Study comparing the efficacy of MEK162 versus dacarbazine in unresectable or metastatic NRAS mutation-positive melanoma (NEMO)

Phase 1

• Conditions: metastatic or unresectable cutaneous melanoma; MedDRA version: 20.0Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-003593-51-ES
• Lead Sponsor: Array Biopharma Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-03-06
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 393

Inclusion Criteria

Written informed consent must be obtained prior to any study procedures.
1.Signed written informed consent;
2.Male or female patient, age ? 18 years;
3.Histologically confirmed diagnosis of locally advanced, unresectable or metastatic cutaneous OR UNKNOWN PRIMARY melanoma AJCC Stage IIIC or IV UVEAL AND MUCOSAL MELANOMA ARE EXCLUDED;
4.Presence of NRAS Q61 mutation in tumor tissue prior to randomization, as determined by a Novartis designated central laboratory;
5.Naïve untreated patients or patients who have progressed on or after prior (first-line) TREATMENT WITH ANY NUMBER OF LINES OF immunotherapy for metastatic melanoma;
Note: Prior adjuvant therapy is permitted, except the administration of MEK inhibitors
6.Evidence of at least one measurable lesion as documented by radiological or photographic methods according to Novartis guideline version 3.1 based on RECIST version 1.1 (Appendix 2);
Note: A previously irradiated lesion is eligible to be considered as a measurable lesion provided that there is objective evidence of progression of the lesion since discontinuation of therapy and prior to starting study drug (see Appendix 2).
7.ECOG performance status of 0-1 (Table 7-3);
8.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); patients with liver metastases ? 5 ×ULN,
?Total bilirubin ? 2 × ULN,
?Creatinine ? 1.5 mg/dL;
9.Adequate cardiac function:
?left ventricular ejection fraction (LVEF) ? 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram,
?QTcF interval ? 480 ms;
10.Able to take oral medications;
11.Patient is deemed by the Investigator to have the initiative and means to be compliant with the protocol (treatment and follow-up);
12.Negative serum ? HCG test (female patient of childbearing potential only) performed locally within 72 hours prior to first dose.
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 295
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 98

Exclusion Criteria

1.Any UNTREATED active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions). However, patient treated with radiotherapy or surgery are eligible if the patient remained without evidence of CNS disease progression ? 4 weeks. Patients must be off corticosteroid therapy for ? 3 weeks.
2.UVEAL OR MUCOSAL MELANOMA(Non-cutaneous melanoma;)
3.History of leptomeningeal metastases;
4.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);
6.History of allogeneic bone marrow transplantation or organ transplantation;
7.History of Gilbert?s syndrome;
8.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 in complete remission for ?5 years;
9.Prior therapy with a MEK- inhibitor;
10.Patients who have received more than one line of immunotherapy for metastatic melanoma;
11.Patients with washout period < 6 weeks from the last dose of ipilimumab or other immunotherapy;
Note: chemotherapy given as part of isolated limb perfusion, regional or intralesional treatment will not be considered systemic treatment
12.Any previous systemic chemotherapy for unresectable locally advanced or metastatic melanoma;
13.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, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality <6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia;
14.Uncontrolled arterial hypertension despite medical treatment;
15.Known positive serology for HIV, active hepatitis B, and/or active hepatitis C infection
16.Patients who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy);
17.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;
18.Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection);
19.Any other condition that would, in the Investigator?s judgment, contraindicate the patient?s participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.;
20.Patients who have undergone major surgery or radiotherapy ? 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure;
21.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified