Combined Immunotherapy with Ipilimumab and Nivolumab or Nivolumab and Relatlimab and Radiation Therapy before Surgery for the Treatment of Sinonasal and Anorectal Melanoma
This phase II trial tests combined immunotherapy of ipilimumab and nivolumab or nivolumab and relatlimab and radiation therapy before surgery in patients with sinonasal and anorectal melanoma. Immunotherapy with ipilimumab and nivolumab or nivolumab and relatlimab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving immunotherapy and undergoing radiation therapy before surgery may make the tumor smaller and may reduce the amount of normal tissue that needs to be removed. Patients who are able to have the entire tumor removed without residual disease left behind may do better than those who have disease remaining after surgery.
Inclusion Criteria
- 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)
- Eastern Cooperative Oncology Group (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 MD Anderson [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
- ARM I PATIENTS (SINONASAL MELANOMA): Patients must have histologically or cytologically confirmed melanoma involving the nasal cavity and/or paranasal sinuses
- ARM I PATIENTS (SINONASAL MELANOMA): Patients must be evaluated by head and neck surgery to establish surgical status as resectable, borderline resectable or unresectable
- ARM I PATIENTS (SINONASAL MELANOMA): Patients must have a baseline skull base MRI unless contraindicated by medical or financial toxicity
- ARM II PATIENTS (ANORECTAL MELANOMA): Patients must have histologically or cytologically confirmed melanoma involving the anorectal canal
- ARM II PATIENTS (ANORECTAL MELANOMA): 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
- ARM II PATIENTS (ANORECTAL MELANOMA): Patients must have a baseline rectal MRI unless contraindicated by medical or financial toxicity
Exclusion Criteria
- Previous radiation therapy to the sinonasal 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
Additional locations may be listed on ClinicalTrials.gov for NCT05546827.
Locations matching your search criteria
United States
Texas
Houston
PRIMARY OBJECTIVES:
I. To determine the rate of pathologic response (<= 50% viable tumor or > 50% fibrosis) for non-metastatic sinonasal mucosal melanoma (sinonasal melanoma) patients having surgical resection after receiving neoadjuvant combination immunotherapy followed by radiation therapy.
II. To determine the rate of pathologic response (<50% viable tumor or >50% fibrosis) for non-metastatic anorectal melanoma patients receiving neoadjuvant intent combination immunotherapy followed by radiation therapy.
SECONDARY OBJECTIVES:
I. To determine the rate of surgical resection.
II. To determine the rate of negative margin surgical resection.
III. To determine the rate of complete pathologic response (CR) and near complete pathologic response (nCR).
IV. To determine the Response Evaluation Criteria in Solid Tumors (RECIST) objective radiologic response rate.
V. To determine the rate of in-field radiation therapy (RT)-associated acute toxicity.
VI. To determine the rate of in-field surgical toxicity.
VII. To determine the rate of in-field late toxicity.
VIII. To determine the time to local recurrence.
IX. To determine the time to non-nodal locoregional recurrence.
X. To determine the time to nodal recurrence.
XI. To determine the time to distant metastasis.
XII. To determine progression-free survival.
XIII. To determine disease-specific survival.
XIV. To assess changes in patient quality of life in response to therapy.
EXPLORATORY OBJECTIVES:
I. To explore tissue and blood-based biomarkers of response therapy in patients co-consented to protocol PA18-0644.
II. To measure changes in advanced magnetic resonance imaging (MRI) parameters in response to therapy and correlate to pathologic response.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Patients with sinonasal melanoma receive combined immunotherapy of ipilimumab and nivolumab or nivolumab and relatlimab for 1-6 cycles and then undergo neoadjuvant RT over 20 fractions once daily (QD) over 4 weeks in the absence of disease progression or unacceptable toxicity, followed by surgery on study. Patients undergo a nasopharyngoscopy during screening and follow-up. Patients undergo MRI, computed tomography (CT), and/or positron emission tomography (PET) scan throughout the trial. Patients undergo a biopsy during screening and on study. Patients may also undergo blood sample collection throughout the trial.
ARM II: Patients with anorectal melanoma receive combined immunotherapy of ipilimumab and nivolumab or nivolumab and relatlimab for 1-6 cycles or as clinically indicated and then undergo neoadjuvant RT over 5 fractions QD over 1 week or 15 fractions QD over 3 weeks in the absence of disease progression or unacceptable toxicity on study. Patients who show complete response to treatment undergo biopsy or transanal excision (TAE) on study. Patients also undergo MRI, CT, and/or PET scan throughout the trial. Additionally, patients undergo a biopsy during screening and on study. Patients may also undergo blood sample collection throughout the trial, and may undergo surgery, proctoscopy and/or sigmoidoscopy on the trial.
After completion of study treatment, patients are followed up at months 3, 6, 12, 18, and 24.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorDevarati Mitra
- Primary ID2022-0330
- Secondary IDsNCI-2022-07760
- ClinicalTrials.gov IDNCT05546827