Pre-operative treatment for sinonasal melanoma using radiation and immunotherapy

Preoperative Radiotherapy and Immunotherapy for Sinonasal and Anorectal Mucosal Melanoma

This study is testing a new treatment plan that combines immunotherapy and radiation before surgery to see if it helps patients with sinonasal melanoma have better outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: ipilimumab, nivolumab, relatlimab, immunotherapy, Radiation
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT05546827 on ClinicalTrials.gov

What this trial studies

This clinical research focuses on patients with non-metastatic sinonasal melanoma who will receive a combination of immunotherapy followed by radiation therapy before surgical resection. The study aims to evaluate the effectiveness of this neoadjuvant treatment approach by measuring the rate of pathologic response, defined as less than 50% viable tumor or more than 50% fibrosis in the tumor tissue. Patients will undergo imaging and clinical evaluations to confirm their eligibility and surgical status. The goal is to improve surgical outcomes and overall prognosis for these patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed sinonasal melanoma that is resectable and without distant metastasis.

Not a fit: Patients with metastatic sinonasal melanoma or those who are not candidates for surgical resection may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved surgical outcomes and survival rates for patients with sinonasal melanoma.

How similar studies have performed: While the specific combination of pre-operative radiation and immunotherapy for sinonasal melanoma is novel, similar approaches in other cancers have shown promising results.

Eligibility criteria

Inclusion Criteria

For all patients

* Evidence of mucosal tumor on clinical exam or imaging.
* No evidence of distant metastasis
* Patients must be planned for combination immunotherapy (e.g. ipilimumab and nivolumab or nivolumab and relatlimab).
* ECOG performance status ≤3.
* Age ≥18 years because melanoma is extremely rare in patients \<18 years of age and RT is considered high risk in this population due to risk of secondary malignancy and potentially growing tissues that may be adversely impacted by RT.
* RT is a known teratogen. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (refer to MDA Policy CLN 1114) This includes all female patients, between the onset of menses and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
* Postmenopausal (no menses in greater than or equal to 12 consecutive months).
* History of hysterectomy or bilateral salpingo-oophorectomy.
* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
* History of bilateral tubal ligation or another surgical sterilization procedure. Approved methods of birth control are as follows: Hormonal contraception (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, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should 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 study participation, and 6 months after completion of RT.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with their ability to safely receive the study interventions are eligible for this trial.
* Ability to understand and the willingness to sign a written informed consent document.

For Arm 1 patients (sinonasal melanoma)

* Patients must have histologically or cytologically confirmed melanoma involving the nasal cavity and/or paranasal sinuses.
* Patients must be evaluated by Head and Neck Surgery to establish surgical status as resectable, borderline resectable or unresectable.
* Patients must have a baseline skull base MRI unless contraindicated by medical or financial toxicity.

For Arm 2 patients (anorectal melanoma)

* Patients must have histologically or cytologically confirmed melanoma involving the anorectal canal.
* Patients must be evaluated by the surgical team to establish primary tumor surgical status as: (1) resectable with sphincter sparing approach, (2) resectable with abdominoperineal resection, or (3) unresectable/requiring surgery greater than abdominoperineal resection.
* Patients must have a baseline rectal MRI unless contraindicated by medical or financial toxicity.

2.2 Exclusion Criteria

* Previous radiation therapy to the planned target area (sinonasal for Arm 1 and anorectal for Arm 2).
* 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 in this population and the treatment agent is a known carcinogen.

Where this trial is running

Houston, Texas

• M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Devarati Mitra, MD

Conditions Sinonasal Melanoma; Anorectal Melanoma