Metastatic Malignant Neoplasm in the Liver, Metastatic Uveal Melanoma, Stage IV Uveal Melanoma AJCC v7
Conditions
Brief summary
This phase II trial studies ipilimumab and nivolumab with immunoembolization in treating patients with uveal melanoma that has spread to the liver. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and 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 patients 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.
Interventions
BIOLOGICALIpilimumab
Given IV
BIOLOGICALNivolumab
Given IV
Undergo immunoembolization
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 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 other accepted and effective methods of contraception and/or to abstain from sexual intercourse for at least 23 weeks after the last dose of nivolumab and/or ipilimumab and sexually active males must use at least two other accepted and effective methods of contraception and/or to abstain from sexual intercourse for at least 31 weeks 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; liver resection and focal ablation are permitted * 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 * 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Metastasis Stabilization Rate by Response Criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) | At the end of 4th treatment cycle (Day 84 +/- 3 days). Cycles are 21 days. | Defined as complete response + partial response + stable disease. Rated by Response Evaluation Criteria in Solid Tumors version 1.1. 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Up to 1 year | Graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Toxicity rates will be estimated with corresponding 95% confidence intervals. |
| Progression Free Survival (PFS) | From the start of the treatment to confirmation of progression of disease, assessed up to 1 year | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Will be estimated using the Kaplan-Meier method. |
| Overall Survival | up to 2 years | Will be estimated using the Kaplan-Meier method. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMarlana Orloff, MD
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Ipilimumab, Nivolumab, Immunoembolization) Patients receive ipilimumab IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Patients also undergo immunoembolization on day 2. Cycles repeat every 3 weeks for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with complete response, partial response, or stable disease may receive nivolumab IV on day 1 and undergo immunoembolization on day 2. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. The interval between treatments may be extended up to every 6 weeks at the discretion of the treating physician.
Ipilimumab: Given IV
Nivolumab: Given IV
Embolization Therapy: Undergo immunoembolization | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Treatment (Ipilimumab, Nivolumab, Immunoembolization) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 14 |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 1 / 14 |
Outcome results
Primary
Hepatic Metastasis Stabilization Rate by Response Criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
Defined as complete response + partial response + stable disease. Rated by Response Evaluation Criteria in Solid Tumors version 1.1. 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.
Time frame: At the end of 4th treatment cycle (Day 84 +/- 3 days). Cycles are 21 days.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Ipilimumab, Nivolumab, Immunoembolization) | Hepatic Metastasis Stabilization Rate by Response Criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) | Complete response | 0 Participants |
| Treatment (Ipilimumab, Nivolumab, Immunoembolization) | Hepatic Metastasis Stabilization Rate by Response Criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) | Partial response | 0 Participants |
| Treatment (Ipilimumab, Nivolumab, Immunoembolization) | Hepatic Metastasis Stabilization Rate by Response Criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) | Stable Disease | 8 Participants |
| Treatment (Ipilimumab, Nivolumab, Immunoembolization) | Hepatic Metastasis Stabilization Rate by Response Criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) | Progressive disease | 5 Participants |
| Treatment (Ipilimumab, Nivolumab, Immunoembolization) | Hepatic Metastasis Stabilization Rate by Response Criteria (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) | Not Evaluated | 1 Participants |
Secondary
Incidence of Adverse Events
Graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Toxicity rates will be estimated with corresponding 95% confidence intervals.
Time frame: Up to 1 year
Secondary
Overall Survival
Will be estimated using the Kaplan-Meier method.
Time frame: From the start of the treatment to confirmation of progression of disease, assessed up to 1 year
Secondary
Progression Free Survival (PFS)
Will be estimated using the Kaplan-Meier method.
Time frame: From the start of the treatment to confirmation of progression of disease, assessed up to 1 year