This randomized pilot clinical trial studies the side effects of tremelimumab with or without tissue cryoablation in treating patients with kidney cancer that has spread to other places in the body. Tremelimumab binds to a protein called cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which is found on the surface of T cells (a type of white blood cell). Tremelimumab may block CTLA-4 and help the immune system kill cancer cells. Cryoablation is a procedure that uses a hollow, thin tube called a cryoprobe to freeze and destroy cancer tissue. It is not yet known whether tremelimumab with or without cryoablation is effective in treating patients with kidney cancer.
PRIMARY OBJECTIVES: I. To evaluate safety of tremelimumab alone and in combination with cryoablation in patients with metastatic renal cell carcinoma (RCC). SECONDARY OBJECTIVES: I. To explore the longitudinal values for immunological variables (including cluster of differentiation \[CD\]4+ ICOS+ T cells; effector to regulatory T cell ratio; absolute lymphocyte count) following treatment with tremelimumab in patients with metastatic RCC, and evaluate difference between combination cryoablation and tremelimumab in comparison to tremelimumab alone. II. To determine the objective response rate and progression-free survival of patients treated with tremelimumab with or without cryoablation. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive tremelimumab intravenously (IV) over 60 minutes at weeks 1 and 5. Within 4-6 weeks later, patients undergo surgery or biopsy. After surgery or biopsy, patients receive tremelimumab IV every 4 weeks (Q4W) for 3 doses, and then every 12 weeks (Q12W) in the absence of disease progression or unacceptable toxicity. ARM B: Patients undergo cryoablation and receive tremelimumab IV over 60 minutes at weeks 1 (2-6 days after cryoablation) and 5. Within 4-6 weeks later, patients undergo surgery or biopsy. After surgery or biopsy, patients receive tremelimumab IV Q4W for 3 doses, and then Q12W in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30, 60, and 90 days, and then every 6 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Undergo cryoablation
Correlative studies
Undergo surgery
Given IV
M D Anderson Cancer Center
Houston, Texas, United States
Incidence of adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Safety will be recorded through the incidence of adverse events, serious adverse events and specific laboratory abnormalities (worst grade) in each treatment arm. Descriptive statistical analyses will be performed to summarize the incidence of adverse events.
Time frame: Up to 2 weeks
Incidence of extreme toxicities as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Extreme toxicities will be defined as any grade 3 or higher adverse event that is possibly, probably, or definitely related to therapy that occurs within the first two cycles of therapy with the following exceptions: any grade 3 or higher adverse event that is potentially treatable with steroids will only count as an extreme toxicity if it does not improve to grade 1 or better within 2 weeks of steroid therapy, grade 3 or 4 amylase or lipase abnormalities that are not associated with symptoms or clinical manifestations of pancreatitis, or grade 3 or 4 drug related endocrinopathies which within two weeks of presentation are adequately controlled with only physiologic hormone replacement therapy.
Time frame: Up to 2 weeks
Response rate
Descriptive statistical analyses will be performed to summarize the response rate including summary tables, scatter-plots, box-plots, proportions, 95% credible intervals, median, means, and standard deviations.
Time frame: Up to 5 years
Changes in indication markers
Differences of indication markers between arms will be compared using a t-test with transformations of non-normal data, as needed. A mixed model accounting for patient effects will be used to analyze the longitudinal data on immunological values over time.
Time frame: Up to 5 years
Progression free survival
Descriptive statistical analyses will be performed.
Time frame: Up to 5 years
Longitudinal data on immunological values over time
A mixed model accounting for patient effects will be used to analyze the longitudinal data on immunological values over time.
Time frame: Up to 13 weeks
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