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Radioembolization and Ipilimumab in Treating Patients With Uveal Melanoma With Liver Metastases

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ClinicalTrials.gov Identifier: NCT01730157
Recruitment Status : Terminated (Research Cancelled)
First Posted : November 21, 2012
Last Update Posted : March 10, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE November 12, 2012
First Posted Date  ICMJE November 21, 2012
Last Update Posted Date March 10, 2016
Study Start Date  ICMJE December 2012
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2012)
  • Number of patients that experience grade 3-4 toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 3 weeks after discontinuation of study treatment ]
  • Number of patients with an overall response of liver metastasis according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 5 years ]
    Sequential hepatic radioembolization and systemic ipilimumab will be considered potentially efficacious if >3/12 patients achieve objective responses because the upper limit of the corresponding exact 95% confidence interval will be >57%. The best overall response of liver metastases, from the start of hepatic radioembolization will be used for the efficacy analysis.
  • Overall survival [ Time Frame: From the hepatic radioembolization procedure until death, assessed up to 5 years ]
    Number of patients still alive after 5 years.
  • Progression-free (PFS) survival according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: From the hepatic radioembolization to confirmation of progression or death, assessed up to 5 years ]
    Number of patients progression free survival at 5 years. Hepatic and extrahepatic PFS will be evaluated separately.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: November 15, 2012)
Tumor genotype/phenotype Biomarkers [ Time Frame: pre-treatment (Day 0 and 28), post-hepatic radioembolization (Day 71), post ipilimumab (Year 5) ]
A number of correlative studies will be performed. Data will be analyzed longitudinally using methods such as repeated measures ANOVA; however, the primary analyses will be at specific time points (e.g., pre-treatment, post-hepatic radioembolization, post ipilimumab), and these analyses will be conducted using primarily non-parametric methods (e.g., Wilcoxon signed-rank or rank sum test). All tests will be two sided with a significance level of .05, and no adjustment for multiple comparisons will be made due to the exploratory nature of these studies.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Radioembolization and Ipilimumab in Treating Patients With Uveal Melanoma With Liver Metastases
Official Title  ICMJE Pilot Study of Sequential Hepatic Radioembolization and Systemic Ipilimumab in Patients With Uveal Melanoma Metastatic to Liver
Brief Summary This pilot clinical trial studies radioembolization and ipilimumab in treating patients with uveal melanoma with liver metastases. Radioembolization kills tumor cells by blocking the blood flow to the tumor and keeping radioactive substances near the tumor. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radioembolization together with ipilimumab may kill more tumor cells in patients with uveal melanoma
Detailed Description

PRIMARY OBJECTIVE:

I. To estimate the safety and efficacy of sequential hepatic radioembolization and systemic ipilimumab in patients with uveal melanoma metastatic to liver.

SECONDARY OBJECTIVES:

I. To evaluate effects on regulators of tumor immunity.

OUTLINE:

Patients undergo radioembolization with yttrium Y 90 glass microspheres via hepatic arterial infusion on day 1. Beginning on day 29, patients also receive ipilimumab intravenously (IV) over 90 minutes. Treatment with ipilimumab repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ciliary Body and Choroid Melanoma, Medium/Large Size
  • Ciliary Body and Choroid Melanoma, Small Size
  • Extraocular Extension Melanoma
  • Iris Melanoma
  • Liver Metastases
  • Metastatic Intraocular Melanoma
  • Recurrent Intraocular Melanoma
  • Stage IV Intraocular Melanoma
Intervention  ICMJE
  • Biological: ipilimumab
    Given IV
    Other Names:
    • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
    • MDX-010
    • MDX-CTLA-4
    • monoclonal antibody CTLA-4
  • Radiation: yttrium Y 90 glass microspheres
    Given via hepatic arterial infusion
    Other Name: TheraSphere
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE Experimental: Treatment (yttrium Y 90 glass microspheres, ipilimumab)
Patients undergo radioembolization with yttrium Y 90 glass microspheres via hepatic arterial infusion on day 1. Beginning on day 29, patients also receive ipilimumab IV over 90 minutes. Treatment with ipilimumab repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Biological: ipilimumab
  • Radiation: yttrium Y 90 glass microspheres
  • Other: laboratory biomarker analysis
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 Terminated
Actual Enrollment  ICMJE
 (submitted: March 9, 2016)
6
Original Estimated Enrollment  ICMJE
 (submitted: November 15, 2012)
12
Actual Study Completion Date  ICMJE February 2016
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologic diagnosis of metastatic uveal melanoma; the tumor biopsy/aspiration must be available for review
  • Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
  • Patients must have liver metastasis
  • No more than one prior systemic therapeutic regimen; this includes chemotherapy, biologic therapy, biochemotherapy, or investigational treatment; this does not include any therapies given in the adjuvant setting
  • No concomitant therapy with any of the following: interleukin-2 (IL-2), interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids; must have been discontinued > 4 weeks
  • Patients with prior hepatic embolization procedures are eligible as long as they are candidates for repeat procedures and they have demonstrated progressive disease
  • No infection with human immunodeficiency virus (HIV); due to the mechanism of action of ipilimumab, activity and side effects in an immune compromised patient are unknown
  • No active infection with hepatitis B
  • No active or chronic infection with hepatitis C
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Women must not be pregnant or breast-feeding due to unknown effects of treatments on the unborn fetus; all women of childbearing potential must have a blood test within 72 hours prior to randomization to rule out pregnancy; women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception; women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized; sexually mature females who have not undergone a hysterectomy or who have not been postmenopausal naturally for at least 24 consecutive months (i.e., who have had menses at some time in the preceding 24 consecutive months) are considered to be of childbearing potential; women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential
  • White blood cell (WBC) >= 2000/uL
  • Absolute neutrophil count (ANC) >= 1500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8 g/dL
  • Creatinine =< 3.0 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
  • Bilirubin =< 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  • Albumin >= 3 g/dL

Exclusion Criteria:

  • Patients are excluded if they have liver tumor volume > 50%
  • Patients are excluded if they have any history of central nervous system (CNS) metastases
  • Patients are excluded if they have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix
  • Patients are excluded if they have a history of autoimmune disease, as follows: patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]); patients with motor neuropathy considered of autoimmune origin (e.g., Guillain- Barre syndrome and myasthenia gravis) are excluded; patients with a history of autoimmune thyroiditis are eligible if their current thyroid disorder is treated and stable with replacement or other medical therapy
  • Patients are excluded for any underlying medical or psychiatric condition, which in the opinion of the investigator, will make treatment hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea
  • Patients are excluded if they have a history of prior treatment with ipilimumab or prior tumor necrosis factor receptor superfamily, member 9 (CD137) agonist or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor or agonist
  • Patients are excluded for receiving any non-oncology vaccine therapy used for prevention of infectious diseases for up to four weeks (28 days) prior to or after any dose of ipilimumab
  • Patients are excluded if they have any concurrent medical condition requiring the use of systemic steroids (the use of inhaled or topical steroids is permitted)
  • Patients are excluded if they have a functional organ transplant
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01730157
Other Study ID Numbers  ICMJE CASE1612
NCI-2012-02203 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Michael McNamara, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date March 2016

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