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

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ClinicalTrials.gov Identifier: NCT03472586
Recruitment Status : Recruiting
First Posted : March 21, 2018
Last Update Posted : May 28, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Tracking Information
First Submitted Date  ICMJE March 14, 2018
First Posted Date  ICMJE March 21, 2018
Last Update Posted Date May 28, 2020
Actual Study Start Date  ICMJE May 2, 2018
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2018)
Hepatic metastasis stabilization rate by response criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) [ Time Frame: At week 12 ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2018)
  • Incidence of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: Up to 1 year ]
    Toxicity rates will be estimated with corresponding 95% confidence intervals.
  • Progression free survival (PFS) [ Time Frame: From the start of the treatment to confirmation of progression of disease, assessed up to 1 year ]
    Will be estimated using the Kaplan-Meier method.
  • Overall survival [ Time Frame: From the start of the treatment to confirmation of progression of disease, assessed up to 1 year ]
    Will be estimated using the Kaplan-Meier method.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ipilimumab and Nivolumab With Immunoembolization in Treating Participants With Metastatic Uveal Melanoma in the Liver
Official Title  ICMJE Ipilimumab and Nivolumab in Combination With Immunoembolization for the Treatment of Metastatic Uveal Melanoma
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Eye and Orbit
Intervention  ICMJE
  • Biological: Ipilimumab
    Given IV
    Other Names:
    • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
    • BMS-734016
    • MDX-010
    • 720801
    • 477202-00-9
    • 732442
  • Biological: Nivolumab
    Given IV
    Other Names:
    • 946414-94-4
    • BMS-936558
    • ONO-4538
    • Opdivo
  • Drug: Embolization Therapy
    Undergo immunoembolization
Study Arms  ICMJE Experimental: Treatment (ipilimumab, nivolumab, immunoembolization)
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.
Interventions:
  • Biological: Ipilimumab
  • Biological: Nivolumab
  • Drug: Embolization Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 14, 2018)
35
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Marlana Orloff, MD 215-955-8874 mmo@jefferson.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03472586
Other Study ID Numbers  ICMJE 18P.042
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
Study Sponsor  ICMJE Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Marlana Orloff, MD Sidney Kimmel Cancer Center at Thomas Jefferson University
PRS Account Thomas Jefferson University
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP