Study of Adjuvant Ipilimumab and Nivolumab in Subjects With High-risk Ocular Melanoma

NCT03528408 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: HCRN-MEL17-309
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label, multi-site, single-arm Phase 2 study of adjuvant nivolumab combined with ipilimumab for the treatment of adult subjects with completely treated high-risk ocular melanoma, as defined in eligibility criteria, without evidence of metastatic disease. All patients enrolled to the study will be treated with nivolumab 240 mg IV every 2 weeks plus ipilimumab 1mg/kg IV every 6 weeks. 1 cycle = 6 weeks. Treatment will continue until disease progression, unacceptable toxicity, patient request to discontinue or completion of treatment. Subjects may receive up to 25 doses of nivolumab and 8 doses of ipilimumab

Conditions

Melanoma; Ocular Melanoma

Outcome Measures

Primary Outcomes (1)

• 3 year Relapse Free Survival (RFS)

  RFS is defined as time from registration to recurrence of disease or death from any cause.

  36 months

Secondary Outcomes (4)

• Median RFS

  12 months

• Overall Survival (OS)

  12 months

• 3 year OS

  36 months

• Assess Adverse Events

  36 months

Study Arms (1)

Nivolumab and Ipilimumab

EXPERIMENTAL

All patients enrolled to the study will be treated with nivolumab 240 mg IV every 2 weeks plus ipilimumab 1mg/kg IV every 6 weeks. 1 cycle = 6 weeks.

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Nivolumab 240 mg IV over 30 minutes given Day 1, 15 and 29 of each Cycle

Also known as: Opdivo

Nivolumab and Ipilimumab

Ipilimumab DRUG

Ipilimumab 1 mg/kg IV over 60 minutes given Day 1 of each Cycle

Also known as: Yervoy

Nivolumab and Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent. No dosing or adverse event data are currently available on the use of ipilimumab in combination with nivolumab in patients \< 18 years of age.
• 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
• year recurrent risk of more than 50% as defined by Impact Genetics, or
• Monosomy of chromosome 3 with apical tumor height \> 8mm (53).
• The primary tumor measured at least 12mm in largest basal diameter as clinically determined by the site investigator. Size is based on clinical assessment (e.g. by ultrasound or direct ophthalmoscopy) prior to enucleation or radiation therapy.
• Archival tumor tissue is required for subjects that have had enucleation; subjects that have had enucleation but do not have available archival tissue are not eligible for participation. Archival tissue is required if available for subjects that have not had enucleation; if not available these patients are still eligible.
• Patients must have undergone an adequate treatment for the primary ocular melanoma deemed appropriate by the treating physician.
• All participants must have been adequately treated for local disease and have documentation of distant/metastatic disease-free status by a complete physical examination and imaging studies within 4 weeks prior to registration. Imaging studies must include CT or 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 re-consented

You may not qualify if:

• 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 weeks 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
• Subjects that have undergone a solid organ or stem cell transplant.

Sponsors & Collaborators

• Suthee Rapisuwon: lead
• Bristol-Myers Squibb: collaborator

Study Sites (6)

University of California San Francisco

San Francisco, California, 94158, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Northwestern Univeristy Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University

New York, New York, 10032, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Melanoma; Uveal Melanoma

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Suthee Rapisuwon, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: May 7, 2018
• First Posted: May 17, 2018
• Study Start: July 26, 2018
• Primary Completion: May 1, 2023
• Study Completion: June 1, 2023
• Last Updated: April 11, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)