Pembrolizumab and Hypofractionated Radiation Therapy for the Treatment of Mucosal Melanoma

Mucosal Melanoma of the Head and Neck Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04318717
• Other study ID #: 202003124
• Status: Recruiting
• Phase: Phase 2
• Start date: May 29, 2020
• Est. completion date: July 31, 2030

Study information

• Verified date: November 2023
• Source: Washington University School of Medicine
• Contact: George Ansstas, M.D.
• Phone: 314-362-5677
• Email: gansstas[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: July 31, 2030
• Est. primary completion date: July 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma
• Mucosal Melanoma of the Head and Neck

Intervention

Drug:
• Pembrolizumab
Pembrolizumab is commercially available

Radiation:
• Hypofractionated radiation therapy
It is preferred to leave at least 48 hours between fractions. Daily imaging to verify accurate set-up is mandatory.

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local tumor control rate		1 year
Secondary	Number of treatment-related grade 3 or greater adverse events		Baseline through 30 days after end of treatment (estimated to be 13 months)
Secondary	Number of treatment discontinuations due to treatment-related adverse events		Through end of treatment (estimated to be 12 months)
Secondary	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.	Through completion of follow-up (estimated to be 48 months)
Secondary	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.	Through completion of follow-up (estimated to be 48 months)
Secondary	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.	Through completion of follow-up (estimated to be 48 months)

External Links

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