Binimetinib and Imatinib for Unresectable Stage III-IV KIT-Mutant Melanoma
- Conditions
- Melanoma Stage IIIMelanoma Stage IV
- Registration Number
- NCT04598009
- Lead Sponsor
- University of California, San Francisco
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br> - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)<br><br> - Have histologically or cytologically confirmed melanoma<br><br> - Have unresectable Stage III or Stage IV melanoma, as per American Joint Committee on<br> Cancer 8th edition guidelines, not amenable to local therapy<br><br> - Have measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1<br> (RECIST v1.1) criteria<br><br> - Have documentation of KIT-mutant melanoma by Clinical Laboratory Improvement Act<br> (CLIA)-certified testing platform<br><br> - Participants have progressed on prior standard-of-care therapy, or would be<br> ineligible for or unable to tolerate standard-of-care therapy, in the opinion of the<br> treating Investigator<br><br> - For participants who have received prior ICI, the following is permitted:<br><br> - Prior adjuvant or neoadjuvant ICI, if last dose administered at least 4 weeks<br> prior to study drug start<br><br> - Prior ICI for the treatment of unresectable/metastatic disease, if last dose<br> administered at least 4 weeks prior to study drug start<br><br> - Absolute neutrophil count >= 1,500/microliter (mcL)<br><br> - Platelets >= 100,000/mcL<br><br> - Total bilirubin below normal institutional limits, unless elevated due to Gilbert's<br> syndrome and direct bilirubin is within normal limits<br><br> - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) =<<br> 3 x institutional upper limit of normal<br><br> - Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)) =< 3 x<br> institutional upper limit of normal<br><br> - Creatinine =< 1.5 x within institutional upper limit of normal OR creatinine<br> clearance glomerular filtration rate (GFR) >= 50 mL/min calculated using the<br> Cockcroft-Gault formula<br><br> - Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral<br> therapy, with undetectable viral load within 3 months of study drug start, are<br> eligible for this trial<br><br> - For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV<br> viral load must be undetectable on suppressive therapy, if indicated<br><br> - Individuals with a history of hepatitis C virus (HCV) infection must have been<br> treated and cured. For individuals with HCV infection who are currently on<br> treatment, they are eligible if they have an undetectable HCV viral load<br><br> - Individuals with new or progressive brain metastases (active brain metastases) or<br> leptomeningeal disease are eligible if the treating physician determines that<br> immediate central nervous system (CNS)-specific treatment is not required prior to<br> study start<br><br> - Individuals with a prior or concurrent malignancy whose natural history or treatment<br> does not have the potential to interfere with the safety or efficacy assessment of<br> the investigational regimen are eligible for this trial<br><br> - Imatinib and/or binimetinib may have teratogenic effects. Women of child-bearing<br> potential (WOCBP) must agree to:<br><br> - Use highly effective contraception to avoid pregnancy from screening through 30<br> days after the last dose of study drugs;<br><br> - Refrain from donating ova during the study through 30 days after the end of<br> systemic exposure to study drugs;<br><br> - Inform her treating physician immediately should she become pregnant or suspect<br> she is pregnant while she is participating in this study<br><br> - Sexually active men enrolled on this protocol must agree to:<br><br> - Use a condom for the duration of study participation and through 90 days after<br> the end of systemic exposure to study drugs;<br><br> - Refrain from donating sperm during the study through 90 days after the end of<br> systemic exposure to study drugs;<br><br> - If the male participant has a partner that is a WOCBP, that partner should also<br> use highly effective contraception for the duration of the study and through 90<br> days after the end of the male participant's systemic exposure to study drug<br><br> - Inform his treating physician immediately should his partner become pregnant<br> while he is participating in this study<br><br>Highly effective (i.e., failure rate <1% per year when used consistently and correctly)<br>methods of contraception include:<br><br> - Complete abstinence from heterosexual intercourse<br><br> - Combined (estrogen and progesterone) hormonal contraception associated with<br> inhibition of ovulation (oral, intravaginal, transdermal)<br><br> - Progesterone-only hormonal contraception associated with inhibition of ovulation<br> (oral, injectable, implantable)<br><br> - Intra-uterine device (IUD)<br><br> - Intrauterine hormone-releasing system (IUS)<br><br> - Bilateral tubal occlusion<br><br> - Vasectomized male partner (provided the vasectomized male has received medical<br> assessment of surgical success, and that the male is a female participant's sole<br> sexual partner)<br><br> - Ability to understand a written informed consent document, and the willingness<br> to sign it<br><br> - The participant is deemed by the Investigator to have the initiative and means<br> to be compliant with scheduled visits, treatment plan, and study procedures<br><br>Exclusion Criteria:<br><br> - Has received systemic anti-cancer therapies within 3 weeks of study drug start,<br> radiation within 2 weeks, antibody therapy within 4 weeks<br><br> - Has not recovered from adverse events due to prior anti-cancer therapy to =< grade 1<br> or baseline. Note: Stable chronic conditions (grade =< 2) that are not expected to<br> resolve (such as neuropathy, myalgia, alopecia, prior therapy-related<br> endocrinopathies) are exceptions and may enroll<br><br> - Is currently receiving any other investigational agents or has received an<br> investigational agent within 14 days or within 5 half-lives of investigational agent<br> (whichever is shorter), prior to start of study drugs<br><br> - Inability to swallow and retain study drugs<br><br> - Impairment of gastrointestinal function or disease which may significantly alter the<br> absorption of study drugs (e.g., active ulcerative disease, uncontrolled vomiting or<br> diarrhea, malabsorption syndrome, complete small bowel resection), or recent (=< 3<br> months) history of a partial or complete bowel obstruction, or other conditions that<br> will interfere significantly with the absorption of oral drugs<br><br> - Hypersensitivity to binimetinib or any of its excipients<br><br> - Hypersensitivity to imatinib or any of its excipients<br><br> - Concurrent neuromuscular disorder that is associated with elevated creatinine-kinase<br> (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral<br> sclerosis, spinal muscular atrophy)<br><br> - History or current evidence of retinal vein occlusion (RVO) or current risk factors<br> for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of<br> hyperviscosity of hypercoagulability syndromes); history of retinal degenerative<br> disease<br><br> - Impaired cardiovascular function or clinically significant cardiovascular disease<br> including, but not limited to, any of the following:<br><br> - History of acute coronary syndromes (including myocardial infarction, unstable<br> angina, coronary artery bypass g
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective response rate (ORR)
- Secondary Outcome Measures
Name Time Method Proportion of participants with treatment-related adverse events (AE);Median duration of response;Progression-free survival (PFS);Overall survival (OS);Clinical benefit rate (CBR)