Gastrointestinal Stromal TumorsPhase 1/2NCT05080621
Ripretinib in Combination With Binimetinib in Patients With Gastrointestinal Stromal Tumor (GIST)
A Phase 1/2 study testing Ripretinib and binimetinib in people with Gastrointestinal Stromal Tumors, run by Deciphera Pharmaceuticals, LLC.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Stromal Tumors
- What is being tested?
- Ripretinib and binimetinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2021to May 2027
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥18 years of age with advanced GIST (unresectable or metastatic).
- Must have at least progressed on imatinib or have documented intolerance to imatinib.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Patients must have a histologic diagnosis of GIST.
- If a female of childbearing potential, must have a negative pregnancy test.
- Adequate organ function and bone marrow function
Who cannot join
- Received prior anticancer therapy within 14 days or 5× the half-life whichever is longer) prior to the first dose.
- Ongoing or prior participation in the DCC-2618-03-002 study.
- Prior therapy with ripretinib.
- Prior therapy with MEK inhibitor.
- History of certain ocular disorders.
- History of clinically significant hepatobiliary disease.
Show all 14Show fewer
- Known active central nervous system metastases.
- History or presence of clinically relevant cardiovascular abnormalities.
- Systemic arterial or venous thrombotic or embolic events within 6 months of first dose.
- History of acute or chronic pancreatitis
- History of chronic inflammatory bowel disease or Crohn's disease requiring intervention within 12 months of first dose.
- Gastrointestinal abnormalities including but not limited to:
- inability to take oral medication,
- malabsorption syndromes
About this study
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)
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).
- Conditions
- Gastrointestinal Stromal Tumors
- Being tested
- Ripretinib, binimetinib
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RipretinibDrug
Also called DCC-2618, QINLOCK
50 mg tablets
binimetinibDrug
Also called Mektovi
15 mg tablets
| Study group | Role | What they receive |
|---|---|---|
| Escalation | Experimental | 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 Receives: Drug: Ripretinib; Drug: binimetinib |
| Expansion | Experimental | 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 Receives: Drug: Ripretinib; Drug: binimetinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety/tolerability of oral ripretinib in combination with binimetinib: incidence of adverse events
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).
Measured: Approximately 12 months
Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose
Measured: Approximately 12 months
Expansion Phase Only: Evaluate the objective response rate (ORR) of ripretinib in combination with binimetinib by modified RECIST
Measure ORR
Measured: Approximately 36 months
Secondary outcomes (10)
Determine the time to maximum observed concentration (tmax) profile of oral ripretinib in combination with binimetinib
Measure Tmax
Measured: 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
Determine the maximum observed concentration (Cmax) profile of oral ripretinib in combination with binimetinib
Measure Cmax
Measured: 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
Determine the minimum observed concentration (Cmin) profile of oral ripretinib in combination with binimetinib
Measure Cmin
Measured: 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
Determine the area under the concentration-time curve (AUC) profile of oral ripretinib in combination with binimetinib
Measure AUC
Measured: 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
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)
Measure ORR
Measured: Approximately 36 months
Evaluate the progression-free survival (PFS) of ripretinib in combination with binimetinib
Measure PFS
Measured: Approximately 36 months
Evaluate the overall survival (OS) of ripretinib in combination with binimetinib
Measure OS
Measured: Approximately 36 months
Evaluate the duration of response (DOR) of ripretinib in combination with binimetinib
Measure DOR
Measured: Approximately 36 months
Evaluate the clinical benefit rate (CBR) of ripretinib in combination with binimetinib
Measure CBR
Measured: Approximately 36 months
Evaluate the time to response (TTR) of ripretinib in combination with binimetinib
Measure TTR
Measured: Approximately 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2021
- Study startNov 2021 (estimated)
- Primary completionNov 2025 (estimated)
- Study completionMay 2027 (estimated)
Why it stopped: 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal Stromal TumorsStudies of the same condition, open and under way.
- More trials run by Deciphera Pharmaceuticals, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Deciphera Pharmaceuticals, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05080621
- Sponsor's protocol ID
- DCC-2618-01-008
- Status last verified
- Dec 2021
- First submitted
- 20 Sep 2021
- Last updated
- 5 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05080621
- Acronym / sponsor ID
- DCC-2618-01-008
- Conditions
- Gastrointestinal Stromal Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: 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.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Deciphera Pharmaceuticals, LLCIndustry (pharma, biotech, devices)
- Study start
- Nov 2021 (estimated)
- Primary completion
- Nov 2025 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 18 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Escalation | Experimental | Drug: Ripretinib, Drug: binimetinibEscalation 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 |
| Expansion | Experimental | Drug: Ripretinib, Drug: binimetinibRipretinib 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients ≥18 years of age with advanced GIST (unresectable or metastatic).
- Must have at least progressed on imatinib or have documented intolerance to imatinib.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Patients must have a histologic diagnosis of GIST.
- If a female of childbearing potential, must have a negative pregnancy test.
Key exclusion criteria (14 listed)
- Received prior anticancer therapy within 14 days or 5× the half-life whichever is longer) prior to the first dose.
- Ongoing or prior participation in the DCC-2618-03-002 study.
- Prior therapy with ripretinib.
- Prior therapy with MEK inhibitor.
- History of certain ocular disorders.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RipretinibAlso: DCC-2618, QINLOCK50 mg tablets | Drug | Escalation, Expansion |
| binimetinibAlso: Mektovi15 mg tablets | Drug | Escalation, Expansion |
Primary outcome
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).
Determination of the Maximum Tolerated Dose and the Recommended Phase 2 Dose
Time frame: Approximately 12 months
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
10 secondary outcomes
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
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
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
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
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
Evaluate the progression-free survival (PFS) of ripretinib in combination with binimetinib
Time frame: Approximately 36 months
Evaluate the overall survival (OS) of ripretinib in combination with binimetinib
Time frame: Approximately 36 months
Evaluate the duration of response (DOR) of ripretinib in combination with binimetinib
Time frame: Approximately 36 months
Evaluate the clinical benefit rate (CBR) of ripretinib in combination with binimetinib
Time frame: Approximately 36 months
Evaluate the time to response (TTR) of ripretinib in combination with binimetinib
Time frame: Approximately 36 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ripretinib and binimetinib in people with Gastrointestinal Stromal Tumors, run by Deciphera Pharmaceuticals, LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety/tolerability of oral ripretinib in combination with binimetinib: incidence of adverse events (time frame: Approximately 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2022.