PRISM: Pre-Operative Radiotherapy and Immunotherapy for Sinonasal Melanoma

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed melanoma involving thenasal cavity and/or paranasal sinuses.

• Evidence of sinonasal tumor on clinical exam or imaging.

• No evidence of distant metastasis

• Patients must be evaluated by Head and Neck Surgery to establish surgical status asresectable, borderline resectable or unresectable.

• Patients must be planned for combination immunotherapy (e.g. ipilimumab andnivolumab or nivolumab and relatlimab).

• Patients must have a baseline skull base MRI unless contraindicated by medical orfinancial toxicity.

• ECOG performance status ≤3.

• Age ≥18 years because melanoma is extremely rare in patients <18 years of age and RTis considered high risk in this population due to risk of secondary malignancy andpotentially growing tissues that may be adversely impacted by RT.

• RT is a known teratogen. For this reason women of child-bearing potential and menmust agree to use adequate contraception (hormonal or barrier method of birthcontrol; abstinence) prior to study entry and for the duration of studyparticipation. (refer to MDA Policy CLN 1114) This includes all female patients,between the onset of menses and 55 years unless the patient presents with anapplicable exclusionary factor which may be one of the following: • Postmenopausal (no menses in greater than or equal to 12 consecutive months). • History ofhysterectomy or bilateral salpingo-oophorectomy. • Ovarian failure (FollicleStimulating Hormone and Estradiol in menopausal range, who have received WholePelvic Radiation Therapy). • History of bilateral tubal ligation or another surgicalsterilization procedure. Approved methods of birth control are as follows: Hormonalcontraception (i.e. birth control pills, injection, implant, transdermal patch,vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy,Subject/Partner post vasectomy, Implantable or injectable contraceptives, andcondoms plus spermicide. Not engaging in sexual activity for the total duration ofthe trial and the drug washout period is an acceptable practice; however periodicabstinence, the rhythm method, and the withdrawal method are not acceptable methodsof birth control. Should a woman become pregnant or suspect she is pregnant whileshe or her partner is participating in this study, she should inform her treatingphysician immediately.

• Men treated or enrolled on this protocol must also agree to use adequatecontraception prior to the study, for the duration of study participation, and 6months after completion of RT.

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with their ability to safely receive thestudy interventions are eligible for this trial.

• Ability to understand and the willingness to sign a written informed consentdocument.

Exclusion Criteria:

• Previous radiation therapy to the sinonasal area.

• Metastatic disease

• Pregnant women are excluded from this study because RT is a known teratogen.

• Patients who are less than 18 years of age because melanoma is extremely rare inthis population and the treatment agent is a known carcinogen.