Binimetinib Plus Belinostat for Subjects With Metastatic Uveal Melanoma
- Conditions
- Metastatic Uveal Melanoma
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 32
Inclusion Criteria:<br><br> - Provision of signed and dated informed consent form.<br><br> - Male or female, aged >/= 18 years old<br><br> - Life expectancy of greater than 3 months in the opinion of the investigator<br><br> - Must have metastatic uveal melanoma, either initial presentation or recurrent, that<br> is histologically diagnosed<br><br> - Participant must have ECOG performance status of 0-1<br><br> - Participant must have measurable disease, according to RECIST version 1.1<br><br> - Participants must have normal organ and marrow function as defined below:<br><br> - Leukocytes >3,000/mcL<br><br> - Absolute neutrophil count >1,500/mcL<br><br> - Platelets >100,000/mcL<br><br> - Total bilirubin within 1.5 x institutional upper limit of normal<br><br> - AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal<br><br> - Creatinine within 1.5 x institutional upper limit of normal OR creatinine clearance<br> >60 mL/min/1.73 m2 for participants with creatinine levels above institutional<br> normal<br><br> - An echocardiogram should be performed at baseline in all patients. Ejection fraction<br> (EF) from baseline echocardiogram must be within the institutional limits of normal<br> as determined by the reading cardiologist. The left ventricular ejection fraction<br> (LVEF) must be =50%<br><br> - Participants on full-dose anticoagulants (e.g., warfarin) with PT INR >1.5 are<br> eligible provided that both of the following criteria are met:<br><br> - a) The participant has an in-range INR (usually between 2 and 3) on a stable dose of<br> oral anticoagulant or on a stable dose of low molecular weight heparin<br><br> - b) The participant has no active bleeding or pathological condition that carries a<br> high risk of bleeding (e.g., tumor involving major vessels or known varices)<br><br> - A participant may be treatment naïve. However, prior systemic treatments for<br> metastatic uveal melanoma are allowed. There is no limit on the number of prior<br> regimens for metastatic uveal melanoma. However, no prior therapy with a MEK<br> inhibitor or an HDAC inhibitor<br><br> - Participant must be free of active brain metastasis by contrast-enhanced CT/MRI<br> scans within 4 weeks prior to enrollment. If known to have prior brain metastases,<br> these must have been adequately managed with standard of care radiation therapy,<br> stereotactic radiosurgery or surgery prior to registration on the study<br><br> - For females of reproductive potential: use of highly effective contraception for at<br> least 1 month prior to screening and agreement to use such a method during study<br> participation and for an additional 6 months after the end of any study drug<br> administration<br><br> - For males of reproductive potential and/or with female partners of reproductive<br> potential: use of condoms or other methods to ensure effective contraception with<br> partner for 3 months after the last dose of any study drug.<br><br>Exclusion Criteria:<br><br> - Pregnancy or lactation<br><br> - Treatment with another investigational drug or other systemic intervention for uveal<br> melanoma within 4 weeks of initiation of study drugs. Participants must not have<br> radiotherapy within the preceding 4 weeks. Participants must have recovered from<br> adverse events due to agents administered more than 4 weeks earlier<br><br> - Participants must be at least 4 weeks from major surgery and have fully recovered<br> from any effects of surgery and be free of significant detectable infection<br><br> - Participants must not have other significant medical, surgical, or psychiatric<br> conditions or require any medication or treatment that in the opinion of the<br> investigator may interfere with compliance, make the administration of the study<br> drugs hazardous or obscure the interpretation of AEs<br><br> - Participants must not have an active infection requiring current treatment with<br> parenteral antibiotics<br><br> - Cardiac: No evidence of congestive heart failure, symptoms of coronary artery<br> disease, myocardial infarction less than 6 months prior to entry, serious cardiac<br> arrhythmias, or unstable angina<br><br> - CNS: No history of cerebrovascular accident or transient ischemic attacks within the<br> past 6 months<br><br> - Serious or non-healing wound, ulcer, or bone fracture<br><br> - History of abdominal fistula, gastrointestinal perforation, or intra-abdominal<br> abscess within 4 weeks of initiating study treatment<br><br> - Participants with clinically significant cardiovascular or cerebrovascular disease:<br><br> - History of cerebrovascular accident or transient ischemic attack within past 6<br> months<br><br> - Uncontrolled hypertension, defined as blood pressure >150/100 mm Hg or systolic BP<br> >180 mm Hg if diastolic blood pressure <90 mm Hg, on at least 2 repeated<br> determinations on separate days within past 3 months<br><br> - Myocardial infarction, CABG or unstable angina within the past 6 Months<br><br> - New York Heart Association grade III or greater congestive heart failure (Appendix<br> E), serious cardiac arrhythmia requiring medication, unstable angina pectoris within<br> past 6 months<br><br> - Clinically significant peripheral vascular disease within past 6 months<br><br> - Pulmonary embolism, DVT, or other thromboembolic event within past 6 months<br><br> - PT INR >1.5 unless the patient is on full-dose warfarin<br><br> - Participants who have other current malignancies are not eligible. Participants with<br> other malignancies are eligible if they have been continuously disease free for > 3<br> years prior to the time of study registration (enrollment). Participants with prior<br> history at any time of any in situ cancer, lobular carcinoma of the breast in situ,<br> cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ are<br> eligible. Participants with prior history of basal or squamous skin cancer are<br> eligible<br><br> - History of retinal vein occlusion, uveitis refractory to ocular therapy, and<br> symptomatic serous retinopathy or retinal pigment epithelial detachments<br><br> - Active requirement for or a history of corticosteroid systemic therapy in order to<br> treat Interstitial lung disease (ILD) or pneumonitis<br><br> - The presence of a disorder that may impact absorption of study drugs, such as<br> inability to take oral medication, requirement for IV alimentation, prior gastric<br> resection, treatment for active peptic ulcer confirmed by endoscopy within the past<br> 3 months, active GI bleed, GI malabsorption syndrome
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall Response Rate
- Secondary Outcome Measures
Name Time Method Progression Free Survival;Overall Survival