MEK162 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)
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|ClinicalTrials.gov Identifier: NCT01991379|
Recruitment Status : Recruiting
First Posted : November 25, 2013
Last Update Posted : March 23, 2018
The purpose of this study is to evaluate the effects, good and/or bad, of MEK162 and imatinib on the patient and on Gastrointestinal Stromal Tumor (GIST).
Funding Source - FDA OOPD
|Condition or disease||Intervention/treatment||Phase|
|Gastrointestinal Stromal Tumor (GIST)||Drug: MEK162 Drug: Imatinib Mesylate (Gleevec®; STI571; NSC #716051) Other: Blood draws Procedure: biopsy||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||62 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib/II Study of MEK162 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)|
|Study Start Date :||November 2013|
|Estimated Primary Completion Date :||November 2021|
|Estimated Study Completion Date :||November 2021|
Experimental: MEK162 in Combination With Imatinib Mesylate
Pts will be treated with the combination therapy of MEK162 & imatinib. The phase Ib portion of the study, pts will receive imatinib at 400 mg once daily & MEK162 at the standard 3+3 escalation doses. Phase Ib expansion cohort, pts will receive the RP2D: imatinib 400 mg once daily (standard of care first line imatinib dose) & MEK162 at the RP2D twice daily. The phase II portion of the study, pts will receive imatinib at 400 mg once daily & MEK162 at the RP2D. The MEK162 RP2D was originally determined based on the phase Ib escalation data & it was established as 45 mg BID. After the completion of the phase Ib dose expansion & initiation of phase II, the MEK162 RP2D was reduced to 30 mg BID30 for better long term tolerability. Patient's will now begin MEK162 at the revised RP2D of 30 mg BID. 1 cycle is 28 days. If no progression of the tumor is seen, pts will continue on therapy. Pts who have progression of disease will proceed directly to second line therapy as per standard of care.
Patients should take the study drug with a glass of water. MEK162 can be taken with or without food.Drug: Imatinib Mesylate (Gleevec®; STI571; NSC #716051) Other: Blood draws Procedure: biopsy
Following informed consent, the first 20 mandatory patients, except for patients who have already been treated with imatinib prior to consent, and subsequent voluntary patients enrolled on the phase II portion of the trial will undergo research biopsies. Patients should hold both imatinib and MEK162 doses on the day they undergo a biopsy.
- maximum tolerated dose (MTD) (phase 1b portion) [ Time Frame: 1 year ]The first three patients will be enrolled at Dose Level 1. If dose level 1 is not found to be tolerable, then the next cohort will be enrolled at dose level -1. If dose level -1 is not found to be tolerable, then the study may be terminated based on discussions with the sponsor and the combination may be deemed intolerable. If 0/3 patients or 1/6 patients experience a DLT on dose level 2, this will be the RP2D.
- Best Response Rate (phase II portion) [ Time Frame: 2 years ]Response Rate (CR+PR, RECIST 1.1). Response rate (RECIST 1.1) will be determined as the proportion of evaluable patients who have complete response or partial response defined by the RECIST 1.1.
- Response Rate (RR) (phase 1b portion) [ Time Frame: 1 year ]defined by RECIST 1.1 criteria and by CHOI criteria RR will be estimated as the proportion of patients who have complete response or partial response for each criterion.
- Progression Free Survival (PFS) [ Time Frame: 1 year ]PFS will be calculated using Kaplan-Meier estimate among all patients enrolled. Patients who have not experienced the event of interest by the end of the study will be censored at the time of the last follow-up.
- RR by CHOI criteria (phase II portion) [ Time Frame: 1 year ]It will be determined as the proportion of patients who have complete response or partial response defined by the CHOI criteria with a two-sided 95% CI provided.
- RR by EORTC criteria [ Time Frame: 1 year ]It will be determined as the proportion of patients who have complete response or partial response defined by the EORTC criteria with a two-sided 95% CI provided.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01991379
|Contact: Ping Chi, MD PhD||646-888-4166|
|Contact: William Tap, MD||646-888-4163|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Ping Chi, MD 646-888-4166|
|Contact: William Tap, MD 646-888-4163|
|Principal Investigator: Ping Chi, MD, PhD|
|Principal Investigator:||Ping Chi, MD, PhD||Memorial Sloan Kettering Cancer Center|