Metastatic or Unresectable NRAS Mutation-positive Melanoma MedDRA version: 16.1 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: MEK162
Pharmaceutical Form: Film-coated tablet
CAS Number: 606143-89-9
Current Sponsor code: MEK162
Other descriptive name: MEK162
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Uzsoki Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for inclusion in this Treatment Plan have to meet all of the following criteria: Written informed consent must be obtained prior to any screening procedures or treatment assignment. 1. Signed written informed consent; 2. Male or female patient, age = 18 years; 3. Histologically confirmed diagnosis of locally advanced, unressectable or metastatic cutaneous melanoma AJCC Stage IIIC or IV; 4. Presence of activating mutations of RAS oncogenes in tumor tissue prior to randomization as determined by a validated method. 5. Adequate bone marrow, organ function and laboratory parameters: • Absolute neutrophil count (ANC) = 1.5 x 109/L, • Hemoglobin (Hgb) = 10 g/dL without transfusions, • Platelets (PLT) = 100 x 109/L without transfusions, • AST and/or ALT = 2.5 × upper limit of normal (ULN); patient with liver metastases = 5 ×ULN, • Total bilirubin = 2 × ULN, • Creatinine = 1.5 mg/dL; 6. Adequate cardiac function: • left ventricular ejection fraction (LVEF) = 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram, • QTc interval = 480 ms; 7. Able to take oral medications; 8. Patient is deemed by the Investigator to have the initiative and means to be compliant with the treatment plan (treatment and follow-up requested by the treating physician); 9. Negative serum ß HCG test (female patient of childbearing potential only) performed locally within 72 hours prior to first dose. 10. Has failed available standard of care treatment options or is highly unlikely, due to their disease characteristics, to respond to the available standard of care treatment options. 11. Is not eligible for participation in any MEK162 ongoing clinical trials or has recently completed a clinical trial that has been terminated and, after considering other options (e.g., trial extensions, amendments, etc.), the clinical team has determined that treatment is necessary and there are no other feasible alternatives for the patient 12. Is not being transferred from an ongoing clinical trial for which they are still eligible Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Patients eligible for this Treatment Plan must not meet any of the following criteria: 1. History of hypersensitivity to any drugs or metabolites of similar chemical classes as MEK162. 2. Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions). However, patient treated with stereotactic radiotherapy, surgery or whole-brain radiation are eligible if the patient remained without evidence of CNS disease progression = 3 months. Patients must be off corticosteroid therapy for = 3 weeks; 3. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); 4. History of retinal degenerative disease; 5. History of Gilbert’s syndrome; 6. Previous or concurrent malignancy with the following exceptions: • adequately treated basal cell or squamous cell carcinoma of the skin (adequate wound healing is required prior to study entry), • in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to the study, • a primary malignancy which has been completely resected and is in complete remission for =5 years; 7. Prior therapy with a MEK- inhibitor; 8. Concomitant use of any anticancer agent (chemotherapy, immunotherapy or targeted agents); 9. Prior participation during the NEMO Study (even if the patient was randomized to receive DTIC); 10. Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) <6 months prior to screening, • Symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia; 11. Uncontrolled arterial hypertension despite appropriate medical therapy; 12. Known positive serology for HIV, active hepatitis B, and/or active hepatitis C infection; 13. Patients who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy); 14. Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment. NB: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment; 15. Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection); 16. Any other condition that would, in the treating physician’s judgment, contraindicate the patient’s participation in this compassionate use program due to safety concerns or compliance with treatment procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.; 17. Patients who have undergone major surgery = 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure; 18. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed b
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Prospective, mono-center study the efficacy and safety of MEK162 (45 mg BID) in previously pretreated patients with advanced (Stage IIIC) unresectable or metastatic (Stage IV) cutaneous melanoma with mutant RAS. This study is being done: 1) to allow patients who would otherwise not to be able to access MEK162 treatment in an ongoing phase III MEK162 study, 2) to further describe the side effects of MEK162, 3) to determine if a patient's tumor gets smaller according to the treatment with MEK162.;Secondary Objective: ;Primary end point(s): | — |
Countries
Hungary
Outcome results
None listed