Adjuvant Therapy Based on Pathologic Response After Neoadjuvant Encorafenib Binimetinib in Melanoma

Launched by H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE · Feb 4, 2021

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with melanoma that has a specific genetic mutation called BRAFV600. The goal is to see how well patients respond to a combination of drugs called encorafenib and binimetinib after they have undergone initial treatment. Researchers want to find out if the patients who achieve a complete response (meaning there are no signs of cancer) or those who do not have a complete response have different chances of the disease coming back after additional treatment.

To participate in this trial, individuals must be at least 18 years old and have a confirmed diagnosis of melanoma with the BRAFV600 mutation. They should be in good general health, meaning they can perform daily activities without much trouble. Participants will receive close monitoring and care throughout the study. It's important to know that there are specific medications and foods that need to be avoided during the trial, and certain health conditions may disqualify someone from participating. If you or a loved one are interested, talking to a healthcare provider can help determine if this trial is a good fit.

Gender

ALL

Eligibility criteria

• 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.