This phase I trial studies the side effects of survivin long peptide vaccine and how it works with the immune system in treating patients with neuroendocrine tumors that have spread to other parts of the body (metastatic). Tumor cells make proteins that are not usually produced by normal cells. The body sees these proteins as not belonging and sends white blood cells called T cells to attack the tumor cells that contain these proteins. By vaccinating with small pieces of these proteins called peptides, the immune system can be made to kill tumor cells. Giving survivin long peptide vaccine to patients who have survivin expression in their tumors may create an immune response in the blood that is directed against neuroendocrine tumors.
PRIMARY OBJECTIVES: I. To assess safety, tolerability and toxicity of SVN53-67/M57-KLH peptide vaccine (SurVaxM) in emulsion with incomplete Freund's adjuvant (montanide ISA 51) and given subcutaneously with sargramostim (granulocyte macrophage-colony-stimulating factor \[GM-CSF\]) in combination with a somatostatin analogue, octreotide acetate (Sandostatin LAR) in patients with survivin positive metastatic neuroendocrine tumors (NETs). SECONDARY OBJECTIVES: I. To determine clinical benefit (including complete response, partial response and stable disease as defined by Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\]1.1) at 6 months, 9 months and 12 months from study entry. II. To evaluate the immunogenicity of SurVaxM in NETs by measuring anti-survivin antibody levels and anti-tumor T-cell responses in peripheral blood. III. To determine time to progression (TTP) compared to prior to study entry, in patients with metastatic NETs treated with SurVaxM. EXPLORATORY OBJECTIVES: I. To explore immune markers associated with clinical responses to SurVaxM in peripheral blood of NETs patients. OUTLINE: Patients receive a SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant subcutaneously (SC) and sargramostim SC on day 0. Treatment repeats every 2 weeks for up to 4 doses in the absence of disease progression or unacceptable toxicity. Patients also receive octreotide acetate intramuscularly (IM) on day 0. Cycles of octreotide acetate repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients who remain free of tumor progression at 6 months and do not develop any regimen-related toxicity or serious adverse events will be eligible to receive additional doses of the vaccine and sargramostim every 3 months, for up to 1 year from the start of treatment. After completion of study treatment, patients are followed up for 3 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Given SC
Given IM
Given SC
Given SC
Roswell Park Cancer Institute
Buffalo, New York, United States
Incidence of adverse events of SVN53-67/M57-KLH peptide vaccine in combination with octreotide acetate in patients with neuroendocrine tumors
Will be assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will consider a toxicity to be an adverse event that is possibly, probably or definitely related to treatment. The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. Will be quantified using the observed rates of the adverse events, serious adverse events (SAE) and regimen limiting toxicities. Toxicity rates will be described using upper 1-sided 95% Jeffreys binomial confidence intervals.
Time frame: Up to 15 months
Immunogenicity of SVN53-67/M57-KLH peptide vaccine
Survivin-specific CD8+ responses will be measured individually at baseline, 12 weeks and end of-study. These measures will be summarized by descriptive statistics (means, medians, quartiles, etc.). Confidence intervals will be constructed for the median and the mean. Exploratory graphical analysis will be used to discover associations among variables.
Time frame: Baseline up to 15 months
Immunogenicity of SVN53-67/M57-KLH peptide vaccine
Anti-survivin antibody (humoral) responses will be measured individually at baseline, 12 weeks and end of-study. These measures will be summarized by descriptive statistics (means, medians, quartiles, etc.). Confidence intervals will be constructed for the median and the mean. Exploratory graphical analysis will be used to discover associations among variables.
Time frame: Baseline up to 15 months
Rate of progression
Will be based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 on computed tomography scan and comparison rate prior to start of treatment.
Time frame: Up to 15 months
Clinical benefit
Will be assessed with RECIST v1.1. Clinical Benefit (CB) is defined as number of patients having best overall response as complete response (CR), partial response (PR) or stable disease (SD). The estimated distribution of CB will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available.
Time frame: Up to 12 months
Time to progression (TTP)
The TTP of each patient will be compared to TTP prior to study entry. The analysis will be descriptive and reported separately for each patient.
Time frame: From enrollment to first documented progression per RECISTv1.1, assessed up to 15 months
Overall response rate (ORR)
Measured by RECIST v1.1.
Time frame: Up to 15 months
Duration of response (DOR)
Measured by RECIST v1.1.
Time frame: Up to 15 months
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