, MA
Juravinski Cancer CentreHamilton, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Deciphera Pharmaceuticals LLCLead Sponsor
Deciphera Pharmaceuticals, LLCLead Sponsor
References
Testing Ripretinib against Sunitinib in GIST. [2022]According to results from the phase III INTRIGUE trial, ripretinib is not superior to sunitinib as a second-line tyrosine kinase inhibitor for patients with gastrointestinal stromal tumors in terms of progression-free survival. However, ripretinib had a better safety profile and induced fewer grade 3-4 toxicities, including hypertension.
Ripretinib: A Review in Gastrointestinal Stromal Tumours as Fourth-or Later-Line of Therapy. [2022]Ripretinib (Qinlock®) is a small molecule inhibitor of the receptor tyrosine kinases KIT and platelet-derived growth factor receptor α (PDGFRA) and is approved for the treatment of gastrointestinal stromal tumours as a fourth-line of therapy. After successive cycles of treatment, gastrointestinal stromal tumours can carry a wide array of mutations, which makes resistance to treatment more likely. Ripretinib has a dual mechanism of action that allows it to target a broad spectrum of mutations in KIT or PDGFRA. The pivotal phase III INVICTUS trial demonstrated an increase of progression-free survival in patients receiving ripretinib compared with placebo, with efficacy being maintained across patients with KIT exon 9, 11, 13 and 17 mutations. Ripretinib has acceptable tolerability, with the most common drug-related grade 3 or 4 adverse events being lipase increases, hypertension, fatigue and hypophosphataemia. Ripretinib is therefore a valuable additional line of therapy available for the management of gastrointestinal stromal tumours.
Patient-reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after treatment with imatinib in INTRIGUE, a phase 3, open-label study. [2023]In the INTRIGUE trial, ripretinib showed no significant difference versus sunitinib in progression-free survival for patients with advanced gastrointestinal stromal tumour (GIST) previously treated with imatinib. We compared the impact of these treatments on health-related quality of life (HRQoL).
Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. [2023]Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is approved for advanced gastrointestinal stromal tumor (GIST) after imatinib failure. Ripretinib is a switch-control TKI approved for advanced GIST after prior treatment with three or more TKIs, including imatinib. We compared efficacy and safety of ripretinib versus sunitinib in patients with advanced GIST who were previously treated with imatinib (INTRIGUE, ClinicalTrials.gov identifier: NCT03673501).
Intrigue: Phase III study of ripretinib versus sunitinib in advanced gastrointestinal stromal tumor after imatinib. [2020]Ripretinib (DCC-2618) is a novel, type II tyrosine switch control inhibitor designed to broadly inhibit activating and drug-resistant mutations in KIT and PDGFRA. Ripretinib has emerged as a promising investigational agent for the treatment of gastrointestinal stromal tumor owing to targeted inhibition of secondary resistance mutations that may develop following treatment with prior line(s) of tyrosine kinase inhibitors. Here we describe the rationale and design of intrigue (NCT03673501), a global, randomized (1:1), open-label, Phase III study comparing the safety and efficacy of ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor following imatinib. The primary end point is progression-free survival and key secondary objectives include objective response rate and overall survival. Clinical Trial Registration: NCT03673501.
Efficacy and Safety of Ripretinib in Chinese Patients with Advanced Gastrointestinal Stromal Tumors as a Fourth- or Later-Line Therapy: A Multicenter, Single-Arm, Open-Label Phase II Study. [2023]This is a phase II multicenter, single-arm, open-label study assessing the efficacy, safety, and pharmacokinetics (PK) of ripretinib in Chinese patients with advanced gastrointestinal stromal tumor (GIST) as a fourth- or later-line therapy. It was designed to show consistency with the phase III INVICTUS study.