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

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ClinicalTrials.gov Identifier: NCT04741997
Recruitment Status : Recruiting
First Posted : February 5, 2021
Last Update Posted : February 5, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

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.

Condition or disease Intervention/treatment Phase
Melanoma Stage III Melanoma Stage IV BRAF V600 Mutation Drug: Encorafenib Pill Drug: Binimetinib Pill Drug: Nivolumab Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Pilot Trial of Adjuvant Therapy Based on Pathologic Response After Neoadjuvant Encorafenib and Binimetinib in Advanced Melanoma
Actual Study Start Date : January 29, 2021
Estimated Primary Completion Date : January 2026
Estimated Study Completion Date : January 2027

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
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.
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

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.
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

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.
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

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.
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.




Primary Outcome Measures :
  1. Rate of Disease Relapse [ Time Frame: 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 Outcome Measures :
  1. Relapse Free Survival [ Time Frame: After surgery up to 24 weeks ]
    Relapse free survival is defined as time from surgery until disease relapse

  2. Rate of Pathologic Complete Response [ Time Frame: At 26 weeks ]
    Investigators will measure the rate of pathologic complete response after surgery.

  3. Rate of Non-Pathologic Complete Response [ Time Frame: At 26 weeks ]
    Investigators will measure the rate of non-pathologic complete response after surgery.

  4. Overall Response Rate [ Time Frame: 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).

  5. Overall Survival [ Time Frame: After surgery, up to 5 years ]
    Overall survival will be measured from time of surgery to death from any cause.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 an anti-PD-1/PD-L1 or CTLA-4 inhibitor or a 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 or anti-PD-1/PD-L1 therapy are not eligible. (Progression after stopping treatment is permitted.)
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04741997


Contacts
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Contact: Viola Voncken Brewster 813-745-1710 Viloa.VonckenBrewster@moffitt.org

Locations
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United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Viloa Voncken Brewster    813-745-1710    Viloa.VonckenBrewster@moffitt.org   
Principal Investigator: Zeynep Eroglu, MD         
Sub-Investigator: Andrew Brohl, MD         
Sub-Investigator: Nikhil Khushaslani, MD         
Sub-Investigator: Joseph Markowitz, MD, PhD         
Sub-Investigator: Ahmad Tarhini, MD, PhD         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Pfizer
Investigators
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Principal Investigator: Zeynep Eroglu, MD Moffitt Cancer Center
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT04741997    
Other Study ID Numbers: MCC-20641
First Posted: February 5, 2021    Key Record Dates
Last Update Posted: February 5, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Skin
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents