Radiotherapy & Combi in Metastatic Melanoma

Exclusion Criteria

• •1. Treatment with Ipilimumab or any other anti-CTLA-4 monoclonal antibody therapy within the past 4 weeks.
• •2. Treatment with anti-PD-1 or anti-PD-L1 monoclonal antibody therapy within the past 4 weeks.
• •3. Known ocular or primary mucosal melanoma.
• •4. Four (4) or more lesions requiring palliative RT at the time of study enrolment.
• •5. Symptomatic brain metastases or those treated \< 3 months previously.
• •6. Clear evidence of systemic disease progression on dabrafenib and trametinib.
• •7. Systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment) within the last 4 weeks. Prior interferon treatment in the adjuvant setting is allowed.
• •Note: Tamoxifen and aromatase inhibitors are allowed in the adjuvant setting of breast cancer.
• •8. Current use of a prohibited medication (list of prohibited medications in protocol).
• •9. History of malignancy other than disease under study within 3 years of study enrolment with exceptions below, or any malignancy with confirmed activating RAS mutation.
• •Note: Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility.
• •Exception: Subjects who have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin cancer.
• •10. Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures.
• •11. A history of known Human Immunodeficiency Virus (HIV).
• •12. A history or evidence of cardiovascular risk including any of the following:
• •* A QT interval corrected for heart rate using the Bazett's formula (QTcB) ≥ 480 msec;
• •* A history or evidence of current clinically significant uncontrolled arrhythmias;
• •* A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to enrolment;
• •* A history or evidence of current ≥ Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines;
• •* Patients with intra-cardiac defibrillators;
• •* Abnormal cardiac valve morphology (≥ grade 2) documented by echocardiogram (subjects with grade 1 abnormalities \[i.e., mild regurgitation/stenosis\] can be entered on study). Subjects with moderate valvular thickening should not be entered on study; g. Treatment refractory hypertension defined as a blood pressure of systolic\> 140 mmHg and/or diastolic \> 90 mm Hg which cannot be controlled by anti-hypertensive therapy; h. Known cardiac metastases.
• •13. A history of retinal vein occlusion (RVO).
• •14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO).
• •15. Pregnant or nursing females.
• •16. Previous RT to the same lesion or area due to receive the current course of palliative RT.
• •Note: patients who had previous RT to other areas are eligible to the study if the previous RT was completed more than 8 weeks prior.
• •17. A history of autoimmune diseases which are known to increase radiation toxicity, including systemic lupus erythematosus and scleroderma.
• •18. Genetic syndromes exhibiting increased radiosensitivity (e.g. ataxia telangiectasia).