CYT107 After Vaccine Treatment (Provenge) in Patients With Metastatic Hormone-Resistant Prostate Cancer
|Hormone-Resistant Prostate Cancer Metastatic Prostate Carcinoma Recurrent Prostate Carcinoma Stage IV Prostate Cancer||Biological: Glycosylated Recombinant Human Interleukin-7 Other: Laboratory Biomarker Analysis||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of Recombinant Glycosylated Human Interleukin-7 (CYT107) After Completion of Standard FDA Approved Therapy With Sipuleucel-T (Provenge®) for Patients With Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer (mCRPC)|
- Quantification of T-cell responses to PAP-GM-CSF, assessed by quantification of interferon gamma levels measured using enzyme-linked immunospot (ELISPOT) [ Time Frame: Day 70 (week 11) ]The Mann-Whitney-Wilcoxon (MWW) test will be used as part of the statistical analysis; the power is roughly equivalent to that based on the t-test.
- Change in bystander antigen specific immune responses, measured by interferon gamma production in response to various antigens as quantified by ELISPOT [ Time Frame: Baseline to up to week 53 ]Bystander antigen specific immune responses will be assessed to other ongoing and nascent antitumor responses (e.g., preferentially expressed antigen in melanoma, cancer/testis antigen 1B and/or tumor protein p53), additional tumor antigens specific to prostate cancer (e.g., PSA and/or prostate-specific membrane antigen), and memory viral responses (influenza A and cytomegalovirus, Epstein-Barr virus and influenza virus-derived peptides) using the interferon gamma ELISPOT assay.
- Change in circulating tumor cells [ Time Frame: Baseline to up to week 53 ]Enumerated by the approved Veridex assay.
- Change in number and percentage of peripheral blood mononuclear cell (PBMC) subsets and T lymphocyte subsets [ Time Frame: Baseline to up to week 53 ]The absolute change in each parameter as well as variance in change over time for each patient (mean, median, and standard error [SE]/standard deviation [SD]) will be evaluated.
- Change in PSA kinetics evaluated according to the recommendations from PSA Working Group (PSAWG) [ Time Frame: Baseline to up to week 53 ]The 95% confidence intervals should be provided.
- Change in T-cell response to PAP-GM-CSF, as measured using interferon-gamma levels quantified by ELISPOT [ Time Frame: Baseline to up to day 70 (week 11) ]
- Change in thymic function, as measured by levels of T-cell receptor rearrangement deoxyribonucleic acid (DNA) excision circles [ Time Frame: Baseline to up to week 53 ]The absolute change in parameter as well as variance in change over time for each patient (mean, median, and SE/SD) will be evaluated.
- Change in vaccine-induced antigen-specific antibody immune response to PAP, as measured by change in immunoglobulin G (IgG) and immunoglobulin M (IgM) levels quantified by standard enzyme-linked immunosorbent assay (ELISA) [ Time Frame: Baseline to up to week 53 ]
- Change in vaccine-induced antigen-specific antibody immune response to PAP-GM-CSF, as measured by change in IgG and IgM levels quantified by standard ELISA [ Time Frame: Baseline to up to week 53 ]
- Incidence of adverse events graded and reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to week 53 ]
- Overall survival [ Time Frame: Up to week 53 ]The 95% confidence intervals should be provided.
- Progression free survival assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria for measurable disease by bone scans and radiographic criteria for non-measurable bony metastasis [ Time Frame: Time from start of treatment to time of radiographic progression or death, assessed up to week 53 ]The 95% confidence intervals should be provided.
- T-cell diversity, measured by T-cell repertoire characterized by T-cell receptor (TCR) deep sequencing [ Time Frame: Week 6 ]The effects of CYT107 on T-cell diversity will be quantified.
|Study Start Date:||March 2015|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
No Intervention: Cohort I (no therapy)
Patients receive no treatment (observation) after completion of standard sipuleucel-T therapy.
Experimental: Cohort II (glycosylated recombinant human interleukin-7)
Patients receive glycosylated recombinant human interleukin-7 SC every week for 4 weeks (on days 0, 7, 14, and 21) beginning 3-7 days after completion of standard sipuleucel-T therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.
Biological: Glycosylated Recombinant Human Interleukin-7
Other Names:Other: Laboratory Biomarker Analysis
I. To determine whether CYT107 administration increases the vaccine-induced antigen-specific T-cell immune response to the sipuleucel-T fusion protein vaccine construct prostatic acid phosphatase-sargramostim (PAP-GM-CSF) (PA2024).
I. To determine whether CYT107 administration increases the vaccine-induced antigen-specific T-cell immune response to PAP.
II. To assess the character of the T-cell immune response to PAP and PA2024.
III. To determine whether CYT107 administration increases the vaccine-induced antigen-specific antibody immune responses to PAP and PA2024.
IV. To quantify the effects of CYT107 on T-cell repertoire diversity.
V. To assess the effects of CYT107 on the immune competence of patients with advanced prostate cancer.
VI. To assess the clinical efficacy and tolerability of sipuleucel-T plus CYT107 compared with sipuleucel-T alone.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
COHORT I: Patients receive no treatment (observation) after completion of standard sipuleucel-T therapy.
COHORT II: Patients receive glycosylated recombinant human interleukin-7 subcutaneously (SC) every week for 4 weeks (on days 0, 7, 14, and 21) beginning 3-7 days after completion of standard sipuleucel-T therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 53 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01881867
|United States, California|
|UC San Diego Moores Cancer Center|
|La Jolla, California, United States, 92093|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|UCSF Medical Center-Mount Zion|
|San Francisco, California, United States, 94115|
|United States, Georgia|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New Hampshire|
|Dartmouth Hitchcock Medical Center|
|Lebanon, New Hampshire, United States, 03756|
|United States, New York|
|Laura and Issac Perlmutter Cancer Center at NYU Langone|
|New York, New York, United States, 10016|
|United States, North Carolina|
|Wake Forest University Health Sciences|
|Winston-Salem, North Carolina, United States, 27157|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|
|University of Washington Medical Center|
|Seattle, Washington, United States, 98195|
|Principal Investigator:||Lawrence Fong||Cancer Immunotherapy Trials Network|