Ipilimumab and Nivolumab in Treating Patients with High-Risk Ocular Melanoma
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 28 days prior to registration
- Patients must have clinically confirmed ocular melanoma diagnosed by a retinal specialist or ocular oncologist. NOTE: Patients with cutaneous melanoma, acral melanoma, mucosal melanoma, or conjunctival melanoma are ineligible
- Patients must have ocular melanoma that is considered high-risk for recurrence as defined by one of the following criteria: * Gene expression profile using 15-gene panel (Castle Bioscience) and be classified as class 2, or * 3-year recurrent risk of more than 50% as defined by Impact Genetics, or * Monosomy of chromosome 3 with apical tumor height > 8 mm
- Patients must have undergone an adequate treatment for the primary ocular melanoma deemed appropriate by the treating physician
- All disease must be treated with no clinical, or radiologic evidence of residual ocular melanoma. All participants must have disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to registration. Imaging studies must include computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis. Brain MRI should be performed only as clinically indicated
- Patients must be registered within 180 days of the last treatment performed to render the patient free of disease
- Patient may have received prior radiation therapy to the primary site, including after the surgical resection. No systemic radiation for metastatic ocular melanoma is permitted
- Subject re-enrollment: This study permits the re-enrollment of a participant who has discontinued the study as a screen failure. If re-enrolled, the participant must be reconsented
- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (obtained within 28 days prior to registration)
- Platelets >= 100,000 cells/mm^3 (obtained within 28 days prior to registration)
- Hemoglobin (Hgb) >= 9 g/dL (NOTE: The use of transfusion or to achieve Hgb >= 10 g/dl is acceptable) (obtained within 28 days prior to registration)
- Serum creatinine =< 1.5 x institutional upper limit normal (IULN) OR estimated glomerular filtration rate (eGFR) > 30mL/min for participant with creatinine levels > 1.5 x ULN (obtained within 28 days prior to registration)
- Bilirubin =< 1.5 x institutional upper limit of normal (IULN) (except subjects with Gilbert syndrome who can have total bilirubin >= 3.0 mg/dL) (obtained within 28 days prior to registration)
- Aspartate aminotransferase (AST) =< 3.0 x IULN (obtained within 28 days prior to registration)
- Alanine aminotransferase (ALT) =< 3.0 x IULN (obtained within 28 days prior to registration)
- Alkaline phosphatase =< 2.5 IULN (obtained within 28 days prior to registration)
- Neuropathy (sensory and motor) grade =< 1 (Common Terminology Criteria for Adverse Events [CTCAE] version [v]4)
- Females of childbearing potential must have a negative serum pregnancy test at screening and within 24 hours prior to initiation of study treatment. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
- Females of childbearing potential and non-vasectomized males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 5 months after last dose of study drug (females) and 7 months after last dose of study drug for (males). The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
- Patients with evidence of distant metastases (stage IV ocular melanoma) are not eligible
- Patients with local or orbital recurrence are not eligible
- Patients with cutaneous, mucosal, acral or conjunctival melanoma are not eligible
- Subjects with active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment or conditions not expected to recur in the absences of an external trigger are permitted to enroll
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 years of study drug administration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- Participants with previous malignancies are excluded unless a complete remission was achieved at 12 months prior to study entry and no additional therapy is required or anticipated to be required during the study period (exceptions include but are not limited to, non-melanoma skin cancers; in situ bladder cancer, in situ gastric cancer, or in situ colon cancer; in situ cervical cancer/dysplasia; or breast carcinoma in situ)
- History of grade >= 3 allergy to human monoclonal antibodies
- Subjects who have had prior immunotherapy, including but not limited to interferon alfa-2b, PEG-IFN, anti-PD-1, anti-PD-L1, anti-CTLA4 intra-tumoral or vaccine therapies are not permitted to enroll
- Psychological, familial, sociological, or geographical conditions that potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the participant before registration in the trial
- Subjects who are receiving any other investigational agents
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring systemic therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Note: Testing for HIV must be performed at sites where mandated locally
- Subjects who are unable or unwilling to discontinue use of prohibited medications
- Subject is a prisoner
District of Columbia
I. Compare relapse-free survival (RFS) rate at 3 years of patients with locally treated high-risk ocular melanoma treated with adjuvant nivolumab/ipilimumab combination versus a matched contemporaneous control population from the Cure OM Registry.
I. Compare median RFS in resected high-risk ocular melanoma in treatment arm versus a matched historical control population.
II. Compare median overall survival (OS) and 3–year OS rate in resected high-risk ocular melanoma in treatment arm versus contemporaneous control population.
III. Assess the overall safety and tolerability of the combination regimen in patients with resected high-risk ocular melanoma.
I. Collect baseline and serial blood and stool samples from each participant and store for future circulating biomarker research to identify potential predictors of response and toxicities to the treatment.
Patients receive nivolumab intravenously (IV) over 30 minutes on days 1, 14, and 28, and ipilimumab IV over 60 minutes on day 1. Treatment repeats every 6 weeks for up to 1 year (25 doses of nivolumab and 8 doses of ipilimumab) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for 5 years.
Trial Phase Phase II
Trial Type Treatment
MedStar Georgetown University Hospital
- Primary ID 2018-0319
- Secondary IDs NCI-2018-02700
- Clinicaltrials.gov ID NCT03528408