Pembrolizumab and Hypofractionated Radiation Therapy for the Treatment of Mucosal Melanoma

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

This is an open-label, single center, one cohort, non-randomized, phase 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

• Status: Recruiting
• Conditions: Mucosal Melanoma of the Head and Neck
• Intervention / Treatment: Drug: Pembrolizumab; Radiation: Hypofractionated radiation therapy

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: George Ansstas, M.D.; Phone Number: 314-362-5677; Email: gansstas@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Ningying Wu, Ph.D.
      • Contact: George Ansstas, M.D.; Phone Number: 314-362-5677; Email: gansstas@wustl.edu
      • Principal Investigator: George Ansstas, M.D.
      • Sub-Investigator: Matt Spraker, M.D., Ph.D.

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

1

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.

Drug: Pembrolizumab; Pembrolizumab is commercially available; Other Names: Keytruda; Radiation: Hypofractionated radiation therapy; 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	Measure Description	Time Frame
Local tumor control rate	Tumor control rate is defined as the percentage of subjects at 12 months who are free of local recurrence, regional recurrence, distant recurrence, second primary cancer, or death.	1 year after completion of treatment (estimated to be 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival (RFS)	-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.	At 3 years after completion of treatment (estimated to be 4 years)
Distant metastasis-free survival	-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.	At 3 years after completion of treatment (estimated to be 4 years)
Overall survival	-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.	At 3 years after completion of treatment (estimated to be 4 years)
Number of treatment-related grade 3 or greater adverse events	The total number of adverse events determined to be treatment related and grade 3 or higher as assessed using CTCAE v5.0 criteria.	Baseline through 90 days after end of treatment (estimated to be 15 months)
Number of treatment discontinuations due to treatment-related adverse events	The total number of participants who discontinued treatment due to treatment-related adverse events as assessed using CTCAE v5.0 criteria.	Through end of treatment (estimated to be 1 year)

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2020
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2032

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 (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: 202003124

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