Clinical trial NCT01777776: Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.
Official title: A Phase Ib/II, Multicenter, Study of LEE011 in Combination With LGX818 in Adult Patients With BRAF Mutant Melanoma.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Locally Advanced Metastatic BRAF Mutant Melanoma
Keywords: Open-label dose escalation
BRAF inhibitor
LEE011
CDK4/6
LGX818
RAF kinase inhibitor
Metastatic melanoma
BRAF
V600
Lead sponsor: Array BioPharma
Sponsor class: INDUSTRY
First posted: 2013-01-29
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
timeFrame: Cycle 1 (approximately 28 days)
measure: Phase II - Progression Free Survival (PFS)
timeFrame: Approximately 23 months after enrollment
measure: Phase II - Objective Response Rate (ORR)
timeFrame: Approximately 23 months after enrollment
Secondary outcomes:
measure: Phase I - Number of Subjects Experiencing at Least One Adverse Event (AE).
timeFrame: Approximately 23 months after enrollment
measure: Phase I - Number of Subjects Experiencing at Least One Serious Adverse Event (SAE).
timeFrame: Approximately 23 months after enrollment
measure: Phase Ib/II - Plasma Concentration-time Profiles
timeFrame: 28-day cycles
measure: Phase Ib/II - Overall Response Rate (ORR)
timeFrame: Approximately 23 months after enrollment
measure: Phase Ib/II - Progression Free Survival (PFS)
timeFrame: Approximately 23 months after enrollment
measure: Phase Ib/II - Duration Of Response (DOR)
timeFrame: Approximately 23 months after enrollment
measure: Phase II - Overall Survival (OS)
timeFrame: Approximately 23 months after enrollment
measure: Phase Ib/II - Pharmacokinetic Parameters: AUCtau
timeFrame: 28-day cycles
measure: Phase Ib/II - Pharmacokinetic Parameters: Cmin
timeFrame: 28-day cycles
measure: Phase Ib/II - Pharmacokinetic Parameters: Cmax
timeFrame: 28-day cycles
measure: Phase Ib/II - Pharmacokinetic Parameters: Tmax
timeFrame: 28-day cycles
measure: Phase Ib/II - Pharmacokinetic Parameters: Racc
timeFrame: 28-day cycles
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Dept of Oncology
state: Colorado
city: Detroit
country: United States
facility: Karmanos Cancer Institute Dept of Oncology
state: Michigan
city: NY
country: United States
facility: Memorial Sloan Kettering Cancer Center Dept Oncology
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University Dept. of OHSU (3)
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University Medical Center SC - Dept of Oncology .
state: Tennessee
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Woodville
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
Study officials:
affiliation: 303-381-6604
name: Array BioPharma
role: STUDY_DIRECTOR
References: