Locally Advanced or Metastatic BRAF Mutant Melanoma Clinical Trial
Official title:
A Phase Ib/II, Multicenter, Study of LEE011 in Combination With LGX818 in Adult Patients With BRAF Mutant Melanoma.
| Verified date | February 2016 |
| Source | Array BioPharma |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
To evaluate the safety, tolerability and efficacy of LEE011 and LGX818 when administered orally to patients with BRAF mutant melanoma.
| Status | Completed |
| Enrollment | 28 |
| Est. completion date | April 2015 |
| Est. primary completion date | April 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Australia | Novartis Investigative Site | Westmead | New South Wales |
| Australia | Novartis Investigative Site | Woodville | South Australia |
| Canada | Novartis Investigative Site | Montreal | Quebec |
| Netherlands | Novartis Investigative Site | Utrecht | |
| United States | University of Colorado Dept of Oncology | Aurora | Colorado |
| United States | Karmanos Cancer Institute Dept of Oncology | Detroit | Michigan |
| United States | Vanderbilt University Medical Center SC - Dept of Oncology . | Nashville | Tennessee |
| United States | Memorial Sloan Kettering Cancer Center Dept Oncology | NY | New York |
| United States | Oregon Health & Science University Dept. of OHSU (3) | Portland | Oregon |
| Lead Sponsor | Collaborator |
|---|---|
| Array BioPharma |
United States, Australia, Canada, Netherlands,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Incidence of Dose Limiting Toxicities (Phase Ib) | Dose Limiting Toxicities (DLTs) during the first 28 days of the combination treatment of LEE011 and LGX818. | Cycle 1 = 28 days | Yes |
| Primary | Progression Free Survival (PFS) - Phase II Arms 1 a/b | As per RECIST v1.1. PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. | 23 months after FPFV | No |
| Primary | Objective Response Rate (ORR) - Phase II Arm 2 | As per RECIST v1.1. ORR is defined as the proportion of patients with a best overall response of complete response or partial response. | 23 months after FPFV | No |
| Secondary | Number of Adverse Events - Phase Ib/II | To assess the safety and tolerability of LEE011 and LGX818 in these patients which includes changes in hematology and chemistry values, vital signs and electrocardiograms (ECG's) assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | Approximately 23 months after FPF | Yes |
| Secondary | Number of Serious Adverse Events - Phase Ib/II | To assess the safety and tolerability of LEE011 and LGX818 in patients which includes changes in hematology and chemistry values, vital signs and ECGs assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | Approximately 23 months after FPFV | Yes |
| Secondary | Plasma concentration-time profiles - Phase Ib/II | Plasma PK parameters of LEE011 and plasma PK parameters of LGX818. Phase 1b: Cycle 1/Days 1, 2, 8, 15, 21 and 22; Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). Phase 2: Cycle 1/Days 1, 8, 15, and 21. Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). | 28-day cycles | No |
| Secondary | Overall Response Rate (ORR) - Phase Ib and Phase II arms 1a/b | ORR is defined as the proportion of patients with a best overall response of complete response or partial response. | Approximately 23 months after FPFV | No |
| Secondary | Progression Free Survival (PFS) - Phase Ib and Phase II Arm 2 | PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. | Approximately 23 months after FPFV | No |
| Secondary | Duration Of Response (DOR) - Phase Ib, Phase II arms 1a/1b/2 | DOR is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer. | Approximately 23 months after FPFV | No |
| Secondary | Overall Survival (OS) - Phase II arms 1a/1b/2 | OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive. | Approximately 23 months after FPFV | No |
| Secondary | Plasma concentration-time profiles: AUCtau - Phase Ib/II | Plasma PK parameters of LEE011 and plasma PK parameters of LGX818. Phase 1b: Cycle 1/Days 1, 2, 8, 15, 21 and 22; Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). Phase 2: Cycle 1/Days 1, 8, 15, and 21. Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). | 28-day cycles | No |
| Secondary | Plasma concentration-time profiles: Cmin - Phase Ib/II | Plasma PK parameters of LEE011 and plasma PK parameters of LGX818. Phase 1b: Cycle 1/Days 1, 2, 8, 15, 21 and 22; Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). Phase 2: Cycle 1/Days 1, 8, 15, and 21. Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). | 28-day cycles | No |
| Secondary | Plasma concentration-time profiles: Cmax - Phase Ib/II | Plasma PK parameters of LEE011 and plasma PK parameters of LGX818. Phase 1b: Cycle 1/Days 1, 2, 8, 15, 21 and 22; Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). Phase 2: Cycle 1/Days 1, 8, 15, and 21. Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). | 28-day cycles | No |
| Secondary | Plasma concentration-time profiles: Tmax - Phase Ib/II | Plasma PK parameters of LEE011 and plasma PK parameters of LGX818. Phase 1b: Cycle 1/Days 1, 2, 8, 15, 21 and 22; Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). Phase 2: Cycle 1/Days 1, 8, 15, and 21. Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). | 28-day cycles | No |
| Secondary | Plasma concentration-time profiles: Racc - Phase Ib/II | Plasma PK parameters of LEE011 and plasma PK parameters of LGX818. Phase 1b: Cycle 1/Days 1, 2, 8, 15, 21 and 22; Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). Phase 2: Cycle 1/Days 1, 8, 15, and 21. Cycles 2, 3, 4, 5, and 6 on Day 1 of each cycle (if applicable). | 28-day cycles | No |