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

• ClinicalTrials.gov Identifier: NCT03472586
• Recruitment Status: Recruiting
• First Posted: March 21, 2018
• Last Update Posted: May 28, 2020
• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• 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: March 14, 2018
• First Posted Date: March 21, 2018
• Last Update Posted Date: May 28, 2020
• Actual Study Start Date: May 2, 2018
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Eye and Orbit

Intervention

• 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

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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 14, 2018): 35
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2021
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Marlana Orloff, MD; 215-955-8874; mmo@jefferson.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03472586
• Other Study ID Numbers: 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: Not Provided
• Responsible Party: Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
• Study Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborators: Bristol-Myers Squibb

Investigators

• Principal Investigator: Marlana Orloff, MD; Sidney Kimmel Cancer Center at Thomas Jefferson University

• PRS Account: Thomas Jefferson University
• Verification Date: May 2020