Ripretinib vs Sunitinib for Gastrointestinal Stromal Tumors

(INTRIGUE Trial)

Not currently recruiting at 136 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Deciphera Pharmaceuticals, LLC

Must not be taking: BCRP inhibitors

Disqualifiers: CNS metastases, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness of two treatments, ripretinib (DCC-2618) and sunitinib, for individuals with gastrointestinal stromal tumors (GIST) who did not respond well to or could not tolerate their first cancer treatment, imatinib. The researchers seek to determine which treatment better manages GIST. Participants must have a confirmed diagnosis of GIST and have experienced issues with imatinib. This trial offers an opportunity to contribute to research that might improve future treatment options for GIST. As a Phase 3 trial, it represents the final step before FDA approval, providing participants a chance to help validate a potentially effective treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain drugs that affect specific proteins (BCRP transporters) within 14 days before starting the study drug. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ripretinib is usually well-tolerated by patients with advanced gastrointestinal stromal tumors (GIST). In earlier studies involving 45 patients, most side effects were mild or moderate, such as hair loss and tiredness, while serious side effects were less common.

Studies have also found sunitinib to be generally well-tolerated. Common side effects include tiredness and diarrhea, though serious side effects like high blood pressure and heart issues can occur.

Both treatments have been tested in many patients, providing a good understanding of their safety. However, as with any treatment, individual reactions may vary, so discussing possible side effects with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for GIST?

Most treatments for gastrointestinal stromal tumors (GIST) work by inhibiting specific enzymes that drive cancer growth. Ripretinib, however, introduces a novel mechanism by targeting a broader range of these enzymes, potentially overcoming resistance that develops with other therapies like Sunitinib. Researchers are excited about Ripretinib because it offers continuous dosing without breaks, which might enhance its effectiveness and reduce the chance of tumor progression. This could provide patients with a more consistent treatment experience and potentially improve outcomes compared to the current standard of care.

What evidence suggests that this trial's treatments could be effective for gastrointestinal stromal tumors?

This trial will compare ripretinib and sunitinib for treating advanced gastrointestinal stromal tumors (GIST). Research has shown that ripretinib is promising for treating GIST. In the INVICTUS trial, patients taking ripretinib lived without their cancer worsening for an average of 6.3 months, compared to just 1 month for those taking a placebo. Additionally, 17% of patients experienced tumor shrinkage or disappearance, and 66% had stable disease without growth.

For sunitinib, studies have shown it works well for GIST patients who no longer respond to imatinib, the first-line treatment. Sunitinib has been used for years and is known to help patients live longer without their cancer worsening. Both treatments offer hope for those with advanced GIST, but ripretinib might provide a new option with potentially better results. Participants in this trial will receive either ripretinib or sunitinib, allowing for a direct comparison of their effectiveness. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Gastrointestinal Stromal Tumors (GIST) who've had issues with the first-line treatment, imatinib. They need a confirmed diagnosis and must provide tissue samples for testing. Participants should be relatively fit (ECOG PS ≤2), not pregnant, willing to use contraception, have at least one measurable tumor lesion, and stable organ function.

Inclusion Criteria

If you can have children, you must agree to use birth control as detailed in the study rules.

I have a tumor that can be measured by scans.

I have a GIST diagnosis and can provide a past or new tumor sample.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ripretinib or sunitinib in 6-week cycles

6 weeks per cycle

Continuous dosing for ripretinib; 4 weeks on, 2 weeks off for sunitinib

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2.1 years

What Are the Treatments Tested in This Trial?

Interventions

• DCC-2618
• Sunitinib

Trial Overview The study compares two drugs: Ripretinib taken daily in continuous 6-week cycles versus Sunitinib taken daily for 4 weeks on/2 weeks off in similar cycles. It's designed to see which drug works better after imatinib fails in advanced GIST patients.

How Is the Trial Designed?

Group I: Ripretinib Experimental Treatment 1 Intervention

Ripretinib (150 mg) once a day continuous dosing for 6-week (42 days) cycles

Group II: Sunitinib Active Control 1 Intervention

Sunitinib (50 mg) once a day in 6-week (42 days) cycles with 4 weeks continuous dosing followed by 2 week break.

Who Is Running the Clinical Trial?

Deciphera Pharmaceuticals, LLC

Lead Sponsor

Trials

19

Recruited

2,100+

Deciphera Pharmaceuticals LLC

Lead Sponsor

Trials

17

Recruited

1,900+

Published Research Related to This Trial

In the INTRIGUE trial, patients with advanced gastrointestinal stromal tumors (GIST) treated with ripretinib reported better health-related quality of life (HRQoL) compared to those treated with sunitinib, particularly at the 29-day assessments.

Patients receiving ripretinib also experienced a longer time without symptoms or severe treatment-related side effects, averaging 173 days compared to 126 days for those on sunitinib, suggesting ripretinib may offer a clinically meaningful benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after treatment with imatinib in INTRIGUE, a phase 3, open-label study. Gelderblom, H., Jones, RL., Blay, JY., et al.[2023]

Ripretinib is a new type II tyrosine switch control inhibitor that targets both activating and drug-resistant mutations in KIT and PDGFRA, making it a promising treatment for gastrointestinal stromal tumors, especially after previous treatments with other tyrosine kinase inhibitors.

The ongoing Phase III study (NCT03673501) is comparing the safety and efficacy of ripretinib to sunitinib in patients with advanced gastrointestinal stromal tumors, focusing on progression-free survival as the primary endpoint.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrigue: Phase III study of ripretinib versus sunitinib in advanced gastrointestinal stromal tumor after imatinib. Nemunaitis, J., Bauer, S., Blay, JY., et al.[2020]

Sunitinib malate (Sutent) was approved by the FDA for treating gastrointestinal stromal tumors (GIST) after patients showed disease progression or intolerance to imatinib, demonstrating a median time-to-tumor progression of 27.3 weeks compared to 6.4 weeks for placebo.

In advanced renal cell carcinoma, sunitinib showed partial response rates of 25.5% and 36.5% in two studies, with median response durations of 27.1 and 54 weeks, although it was associated with common side effects like diarrhea and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Goodman, VL., Rock, EP., Dagher, R., et al.[2022]

Ripretinib demonstrated a higher objective response rate compared to sunitinib in patients with advanced gastrointestinal stromal tumors (GIST) who had previously been treated with imatinib, showing 23.9% versus 14.6% respectively.

Although ripretinib was not superior to sunitinib in terms of progression-free survival (PFS), it had a significantly better safety profile with fewer severe adverse events (41.3% for ripretinib vs. 65.6% for sunitinib), indicating it may be a more tolerable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. Bauer, S., Jones, RL., Blay, JY., et al.[2023]

In the phase III INTRIGUE trial, ripretinib was found to be not superior to sunitinib for progression-free survival in patients with gastrointestinal stromal tumors.

Ripretinib demonstrated a better safety profile, resulting in fewer severe side effects (grade 3-4 toxicities), including lower rates of hypertension compared to sunitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testing Ripretinib against Sunitinib in GIST. [2022]

In a study of 55 Chinese patients with imatinib-resistant or -intolerant gastrointestinal stromal tumors (GISTs), sunitinib demonstrated effectiveness with a median overall survival of 86 weeks and a median progression-free survival of 35 weeks for those on a continuous daily dose of 37.5 mg.

Patients with KIT exon 9 mutations experienced significantly longer progression-free survival compared to those with KIT exon 11 mutations or wild-type GISTs, indicating that genetic factors can influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sunitinib in Chinese patients with imatinib-resistant or -intolerant gastrointestinal stromal tumors. Li, J., Gao, J., Hong, J., et al.[2022]

Sunitinib malate has shown long-term efficacy and safety in treating metastatic renal cell carcinoma (mRCC) and advanced imatinib-refractory gastrointestinal stromal tumors (GIST), as demonstrated in four patient cases.

Effective management of adverse events (AEs) allowed patients to continue long-term therapy with sunitinib, leading to sustained clinical benefits and prolonged responses in both mRCC and GIST cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyrosine kinase inhibition in renal cell carcinoma and gastrointestinal stromal tumours: case reports. Schöffski, P., Bukowski, R., Flodgren, P., et al.[2020]

Sunitinib malate significantly improves time to progression and progression-free survival in adult patients with gastrointestinal stromal tumors (GIST) who are resistant or intolerant to imatinib, with a hazard ratio for overall survival of 0.49, indicating a substantial benefit over placebo.

While sunitinib malate is effective, it is associated with a higher incidence of hematologic adverse effects such as leucopenia and neutropenia, as well as other side effects like fatigue and hand-foot syndrome, suggesting that while it is a recommended second-line therapy, monitoring for these adverse effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib malate for gastrointestinal stromal tumour in imatinib mesylate-resistant patients: recommendations and evidence. Younus, J., Verma, S., Franek, J., et al.[2021]

Citations

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Second-line treatment patterns and outcomes of advanced ... Our preliminary results suggest that ripretinib may offer superior clinical benefits for patients with primary KIT exon 11 mutations after ...

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NCT03353753 | Phase 3 Study of DCC-2618 vs Placebo in ... This is a 2-arm, randomized, placebo-controlled, double-blind, international, multicenter study comparing the efficacy of ripretinib (DCC-2618) to placebo ...

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Effect and safety of ripretinib in the treatment of advanced ... The objective response rate (ORR) of the RPT-treated advanced GIST was 17% (95%CI: 0.11-0.27), while the disease control rate (DCR) was 66% (95%CI: 0.59-0.73).

4. onclive.com onclive.com/view/ripretinib-use-in-advanced-gastrointestinal-stromal-tumors

Ripretinib Use in Advanced Gastrointestinal Stromal Tumors The INVICTUS trial data revealed impressive efficacy with median progression-free survival of 6.3 months vs 1 month for placebo, along with ...

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A Study of DCC-2618 (Ripretinib) In Patients With ... The primary objective of this trial is to evaluate the progress free survival (PFS) of DCC-2618 in patients with advanced gastrointestinal stromal tumors who ...

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Updated Overall Survival and Long-Term Safety With ... Recent preclinical data propose that resistant KIT mutations may be common in GIST cells from heavily pretreated patients (median 4 therapy ...

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NCT02571036 | A Safety, Tolerability and PK Study of DCC ... A multicenter Phase 1, open-label study of DCC-2618 to assess safety, tolerability, efficacy, and pharmacokinetics in patients with advanced malignancies.

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Overall survival and long-term safety with ripretinib vs ... Overall survival and long-term safety with ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor previously treated ...

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Emerging Data on the Safety and Efficacy of Ripretinib for ... Emerging Data on the Safety and Efficacy of Ripretinib for the Treatment of Gastrointestinal Stromal Tumors · Clinical Efficacy · Dosing and Side ...

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Efficacy and Safety of Ripretinib in Advanced ... Ripretinib is a novel drug used to treat patients with advanced gastrointestinal stromal tumors. We investigated its efficacy and safety in a group of 45 ...