Ipilimumab and Nivolumab in Combination With Immunoembolization for the Treatment of Metastatic Uveal Melanoma
Overview
- Phase
- Phase 2
- Intervention
- Ipilimumab
- Conditions
- Metastatic Malignant Neoplasm in the Liver
- Sponsor
- Sidney Kimmel Cancer Center at Thomas Jefferson University
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Hepatic Metastasis Stabilization Rate by Response Criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
- Status
- Completed
- Last Updated
- last year
Overview
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.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the clinical benefit of treatment with immunoembolization (IEMBO) in combination with ipilimumab and nivolumab. SECONDARY OBJECTIVES: I. Determine all treatment and immune related toxicities. II. Determine progression free survival. III. Determine overall survival.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •Failure to meet any of the criteria set forth in the inclusion criteria section
- •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
Arms & Interventions
Treatment (ipilimumab, nivolumab, immunoembolization)
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.
Intervention: Ipilimumab
Treatment (ipilimumab, nivolumab, immunoembolization)
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.
Intervention: Nivolumab
Treatment (ipilimumab, nivolumab, immunoembolization)
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.
Intervention: Embolization Therapy
Outcomes
Primary Outcomes
Hepatic Metastasis Stabilization Rate by Response Criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
Time Frame: At the end of 4th treatment cycle (Day 84 +/- 3 days). Cycles are 21 days.
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.
Secondary Outcomes
- Overall Survival(From the start of the treatment to confirmation of progression of disease, assessed up to 1 year)
- 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)