Ipilimumab and Nivolumab With Immunoembolization in Treating Participants With Metastatic Uveal Melanoma in the Liver

NCT03472586 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 18P.042JT 10364
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies ipilimumab and nivolumab with immunoembolization in treating patients with uveal melanoma that has spread to the liver. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Immunoembolization may kill tumor cells due to loss of blood supply and develop an immune response against tumor cells. Giving ipilimumab and nivolumab with immunoembolization may work better in treating patients with uveal melanoma.

Conditions

Metastatic Malignant Neoplasm in the Liver; Metastatic Uveal Melanoma; Stage IV Uveal Melanoma AJCC v7

Outcome Measures

Primary Outcomes (1)

• Hepatic Metastasis Stabilization Rate by Response Criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)

  Defined as complete response + partial response + stable disease. Rated by Response Evaluation Criteria in Solid Tumors version 1.1. The estimate of the hepatic metastasis stabilization rate will be presented with corresponding 95% confidence intervals. The method of Atkinson and Brown will be used to adjust for the two-stage design.

  At the end of 4th treatment cycle (Day 84 +/- 3 days). Cycles are 21 days.

Secondary Outcomes (3)

• Incidence of Adverse Events

  Up to 1 year

• Progression Free Survival (PFS)

  From the start of the treatment to confirmation of progression of disease, assessed up to 1 year

• Overall Survival

  From the start of the treatment to confirmation of progression of disease, assessed up to 1 year

Study Arms (1)

Treatment (ipilimumab, nivolumab, immunoembolization)

EXPERIMENTAL

Patients receive ipilimumab IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Patients also undergo immunoembolization on day 2. Cycles repeat every 3 weeks for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with complete response, partial response, or stable disease may receive nivolumab IV on day 1 and undergo immunoembolization on day 2. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. The interval between treatments may be extended up to every 6 weeks at the discretion of the treating physician.

Biological: Ipilimumab; Biological: Nivolumab; Drug: Embolization Therapy

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, 720801, 477202-00-9, 732442

Treatment (ipilimumab, nivolumab, immunoembolization)

Nivolumab BIOLOGICAL

Given IV

Also known as: 946414-94-4, BMS-936558, ONO-4538, Opdivo

Treatment (ipilimumab, nivolumab, immunoembolization)

Embolization Therapy DRUG

Undergo immunoembolization

Treatment (ipilimumab, nivolumab, immunoembolization)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic uveal melanoma in the liver; patients must have at least one measurable liver metastasis that is \>= 10 mm in longest diameter by computed tomography (CT) scan or magnetic resonance imaging (MRI)
• The total volume of the tumors must be less than 50% of the liver volume
• Willingness and ability to give informed consent
• Agreement to access archival tissue or agreement for tumor biopsy prior to treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1
• Serum creatinine =\< 2.0 mg/dl
• Granulocyte count \>= 1000/mm\^3
• Platelet count \>= 100,000/mm\^3
• Bilirubin =\< 2.0 mg/ml
• Albumin \>= 3.0 g/dl
• Prothrombin time (PT)/partial thromboplastin time (PTT) less than 1.5 times normal
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 x upper limit of normal (ULN)
• Alkaline phosphatase less than 1.5 times ULN (grade 1)
• Women must not be pregnant or breast-feeding
• Women of child-bearing potential must use at least two other accepted and effective methods of contraception and/or to abstain from sexual intercourse for at least 23 weeks after the last dose of nivolumab and/or ipilimumab and sexually active males must use at least two other accepted and effective methods of contraception and/or to abstain from sexual intercourse for at least 31 weeks after the last dose of nivolumab and/or ipilimumab

You may not qualify if:

• Previous systemic exposure to anti-CTLA-4 antibody or anti-PD1 antibody
• Previous liver-directed treatments including chemoembolization, radiosphere, hepatic arterial perfusion, or drug-eluting beads; liver resection and focal ablation are permitted
• Presence of symptomatic liver failure including ascites and hepatic encephalopathy
• Presence of untreated brain metastases; if patients have had previous treatment for the brain metastasis, an MRI or CT scan of the brain must confirm the stabilization of the brain metastasis for more than 2 months
• Presence of uncontrolled hypertension or congestive heart failure, or acute myocardial infarction within 6 months of entry
• Presence of any other medical complication that implies survival of less than six months
• Uncontrolled severe bleeding tendency or active gastrointestinal (GI) bleeding
• Significant allergic reaction to contrast dye or granulocyte-macrophage colony-stimulating (GM-CSF)
• Immunosuppressive treatments within 4 weeks prior to embolization, unless prednisone =\< 5 mg or equivalent
• Pregnancy or breast-feeding women
• Patients with active hepatitis with serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) equal or greater than 5 times normal
• Biliary obstruction, biliary stent or prior biliary surgery except cholecystectomy
• Positive for known human immunodeficiency virus (HIV) Infection
• Uncontrolled chronic obstructive pulmonary disease or previous known pulmonary fibrosis
• Active infection

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Sidney Kimmel Cancer Center at Thomas Jefferson University
• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab; Embolization, Therapeutic

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; 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; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Hemostatic Techniques; Therapeutics; Therapeutic Occlusion

Results Point of Contact

• Title: Marlana Orloff, MD
• Organization: Thomas Jefferson University

marlana.orloff@jefferson.edu

215-955-9974

Study Officials

• Marlana Orloff, MD

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 21, 2018
• Study Start: May 2, 2018
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2024
• Last Updated: April 24, 2025
• Results First Posted: November 29, 2023

Record last verified: 2025-04

Locations

US (1)