Description:
This phase II trial studies ipilimumab and nivolumab with immunoembolization in treating
participants with uveal melanoma that has spread to the liver. Monoclonal antibodies, such as
ipilimumab and nivolumab, 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 participants with uveal melanoma.
Title
- Brief Title: Ipilimumab and Nivolumab With Immunoembolization in Treating Participants With Metastatic Uveal Melanoma in the Liver
- Official Title: Ipilimumab and Nivolumab in Combination With Immunoembolization for the Treatment of Metastatic Uveal Melanoma
Clinical Trial IDs
- ORG STUDY ID:
18P.042
- NCT ID:
NCT03472586
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Ipilimumab | Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, 720801, 477202-00-9, 732442 | Treatment (ipilimumab, nivolumab, immunoembolization) |
Nivolumab | 946414-94-4, BMS-936558, ONO-4538, Opdivo | Treatment (ipilimumab, nivolumab, immunoembolization) |
Embolization Therapy | | Treatment (ipilimumab, nivolumab, immunoembolization) |
Purpose
This phase II trial studies ipilimumab and nivolumab with immunoembolization in treating
participants with uveal melanoma that has spread to the liver. Monoclonal antibodies, such as
ipilimumab and nivolumab, 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 participants 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (ipilimumab, nivolumab, immunoembolization) | Experimental | Participants receive ipilimumab IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Participants also undergo immunoembolization on day 2. Courses repeat every 3 weeks for 12 weeks in the absence of disease progression or unacceptable toxicity. Participants with complete response, partial response, or stable disease may receive nivolumab IV over 30 minutes on day 1 and undergo immunoembolization on day 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | - Ipilimumab
- Nivolumab
- Embolization Therapy
|
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 spiral
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 accepted and effective methods
of contraception and/or to abstain from sexual intercourse for at least 4 months (120
days) after the last dose of nivolumab and/or ipilimumab; sexually active males must
also use at least two accepted and effective methods of contraception and/or to
abstain from sexual intercourse for at least 4 months (120 days) after the last dose
of nivolumab and/or ipilimumab
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
- 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
- Occlusion of the main portal vein, or inadequate collateral flow around an occluded
portal vein as determined by angiography
- 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
- Significant arteriovenous shunt identified on angiography of the hepatic artery
- Positive for known human immunodeficiency virus (HIV) Infection
- Uncontrolled chronic obstructive pulmonary disease or previous known pulmonary
fibrosis
- Active infection
- Auto-immune disease including inflammatory bowel disease, lupus, rheumatoid arthritis,
but not including hypothyroidism or psoriasis if condition has been stable for 2
months or greater
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Hepatic metastasis stabilization rate by response criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) |
Time Frame: | At week 12 |
Safety Issue: | |
Description: | 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 Outcome Measures
Measure: | Incidence of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 |
Time Frame: | Up to 1 year |
Safety Issue: | |
Description: | Toxicity rates will be estimated with corresponding 95% confidence intervals. |
Measure: | Progression free survival (PFS) |
Time Frame: | From the start of the treatment to confirmation of progression of disease, assessed up to 1 year |
Safety Issue: | |
Description: | Will be estimated using the Kaplan-Meier method. |
Measure: | Overall survival |
Time Frame: | From the start of the treatment to confirmation of progression of disease, assessed up to 1 year |
Safety Issue: | |
Description: | Will be estimated using the Kaplan-Meier method. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Sidney Kimmel Cancer Center at Thomas Jefferson University |
Last Updated
May 28, 2020