Adjuvant therapy for melanoma based on treatment response

A Randomized Pilot Trial of Adjuvant Therapy Based on Pathologic Response After Neoadjuvant Encorafenib and Binimetinib in Advanced Melanoma

This study tests if a combination of new medications can help people with melanoma who have a specific gene mutation stay cancer-free after their initial treatment.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Academic / other)
• Drugs / interventions: binimetinib, radiation
• Locations: 1 site (Tampa, Florida)
• Trial ID: NCT04741997 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of adjuvant therapy following neoadjuvant treatment in patients with melanoma who have a BRAF V600 mutation. It focuses on assessing disease relapse rates based on whether patients achieve a pathologic complete response or not after initial therapy. The intervention includes the use of Encorafenib, Binimetinib, and Nivolumab. The goal is to determine the optimal postoperative treatment strategy to reduce the risk of disease recurrence.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed melanoma and a BRAF V600 mutation, either stage III or IV.

Not a fit: Patients without a BRAF V600 mutation or those with other types of melanoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the risk of melanoma relapse in patients with specific genetic mutations.

How similar studies have performed: Other studies have shown promising results with targeted therapies in melanoma, indicating potential for success with this approach.

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.

Where this trial is running

Tampa, Florida

• Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Zeynep Eroglu, MD — Moffitt Cancer Center
• Study coordinator: Arnay Marshall

Conditions Melanoma Stage III; Melanoma Stage IV; BRAF V600 Mutation; Skin