This phase I pilot trial studies the side effects of stereotactic radiosurgery and nivolumab in treating patients with newly diagnosed melanoma that has spread to the brain or spine. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor to more precisely target the cancer. Monoclonal antibodies, such as nivolumab may interfere with the ability of tumor cells to grow and spread. Giving stereotactic radiosurgery together with nivolumab may be a better treatment for melanoma.
PRIMARY OBJECTIVES: I. To assess the safety profile of stereotactic radiosurgery with nivolumab in combination to treat patients with newly diagnosed melanoma brain or spinal metastases. SECONDARY OBJECTIVES: I. To estimate local control rate in brain and spine. II. To estimate systematic control rate. III. To estimate progression-free survival. TERTIARY OBJECTIVES: I. To explore peripheral blood immune response during and after treatment. OUTLINE: Patients receive nivolumab intravenously (IV) over 60 minutes on day 1. Patients then undergo stereotactic radiosurgery on day 8 per standard of care. Courses with nivolumab repeats every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 10 weeks, and then every 3 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Correlative studies
Given IV
Undergo stereotactic radiosurgery
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Incidence of serious adverse events (SAE) graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.0
All SAEs will be tabulated by type and grade. Proportion of individual type of SAE event will be estimated using the binomial distribution along with 95% confidence interval (exact method).
Time frame: Up 12 weeks after first dose of study treatment
Changes in the immune profile of peripheral blood during and after treatment with nivolumab in combination with stereotactic radiosurgery (immune response)
Correlative outcomes will be summarized using descriptive statistics. Logistic regression model will be considered to explore potential association between the control rate and correlative outcomes.
Time frame: Baseline to up to 12 months
Incidence of toxicity graded according to the NCI CTC 4.0
Toxicity events will be tabulated by type and grade. The severity and frequency of the toxicity will be tabulated by the tested dose or doses using descriptive statistics. The proportions of patient who experienced grade 3 or above toxicities will be estimated, along with 95% confidence intervals by each type of toxicity.
Time frame: Up to 30 days after completion of study treatment
Local control rate in brain defined as no change in number of lesions at initial treatment in the brain and change on size of targeted lesion is =< 25% from initial measurement
The local control rate will be estimated using binomial distribution along with 95% confidence. The duration of the local control will be summarized using median and range.
Time frame: From date of initial nivolumab treatment to first date that progressive disease is objectively documented, assessed up to 3 years
Progression-free survival according to Response Evaluation Criteria in Solid Tumors criteria 1.1
The probability of progression-free survival will be estimated using the Kaplan-Meier method.
Time frame: From the date of initial diagnosis (at surgery) to the date of progressive disease was defined (documented), assessed up to 3 years
Systematic control rate in spine defined as no change in number of lesions at initial treatment in the spine and change on size of targeted lesion is =< 25% from initial measurement
The systematic control rate will be estimated using binomial distribution along with 95% confidence.
Time frame: Up to 3 years
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