Binimetinib and Imatinib for Unresectable Stage III-IV KIT-Mutant Melanoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04598009|
Recruitment Status : Recruiting
First Posted : October 22, 2020
Last Update Posted : December 20, 2021
|Condition or disease||Intervention/treatment||Phase|
|Melanoma Stage III Melanoma Stage IV||Drug: Binimetinib Drug: Imatinib||Phase 2|
I. To evaluate the overall response rate (ORR) of binimetinib plus imatinib in patients with advanced KIT-mutant melanoma.
I. To determine the safety and tolerability of binimetinib plus imatinib in patients with advanced KIT-mutant melanoma.
II. To estimate efficacy and survival parameters in patients with advanced KIT-mutant melanoma treated with binimetinib plus imatinib.
III. To estimate efficacy in patients with advanced KIT-mutant melanoma treated with binimetinib plus imatinib.
I. To investigate association between changes in drug phosphorylated end products (p-KIT, p-MEK, p-ERK) and clinical response.
II. To investigate association between clinical response and baseline Neurofibromatosis 1 (NF1) and SPRED1 status.
III. To investigate pathologic correlates of acquired resistance. IV. To investigate whether NF1 and SPRED1 loss contribute to acquired resistance.
V. To generate patient-derived xenograft models. VI. To determine the relationship between clinical outcomes and clinicopathologic features including KIT exon mutated, melanoma subtype, melanoma primary site, race/ethnicity, prior treatment history including immune checkpoint inhibitor (ICI)-experienced versus (vs) - naive.
Patients receive binimetinib orally (PO) twice daily (BID) on days 1-28 and imatinib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at day 30 and 100, and then every 3 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Binimetinib in Combination With Imatinib in Patients With Advanced KIT-Mutant Melanoma|
|Actual Study Start Date :||March 3, 2021|
|Estimated Primary Completion Date :||July 31, 2023|
|Estimated Study Completion Date :||March 31, 2025|
Experimental: Treatment (binimetinib, imatinib)
Patients receive binimetinib PO BID on days 1-28 and imatinib PO QD on days 1-28. Cycles repeat every 28 days
Taken orally (PO) twice a day (BID)
Taken orally (PO) once a day (QD)
Other Name: Imatinib Mesylate
- Objective response rate (ORR) [ Time Frame: Up to week 16 ]Defined as complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The ORR at stages 1 and 2 will be estimated using the method of Whitehead, and the p-values for testing the null hypothesis at each stage will use the method of Koyama & Chen and 90% confidence interval will be reported.
- Proportion of participants with treatment-related adverse events (AE) [ Time Frame: Up to 2 years ]Proportion of participants with treatment-related AEs greater than grad2 as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 will be reported by toxicity.
- Median duration of response [ Time Frame: Up to 2 years ]Will estimate the probability-of-being-in-response function, assuming time to response is exponentially distributed.
- Progression-free survival (PFS) [ Time Frame: Up to 2 years ]Participants with an objective response will be followed for survival from initiation of study treatment until date of disease progression or death from any cause
- Overall survival (OS) [ Time Frame: Up to 2 years ]Participants will be followed from initiation of study treatment until date of disease progression or death from any cause and estimated using the Kaplan-Meier method to estimate the survival rate (95% CI)
- Clinical benefit rate (CBR) [ Time Frame: Up to 2 years ]Defined as CR, PR, or stable disease (SD) >= 16 weeks by RECIST. CBR will be defined as the proportion of participants with CR, PR, or SD for >= 16 weeks.
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): NCT04598009
|Contact: Ari Olglesby Persaud||(415) email@example.com|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Ari Oglesby Persaud 415-885-7399 firstname.lastname@example.org|
|Contact 877-827-3222 email@example.com|
|Principal Investigator: Katy Tsai, MD|
|Principal Investigator:||Katy Tsai, MD||University of California, San Francisco|