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

NCT04741997

Last updated date
Study Location
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Contact
813-745-1710

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Melanoma Stage III, Melanoma Stage IV, BRAF V600 Mutation
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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.

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Melanoma Stage III, Melanoma Stage IV, BRAF V600 MutationAdjuvant Therapy Based on Pathologic Response After Neoadjuvant Encorafenib Binimetinib in Melanoma
NCT04741997
  1. Tampa, Florida
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Adjuvant Therapy Based on Pathologic Response After Neoadjuvant Encorafenib Binimetinib in Melanoma
Official Title  ICMJE A Randomized Pilot Trial of Adjuvant Therapy Based on Pathologic Response After Neoadjuvant Encorafenib and Binimetinib in Advanced Melanoma
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Melanoma Stage III
  • Melanoma Stage IV
  • BRAF V600 Mutation
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Encorafenib Pill
    • Drug: Binimetinib Pill
  • 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.
    Interventions:
    • Drug: Encorafenib Pill
    • Drug: Binimetinib Pill
  • 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.
    Interventions:
    • Drug: Encorafenib Pill
    • Drug: Binimetinib Pill
  • 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
    • Drug: Binimetinib Pill
    • Drug: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 4, 2021)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2027
Estimated Primary Completion Date January 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 ?-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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Viola Voncken Brewster813-745-1710[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04741997
Other Study ID Numbers  ICMJE MCC-20641
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Zeynep Eroglu, MDMoffitt Cancer Center
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP