Metastatic Uveal Melanoma, Stage IV Uveal Melanoma AJCC v7
Conditions
Brief summary
This phase II trial studies how well nivolumab and ipilimumab work in treating patients with uveal melanoma that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVES: I. Overall response rate. SECONDARY OBJECTIVES: I. Progression-free survival. II. Median overall survival. III. One-year overall survival. EXPLORATORY OBJECTIVES: I. Tissue and blood correlates to define immune infiltration and signatures as a result of treatment with nivolumab plus ipilimumab. OUTLINE: INDUCTION PHASE: Patients receive nivolumab intravenously (IV) over 60 minutes and ipilimumab IV over 90 minutes during weeks 1, 4, 7, and 10. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients not experiencing disease progression or unacceptable toxicity by week 12 of the induction phase receive nivolumab IV every 2 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 60 days.
Interventions
BIOLOGICALIpilimumab
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALNivolumab
Given IV
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
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
* Willing and able to give written informed consent * History of uveal melanoma and documented metastatic disease with at least one measurable lesion is required; which is \>= 1 cm x 1 cm (on spiral computed tomography \[CT\] or equivalent) * Any number of prior therapies is allowed * White blood cell (WBC) \>= 2000/uL * Absolute neutrophil count (ANC) \>= 1500/uL * Platelets \>= 100 x 10\^3/uL * Hemoglobin \>= 9 g/dL * Creatinine =\< 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) \> 40 mL/min (using the Cockcroft-Gault formula) * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x ULN for patients without liver metastasis, =\< 5 x ULN for liver metastases * Bilirubin =\< 1.5 x ULN, (except patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/dL) * In suspected patients no active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C * Performance status Eastern Cooperative Oncology Group (ECOG) 0-1 * Baseline imaging in the form of CT chest, abdomen, pelvis with oral and intravenous contrast within 28 days of study entry; for patients with a contrast allergy, choice of alternative body imaging will be at the discretion of the investigator or his designee; magnetic resonance imaging (MRI) of the brain is only needed if clinically indicated * Prior to start of treatment must be more than 21 days elapsed from surgery, radiation therapy, or prior chemotherapy; more than 42 days elapsed from prior immune therapy including vaccines * Women of childbearing potential (WOCBP) and fertile men with partners of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized
Exclusion criteria
* Untreated primary uveal melanoma except in cases where metastatic disease is diagnosed at the time of primary disease * Metastatic uveal melanoma patients with bone-only disease * 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, breast, or prostate * Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's 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 \[e.g., Wegener's Granulomatosis\]; motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis) * Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea * Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab) * Concomitant therapy with any of the following: tamoxifen, toremifene, IL 2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids greater than physiologic replacement doses; ocular steroid use is acceptable; (a) concomitant palliative radiation for the purposes of symptom management is allowed * Women of childbearing potential (WOCBP) who: (a) are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for up to 26 weeks after cessation of study drug, or (b) have a positive pregnancy test at baseline, or (c) are pregnant or breastfeeding * Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate, Defined Per RECIST 1.1 | Up to 2 years of treatment plus 60 days from last study dose | RECIST 1.1 response is defined as \>=30% reduction in sum of the longest diameter of target lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | From date of enrollment until the date of progressive disease or date of death from any cause, whichever came first, and assessed up to 60 days after completion of study treatment, a median of 13.0 months | Time from enrollment to progressive disease or death. Progressive disease is defined per RECIST 1.1 as \>=20% increase in the sum of the longest diameter of target lesions from nadir, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Overall Survival | From date of enrollment until the date of death from any cause, a median of 13.0 months | Measured from time of enrollment to death |
| 1-year Overall Survival | Baseline up to 1 year | Measured as percentage of patients alive at 1 year from enrollment |
Countries
United States
Participant flow
Pre-assignment details
The accrual goal and dates were updated to match the new statistical design 10/2017.The enrollment changed to 39 participants. A total of 67 participants signed consent, 39 participants entered the study to participate in the trial in its current form w/combination metastatic therapy. 28 patients entered the study in its previous form when it was an adjuvant trial and then subsequently a monotherapy metastatic trial, and they are inevaluable for reporting results of the study in its current form
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Nivolumab, Ipilimumab) INDUCTION PHASE: Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes during weeks 1, 4, 7, and 10. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: Patients not experiencing disease progression or unacceptable toxicity by week 12 of the induction phase receive nivolumab IV every 2 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Ipilimumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of insurance | 1 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Nivolumab, Ipilimumab) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 0 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment United States | 35 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 35 |
| other Total, other adverse events | 32 / 35 |
| serious Total, serious adverse events | 2 / 35 |
Outcome results
Primary
Overall Response Rate, Defined Per RECIST 1.1
RECIST 1.1 response is defined as \>=30% reduction in sum of the longest diameter of target lesions
Time frame: Up to 2 years of treatment plus 60 days from last study dose
Population: 5 patients not analyzed due to lack of follow-up efficacy imaging
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Nivolumab, Ipilimumab) | Overall Response Rate, Defined Per RECIST 1.1 | Complete Response | 1 Participants |
| Treatment (Nivolumab, Ipilimumab) | Overall Response Rate, Defined Per RECIST 1.1 | Partial Response | 5 Participants |
| Treatment (Nivolumab, Ipilimumab) | Overall Response Rate, Defined Per RECIST 1.1 | Stable Disease | 11 Participants |
| Treatment (Nivolumab, Ipilimumab) | Overall Response Rate, Defined Per RECIST 1.1 | Progressive Disease | 16 Participants |
| Treatment (Nivolumab, Ipilimumab) | Overall Response Rate, Defined Per RECIST 1.1 | Unknown | 2 Participants |
Secondary
1-year Overall Survival
Measured as percentage of patients alive at 1 year from enrollment
Time frame: Baseline up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Nivolumab, Ipilimumab) | 1-year Overall Survival | 19 Participants |
Secondary
Overall Survival
Measured from time of enrollment to death
Time frame: From date of enrollment until the date of death from any cause, a median of 13.0 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Nivolumab, Ipilimumab) | Overall Survival | 19.1 Weeks |
Secondary
Progression-Free Survival
Time from enrollment to progressive disease or death. Progressive disease is defined per RECIST 1.1 as \>=20% increase in the sum of the longest diameter of target lesions from nadir, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: From date of enrollment until the date of progressive disease or date of death from any cause, whichever came first, and assessed up to 60 days after completion of study treatment, a median of 13.0 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Nivolumab, Ipilimumab) | Progression-Free Survival | 5.5 Weeks |