Clinical Trials /

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

NCT03472586

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.

Related Conditions:
  • Uveal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

  • Eye and Orbit

Interventions

DrugSynonymsArms
IpilimumabAnti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, 720801, 477202-00-9, 732442Treatment (ipilimumab, nivolumab, immunoembolization)
Nivolumab946414-94-4, BMS-936558, ONO-4538, OpdivoTreatment (ipilimumab, nivolumab, immunoembolization)
Embolization TherapyTreatment (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

NameTypeDescriptionInterventions
Treatment (ipilimumab, nivolumab, immunoembolization)ExperimentalParticipants 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

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