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

Melanoma Stage IV Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04741997
• Other study ID #: MCC-20641
• Status: Recruiting
• Phase: Early Phase 1
• Start date: May 24, 2021
• Est. completion date: January 2027

Study information

• Verified date: February 2024
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: Krystal Victoria
• Phone: 813-745-0218
• Email: Krystal.Victoria[@]moffitt.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 2027
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• BRAF V600 Mutation
• Melanoma
• Melanoma Stage III
• Melanoma Stage IV

Intervention

Drug:
• Encorafenib Pill
Encorafenib 450 mg will be administered orally once per day in continuous 28-day cycles
• Binimetinib Pill
Binimetinib 45 mg will be administered orally twice per day in continuous 28-day cycles
• Nivolumab
Nivolumab will be administered at a dose of 480 mg IV infusion over 30 minutes every 4 weeks.

Locations

Country	Name	City	State
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Disease Relapse	Investigators will estimate the rate of disease relapse after neoadjuvant therapy based on pathologic complete response status and postoperative adjuvant therapy within each arm.	After surgery up to 24 weeks
Secondary	Relapse Free Survival	Relapse free survival is defined as time from surgery until disease relapse	After surgery up to 24 weeks
Secondary	Rate of Pathologic Complete Response	Investigators will measure the rate of pathologic complete response after surgery.	At 26 weeks
Secondary	Rate of Non-Pathologic Complete Response	Investigators will measure the rate of non-pathologic complete response after surgery.	At 26 weeks
Secondary	Overall Response Rate	Overall response rate will be measured after neoadjuvant therapy (for participants who have measurable disease per RECIST 1.1 at start of neoadjuvant therapy).	Up to 26 weeks
Secondary	Overall Survival	Overall survival will be measured from time of surgery to death from any cause.	After surgery, up to 5 years