Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.

NCT ID: NCT01777776

Last Updated: 2016-09-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2015-04-30

Brief Summary

To evaluate the safety, tolerability and efficacy of LEE011 and LGX818 when administered orally to patients with BRAF mutant melanoma.

Detailed Description

In response to developments in the treatment of melanoma, the sponsor reviewed the data from the ongoing study and decided to halt further enrollment of patients in the Phase Ib part of the study. Consequently, the Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns.

Conditions

Locally Advanced Metastatic BRAF Mutant Melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase Ib

Phase Ib will randomize 18 patients with BRAF mutant melanoma, who are naïve or who have progressed on prior therapy to evaluate the safety and tolerability of the combination of LEE011 and LGX818.

Group Type: EXPERIMENTAL

LEE011

Intervention Type: DRUG

LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818

Intervention Type: DRUG

LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).

Phase II arm 1a

Phase II arm 1a will randomize 60 patients that are naïve to prior BRAF inhibitor therapy to LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.

Group Type: EXPERIMENTAL

LEE011

Intervention Type: DRUG

LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818

Intervention Type: DRUG

LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).

Phase II arm 1b

Phase II arm 1b will randomize 30 patients to LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.

Group Type: EXPERIMENTAL

LGX818

Intervention Type: DRUG

LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).

Phase II arm 2

Phase II arm 2 will evaluate a single arm LEE011+LGX818 in 40 patients resistant to prior BRAF inhibitor therapy. Single agent LGX818 has shown limited activity in patients with melanoma who have failed prior BRAF inhibitor treatment; the contribution of LEE011 in this combination will be evaluated.

Group Type: EXPERIMENTAL

LEE011

Intervention Type: DRUG

LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

LGX818

Intervention Type: DRUG

LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).

Interventions

LEE011

LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).

Intervention Type: DRUG

LGX818

LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).

Intervention Type: DRUG

Other Intervention Names

Ribociclib; Encorafenib

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years.
• Diagnosis of locally advanced or metastatic melanoma along with written documentation of BRAF V600 mutation.
• ECOG performance status of 0 - 2.
• Patients enrolled into Phase Ib must have evidence of evaluable and/or measurable disease as determined by RECIST v1.1.
• Patients enrolled into Phase II (BRAFi naïve and resistant) must have evidence of measurable disease as determined by RECIST v1.1.
• Archival tumor tissue must be obtained for patients enrolled in Phase Ib and Phase II arm 1a/b- BRAFi naïve patients. If an archival tumor tissue is not available, a fresh tumor sample is acceptable.
• For patients enrolled in the phase II arm 2, patients must agree to undergo a fresh tumor biopsy unless one was collected prior to study entry but at the time of disease relapse from the most recent BRAFi treatment.

Exclusion Criteria

• Symptomatic brain metastases.
• Symptomatic or untreated leptomeningeal disease.
• Patients with inadequate laboratory values during screening.
• In the phase II BRAFi naïve arms (1a/b), prior exposure to CDK4/6 inhibitor (e.g., PD 0332991)
• Impaired cardiac function or clinically significant cardiac diseases.
• Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of LEE011 or LGX818.
• Patients with concurrent severe and/or uncontrolled concurrent medical conditions.
• Previous or concurrent malignancy.
• Major surgery < 2 weeks before starting study treatment
• Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Array BioPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Array BioPharma

Role: STUDY_DIRECTOR

303-381-6604

Locations

University of Colorado Dept of Oncology

Aurora, Colorado, United States

Karmanos Cancer Institute Dept of Oncology

Detroit, Michigan, United States

Memorial Sloan Kettering Cancer Center Dept Oncology

New York, New York, United States

Oregon Health & Science University Dept. of OHSU (3)

Portland, Oregon, United States

Vanderbilt University Medical Center SC - Dept of Oncology .

Nashville, Tennessee, United States

Novartis Investigative Site

Westmead, New South Wales, Australia

Novartis Investigative Site

Woodville, South Australia, Australia

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Utrecht, Netherlands, Netherlands

Countries

United States; Australia; Canada; Netherlands

Other Identifiers

CLEE011X2105

Identifier Type: -

Identifier Source: org_study_id