BRAF V600 Mutation, Melanoma Stage III, Melanoma Stage IV
Conditions
Keywords
Skin
Brief summary
The purpose of this study is to assess rate of disease relapse and hazard rate of disease relapse after neoadjuvant therapy based on the statuses of pathologic complete response or non-pathologic complete response, and postoperative adjuvant therapy.
Interventions
DRUGEncorafenib Pill
Encorafenib 450 mg will be administered orally once per day in continuous 28-day cycles
DRUGBinimetinib Pill
Binimetinib 45 mg will be administered orally twice per day in continuous 28-day cycles
DRUGNivolumab
Nivolumab will be administered at a dose of 480 mg IV infusion over 30 minutes every 4 weeks.
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years at the time of informed consent * Histologically confirmed diagnosis of melanoma. Any primary or unknown origin is permitted. * Melanoma must have a BRAFV600 mutation (using a CLIA-validated assay), either stage III (B/C/D) or Stage IV (AJCC 8th edition). * ECOG performance status ≤ 2 * Adequate laboratory parameters as well: * a. Hemoglobin ≥ 8 g/dL. * b. Platelets ≥ 75 × 109/L; * c. AST and ALT ≤ 2.5 × ULN; in participants with liver metastases ≤ 5 × ULN; * d. Total bilirubin ≤ 1.5 × ULN and \< 2 mg/dL; OR total bilirubin \>1.5 × ULN with indirect bilirubin \< 1.5 × ULN; * e. Serum creatinine ≤ 2.0 × ULN * Female participants of childbearing potential as described in protocol, must have a negative serum or urine β-HCG test result. Female participants of childbearing potential must agree to use methods of contraception that are highly effective or acceptable, as described in Section 4.3.1. Participants must agree to not use hormonal contraceptives, as encorafenib can result in decreased concentration and loss of efficacy. Male participants must agree to use methods of contraception that are highly effective or acceptable per protocol.
Exclusion criteria
* Participants may have received prior therapy with BRAF and/or a MEK inhibitor if it was completed at least 6 months prior to study enrollment. Patients who had prior disease progression while on BRAF/MEK inhibitor therapy are not eligible. (Progression after stopping treatment is permitted.) Participants may have received prior therapy an anti-PD-1/PD-L1 or CTLA-4 inhibitor. * Participants must not have had adverse events related to encorafenib and/or binimetinib specifically, that required discontinuation of one or both drugs due to toxicity. * Participants who have had major surgery or radiotherapy ≤ 14 days prior to start of study treatment or who have not recovered from side effects of such procedure. * Participants must be willing to avoid consuming grapefruit, pomegranates, star fruits, Seville oranges or products containing the juice during the study while they are taking encorafenib/binimetinib. * Uncontrolled or symptomatic brain metastases or leptomeningeal carcinomatosis that are not stable, require steroids, are potentially life-threatening or have required radiation within 28 days prior to starting study drug. Patients with previously treated brain metastases may participate provided they are stable (e.g.,without evidence of progression by radiographic imaging for at least 28 days before the first dose of study treatment and neurologic symptoms have returned to baseline). * Impaired cardiovascular function as below: * a. Congestive heart failure requiring treatment (New York Heart Association Grade ≥ 3); * b. presence of uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia * c. Baseline QTcF interval ≥ 500 ms. * Known history of retinal vein occlusion (RVO) * Current use of a prohibited medication (including herbal medications, supplements, or foods), as described in protocol, or use of a prohibited medication ≤ 1 week prior to the start of study treatment. * Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 90 days prior to randomization. * Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load prior to randomization. * Pregnancy or breast feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Disease Relapse | After surgery up to 24 weeks | Investigators will estimate the rate of disease relapse after neoadjuvant therapy based on pathologic complete response status and postoperative adjuvant therapy within each arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse Free Survival | After surgery up to 24 weeks | Relapse free survival is defined as time from surgery until disease relapse |
| Rate of Pathologic Complete Response | At 26 weeks | Investigators will measure the rate of pathologic complete response after surgery. |
| Rate of Non-Pathologic Complete Response | At 26 weeks | Investigators will measure the rate of non-pathologic complete response after surgery. |
| Overall Response Rate | Up to 26 weeks | Overall response rate will be measured after neoadjuvant therapy (for participants who have measurable disease per RECIST 1.1 at start of neoadjuvant therapy). |
| Overall Survival | After surgery, up to 5 years | Overall survival will be measured from time of surgery to death from any cause. |
Countries
United States
Contacts
CONTACTArnay Marshall
PRINCIPAL_INVESTIGATORZeynep Eroglu, MD
Moffitt Cancer Center
Outcome results
None listed