Clinical Trial VICCMEL1310
A Phase Ib/II, Multicenter, Open Label, Study of LEE011 in Combination with MEK162 in Adult Patients with NRAS Mutant Melanoma
- Protocol No. VICCMEL1310
- Open Date: 06/17/2013
- Staging: Phase I/II
- Age Group: Adults
- Scope: National
- Objective: Phase Ib - Determine the Maximum Tolerated Dose(s) (MTD(s)) and/or Recommended Phase II Dose (RP2D) of LEE011 and MEK162 in combination Phase II - Assess the anti-tumor activity of the LEE011 and MEK162 combination at the RP2D
- Disease Sites: Melanoma
- Therapies: Molecular Targeted Agents / Immunotherapy / Biologics
- Drugs: LEE011; MEK 162
- Participating Institutions: Vanderbilt University
- National Clinical Trial ID: NCT01781572
- Secondary Protocol No: CMEK162X2114
Participants are being asked to take part in this research study because they have melanoma (a type of skin cancer) and because their cancer has returned or worsened and cannot be cured by any standard treatment. The purpose of this study is to find the highest dose of LEE011 in combination with MEK162 that we can give safely in adults with certain cancers and furthermore, evaluate any changes in tumor size. This study will evaluate the effects of the combination of the two drugs, LEE011 and MEK162, in melanoma (skin cancer), carrying a specific alteration (also called mutated) in a gene called NRAS. The changes in NRAS gene may lead to cancer growth. This study will help to assess if patients with NRAS changes may be more responsive to LEE011 and MEK162 treatment.
|Ages Eligible for Study:||18 Years and older|
|Genders Eligible for Study:||Both|
|Accepts Healthy Volunteers:||No|
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0•2
• Patients enrolled into phase Ib may be enrolled with evaluable disease only. Patients enrolled into the phase II expansion must have at least one measurable lesion as defined by RECIST 1.1 criteria.
• Patients must have adequate organ function, as defined by the following parameters:
1. Bone marrow:
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dL
• Platelets ≥ 75 x 109/L without transfusions within 21 days before 1st treatment
2. Serum creatinine ≤1.5 ULN
3. Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)
4. Aspartate Aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and ALT (SGPT) ≤ 3 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ≤ 5 x ULN
• Symptomatic brain metastases. Patients previously treated or untreated for brain metastases that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastases must be stable for at least 2 weeks after completion of the definitive therapy with verification by imaging (e.g. brain MRI completed at screening demonstrating no current evidence of progressive brain metastases).
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
1. Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO)
2. Congenital long QT syndrome or family history of unexpected sudden cardiac death
3. QTc corrected with Frederica's or Bazett's formula (QTcF) >450 ms for males and >470 ms for females on screening ECG
4. Any other clinically significant heart disease such as angina pectoris, resting bradycardia, left bundle branch block, ventricular tachyarrhythmia, unstable atrial fibrillation, branch block or hemi block, acute myocardial infarction or any heart disease that requires the use of a cardiac pacemaker or implantable cardioverter defibrillator
• Patients who are currently receiving treatment with agents that are known to cause QTc prolongation in humans. See investigators brochure for a complete list of agents that are known to cause QTc prolongation in humans.
• Patients who are currently receiving treatment with agents that are metabolized predominantly through CYP3A4 and that have a narrow therapeutic window.
• Patients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., uncontrolled hypertension and/or diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
• Current evidence of retinal disease; history of CSR, RVO or ophthalmology as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO (e.g., optic disc cupping, visual field defects, IOP > 21 mm Hg)
Other protocol related inclusion/exclusion criteria may apply.