E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic or Unresectable NRAS Mutation-positive Melanoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027481 |
E.1.2 | Term | Metastatic melanoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 β 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
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E.4 | Principal 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 by a positive hCG laboratory test; 19. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are • women whose sexual orientation precludes intercourse with a male partner • women whose partners have been sterilized by vasectomy or other means • using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs); periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable) 20. Sexually active males unless they use a condom during intercourse while taking the drug and for 15 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid; 21. Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study.
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E.5 End points |
E.5.1 | Primary end point(s) | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |