Pembrolizumab and Hypofractionated Radiation Therapy for the Treatment of Mucosal Melanoma

November 21, 2023 updated by: Washington University School of Medicine

Adjuvant Pembrolizumab and Hypofractionated Radiation Therapy for the Treatment of Mucosal Melanoma

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.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • George Ansstas, M.D.
        • Sub-Investigator:
          • Matt Spraker, M.D., Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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/Interstitial lung disease that required maintenance steroids (>10 mg of prednisone) or current pneumonitis/interstitial lung disease.
  • Has received a live vaccine or live-attenuated vaccination within 30 days of planned treatment start. Administration of killed vaccines is allowed.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab + Hypofractionated radiation therapy
  • Pembrolizumab 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 90 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 is commercially available
Other Names:
  • Keytruda
It is preferred to leave at least 48 hours between fractions. Daily imaging to verify accurate set-up is mandatory.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Local tumor control rate
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Baseline through 30 days after end of treatment (estimated to be 13 months)
Number of treatment discontinuations due to treatment-related adverse events
Time Frame: Through end of treatment (estimated to be 12 months)
Through end of treatment (estimated to be 12 months)
Relapse-free survival (RFS)
Time Frame: Through completion of follow-up (estimated to be 48 months)
-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.
Through completion of follow-up (estimated to be 48 months)
Distant metastasis-free survival
Time Frame: Through completion of follow-up (estimated to be 48 months)
-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.
Through completion of follow-up (estimated to be 48 months)
Overall survival
Time Frame: Through completion of follow-up (estimated to be 48 months)
-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.
Through completion of follow-up (estimated to be 48 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: George Ansstas, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 29, 2020

Primary Completion (Estimated)

July 31, 2027

Study Completion (Estimated)

July 31, 2030

Study Registration Dates

First Submitted

March 20, 2020

First Submitted That Met QC Criteria

March 20, 2020

First Posted (Actual)

March 24, 2020

Study Record Updates

Last Update Posted (Estimated)

November 22, 2023

Last Update Submitted That Met QC Criteria

November 21, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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