A phase Ib/II study of LEE011 in combination with MEK162 in patients with NRAS mutant melanoma

Phase 1

• Conditions: locally advanced or metastatic NRAS mutant melanoma; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-004104-35-NL
• Lead Sponsor: Array BioPharma Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07-18
• Last Update Posted: 30 April 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

-- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
- 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:
a. Bone marrow:
• Absolute Neutrophil Count (ANC) = 1.5 x 10E9/L
• Hemoglobin (Hgb) = 9 g/dL
• Platelets = 75 x 10E9/L without transfusions within 21 days before 1st treatment
• PT/INR and aPTT = 1.5 ULN.
b. Serum creatinine =1.5 ULN
c. Hepatic function:
•Serum total bilirubin = 1.5 x upper limit of normal (ULN)
• 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
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 68
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion Criteria

-Presence of any brain metastases detected by MRI or CT with i.v. contrast of the brain at screening.
- Uncontrolled arterial hypertension despite medical treatment - Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
a. Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO)
b. Congenital long QT syndrome or family history of unexpected sudden cardiac death
c. QTc corrected with Frederica's or Bazett's formula (QTcF) >450 ms for males and >470 ms for females on screening ECG
d. Angina pectoris = 3 months prior to starting study drug, acute myocardial infarction = 3 months prior to starting study drug, clinically significant resting bradycardia, history or presence of ventricular tachyarrhythmia, unstable atrial fibrillation (ventricular response >100 bpm), complete left bundle branch block, right bundle, branch block and left
anterior hemi block bifascicular block), obligate use of a cardiac pacemaker or implantable cardioverter defibrillator and any other clinically significant heart disease.
- Patients who are currently receiving treatment with agents that are metabolized predominantly through CYP3A4 and that have a narrow therapeutic window. Agents that are known strong inducers or inhibitors CYP3A4 are
prohibited.
- Patients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (e.g., uncontrolled diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
- History or current evidence of retinal vein occlusion RVO) or curent risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
Other, protocol related exclusion criteria may apply.

Study & Design

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