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

Study Purpose

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 Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04741997
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Early Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

H. Lee Moffitt Cancer Center and Research Institute
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Zeynep Eroglu, MD
Principal Investigator Affiliation Moffitt Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Melanoma Stage III, Melanoma Stage IV, BRAF V600 Mutation
Arms & Interventions

Arms

Active Comparator: Surveillance

Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have pathologic complete response they will receive adjuvant treatment for 24 weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery.

Experimental: Encorafenib and Binimetinib after Pathologic Complete Response

Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have pathologic complete response they will continue to receive encorafenib and binimetinib for 24 more weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery.

Experimental: Encorafenib and Binimetinib after Non-Pathologic Complete Response

Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have non-pathologic complete response they will continue to receive encorafenib and binimetinib for 24 more weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery.

Experimental: Nivolumab after Non-Pathologic Complete Response

Participants will receive 24 weeks of neoadjuvant encorafenib and binimetinib and then proceed to planned resection. If participants have non-pathologic complete response they will receive nivolumab for 24 weeks. Imaging will be conducted every 12 weeks for at least one year after surgery, and every 24 weeks for at least two years post-surgery.

Interventions

Drug: - Encorafenib Pill

Encorafenib 450 mg will be administered orally once per day in continuous 28-day cycles

Drug: - Binimetinib Pill

Binimetinib 45 mg will be administered orally twice per day in continuous 28-day cycles

Drug: - Nivolumab

Nivolumab will be administered at a dose of 480 mg IV infusion over 30 minutes every 4 weeks.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Moffitt Cancer Center, Tampa, Florida

Status

Recruiting

Address

Moffitt Cancer Center

Tampa, Florida, 33612

Site Contact

Viloa Voncken Brewster

Viloa.VonckenBrewster@moffitt.org

813-745-1710

The content provided by NBTS on clinical trials is for informational purposes only and is not a substitute for medical consultation with your healthcare provider. We do not recommend or endorse any specific study and you are advised to discuss the information shown with your healthcare provider. While we believe the information presented on this website to be accurate at the time of writing, we do not guarantee that its contents are correct, complete, or applicable to any particular individual situation. We strongly encourage individuals to seek out appropriate medical advice and treatment from their physicians. We cannot guarantee the availability of any clinical trial listed and will not be responsible if you are considered ineligible to participate in a given clinical trial. We are also not liable for any injury arising as a result of participation. For a full description of terms please refer to: Terms, Conditions & Privacy