Clinical Trials /

Pembrolizumab and Hypofractionated Radiation Therapy for the Treatment of Mucosal Melanoma

NCT04318717

Description:

This is an open-label, single center, one cohort, non-randomized, phase I/II study. The aim is to evaluate the efficacy and safety of the combination of hypofractionated radiotherapy (HRT) and pembrolizumab on local tumor control in mucosal melanoma patients. Treatment effect will be compared with historical radiation therapy-alone control data.

Related Conditions:
  • Mucosal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and Hypofractionated Radiation Therapy for the Treatment of Mucosal Melanoma
  • Official Title: Adjuvant Pembrolizumab and Hypofractionated Radiation Therapy for the Treatment of Mucosal Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 202003124
  • NCT ID: NCT04318717

Conditions

  • Mucosal Melanoma of the Head and Neck

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaPembrolizumab + Hypofractionated radiation therapy

Purpose

This is an open-label, single center, one cohort, non-randomized, phase I/II study. The aim is to evaluate the efficacy and safety of the combination of hypofractionated radiotherapy (HRT) and pembrolizumab on local tumor control in mucosal melanoma patients. Treatment effect will be compared with historical radiation therapy-alone control data.

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + Hypofractionated radiation therapyExperimentalPembrolizumab will be given intravenously over 30 minutes (-5/+10 minutes) at a dose of 200 mg on an outpatient basis on Day 1 of each 21-day cycle for a total of up to 12 months (17 cycles). Hypofractionated radiation therapy may be given at any point during the first 2 cycles of pembrolizuimab. It should begin within 60 days of surgical resection. Intensity modulated radiation therapy (IMRT) or intensity modulated proton therapy (IMPT) are to be used exclusively. IMRT or IMPT will be delivered twice per week in five fractions of 6 Gy given over 2.5 weeks totaling 30 Gy.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed mucosal melanoma that has undergone surgical
             resection. Patient must not have received prior radiation therapy within the area of
             interest.

          -  At least 16 years of age.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 70%)

          -  Normal bone marrow and organ function as defined below:

               -  Absolute neutrophil count ≥ 1,200/mcL

               -  Platelets ≥ 100,000/mcL

               -  Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)

               -  AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

               -  Creatinine clearance > 30 mL/min by Cockcroft-Gault

          -  The effects of pembrolizumab on the developing human fetus are unknown. For this
             reason, women of childbearing potential and men must agree to use adequate
             contraception (hormonal or barrier method of birth control, abstinence) prior to study
             entry, for the duration of study participation, and 6 months after last dose of
             pembrolizumab. Should a woman become pregnant or suspect she is pregnant while
             participating in this study, she must inform her treating physician immediately. Men
             treated or enrolled on this protocol must also agree to use adequate contraception
             prior to the study, for the duration of the study, and 6 months after last dose of
             pembrolizumab.

          -  Ability to understand and willingness to sign an IRB approved written informed consent
             document (or that of legally authorized representative, if applicable).

        Exclusion Criteria:

          -  A history of other malignancy with the exception of malignancies for which all
             treatment was completed at least 2 years before registration and the patient has no
             evidence of disease.

          -  Received radiation therapy within the area of interest.

          -  Currently receiving any other investigational agents.

          -  Metastatic disease.

          -  A history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to pembrolizumab or other agents used in the study.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
             arrhythmia.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of study
             treatment. The use of up to 10 mg/day of prednisone or equivalent is approved and does
             not exclude the patient from the trial.

          -  Active autoimmune disease that has required systemic treatment in past 2 years (i.e.,
             with use of disease modifying agents, > 10 mg of prednisone per day, or
             immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
             physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
             etc.) is not considered a form of systemic treatment. The use of up to 10 mg/day of
             prednisone or equivalent is approved and does not exclude the patient from the trial.

          -  Has a history of (non-infectious) pneumonitis that required maintenance steroids (>10
             mg of prednisone) or current pneumonitis.

          -  Has received a live-virus vaccination within 30 days of planned treatment start.
             Seasonal flu vaccines that do not contain live virus are permitted.

          -  Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
             pregnancy test within 14 days of study entry.

          -  Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or
             they have a history of AIDS-defining opportunistic infection within the 12 months
             prior to registration. Concurrent treatment with effective ART according to DHHS
             treatment guidelines is recommended.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Local tumor control rate
Time Frame:1 year
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of treatment-related grade 3 or greater adverse events
Time Frame:Baseline through 30 days after end of treatment (estimated to be 13 months)
Safety Issue:
Description:
Measure:Number of treatment discontinuations due to treatment-related adverse events
Time Frame:Through end of treatment (estimated to be 12 months)
Safety Issue:
Description:
Measure:Relapse-free survival (RFS)
Time Frame:3 years
Safety Issue:
Description:-defined as the duration of time from the start date of study treatment to the date of earliest disease relapse or death, whichever occurs first. Patients who neither relapse nor die by the data cutoff date will be censored at the last follow up date.
Measure:Distant metastasis-free survival
Time Frame:3 years
Safety Issue:
Description:-defined as the duration of time from the start date of study treatment to the date of appearance of a distant metastasis or death, whichever occurs first. Patients who neither develop distant metastasis nor die by the data cutoff date will be censored at the last follow up date.
Measure:Overall survival
Time Frame:3 years
Safety Issue:
Description:-defined as the duration of time from the start date of study treatment to death from any cause. Patients who are alive by the data cutoff date will be censored at the last follow up date.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

March 20, 2020