CYT107 After Vaccine Treatment (Provenge) in Patients With Metastatic Hormone-Resistant Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Cancer Immunotherapy Trials Network
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01881867
First received: June 18, 2013
Last updated: June 6, 2016
Last verified: June 2016
  Purpose
This randomized phase II trial studies how well glycosylated recombinant human interleukin-7 (CYT107) after vaccine therapy works in treating patients with hormone-resistant prostate cancer that has spread to other areas of the body or has not responded to at least one type of treatment. Biological therapies, such as glycosylated recombinant human interleukin-7, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines made from white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. It is not yet known whether glycosylated recombinant human interleukin-7 works better with or without vaccine therapy in treating prostate cancer.

Condition Intervention Phase
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 Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: Up to week 53 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The effects of CYT107 on T-cell diversity will be quantified.


Estimated Enrollment: 80
Study Start Date: September 2013
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Given SC
Other Names:
  • CYT107
  • Glycosylated rhIL-7
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)
  • Patients must have successfully completed therapy with sipuleucel-T within 3-7 days of planned CYT107 study drug treatment
  • Assessable disease with a positive bone scan and/or measurable disease on computed tomography (CT) scan and/or magnetic resonance imaging (MRI) of the abdomen and pelvis
  • Prior orchiectomy or must be on ongoing luteinizing hormone-releasing hormone (LHRH) agonist or antagonist (e.g., degarelix) therapy
  • No ongoing anti-androgen therapy; patients must be off anti-androgen therapy for at least 30 days
  • Patients receiving any other hormonal therapy, including any dose of megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease prostate specific antigen (PSA) levels (e.g. saw palmetto, PC-SPES), or any systemic corticosteroid, must discontinue the agent for at least 30 days prior to study treatment
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Bilirubin < 1.5 x upper limit of normal (ULN)
  • Hemoglobin >= 10 g/dL
  • Platelets >= 100,000/mcL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
  • Creatinine clearance >= 60 mL/min by the Cockcroft-Gault equation
  • Testosterone =< 50 ng/dL (documented at any time while on LHRH agonist or antagonists or s/p orchiectomy)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or a Karnofsky performance status of >= 80%
  • Life expectancy of at least 6 months
  • Prior local radiation therapy must be completed at least 30 days prior to enrollment and the patient must have recovered from all toxicity
  • Prior "systemic" radiopharmaceuticals (strontium, samarium, radium 223 dichloride) must be completed >= 8 weeks prior to enrollment
  • Patients must agree to use 2 methods of adequate contraception for the duration of study participation, and for four months after discontinuing therapy
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Prior chemotherapy for castration resistant prostate cancer; neoadjuvant chemotherapy and chemotherapy given for hormone sensitive prostate cancer are allowed
  • Prior investigational immunotherapy
  • Prostate cancer pain requiring regularly scheduled narcotics
  • Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression
  • Current treatment with systemic steroid therapy (inhaled/topical steroids are acceptable); systemic corticosteroids must be discontinued for at least 30 days prior to first CYT107 injection
  • Known central nervous system metastases
  • Documented cirrhosis or documented acute hepatitis; Note: a positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antibody [HBsAb] positive and hepatitis B core antibody [HBcAb] negative), or a fully resolved acute hepatitis B virus (HBV) infection is not an exclusion criterion
  • History of severe asthma, as defined by prior or current use of systemic corticosteroids for disease control, with the exception of physiological replacement doses of cortisone acetate or equivalent, as defined by a dose of 10 mg or less
  • Medical or psychiatric illness that would, in the opinion of the investigator, preclude participation in the study or the ability of patients to provide informed consent for themselves
  • Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
  • Concurrent or prior malignancy except for the following:

    • Adequately treated basal or squamous cell skin cancer
    • Adequately treated stage I or II cancer from which the patient is currently in complete remission
    • Any other cancer from which the patient has been disease-free for 5 years
  • Known human immunodeficiency virus (HIV) or other history of immunodeficiency disorder; HIV-positive patients on combination antiretroviral therapy are ineligible
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g. infectious) illness
  • Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of CYT107 hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to CYT107
  • Patients who have received prior immunosuppressive therapy within 30 days prior to enrollment
  • Active (as defined by requiring immunosuppressive therapy) or history of clinically significant autoimmune disease (as defined by previously requiring immunosuppressive therapy)
  • Patients who have received hepatotoxic drugs less than 7 days prior to enrollment
  • Patients who have received prior biologic agents less than 30 days prior to enrollment
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients who have a history of any hematopoietic malignancy
  • History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume [FEV] > 60% of predicted for height and age required in patients with prolonged smoking history or symptoms of respiratory dysfunction)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01881867

Locations
United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Frederick E. Millard    858-822-5354    cancercto@ucsd.edu   
Principal Investigator: Frederick E. Millard         
USC / Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Tanya B. Dorff    323-865-0451      
Principal Investigator: Tanya B. Dorff         
UCSF Medical Center-Mount Zion Recruiting
San Francisco, California, United States, 94115
Contact: Lawrence Fong    415-514-3160    lfong@medicine.ucsf.edu   
Principal Investigator: Lawrence Fong         
United States, Georgia
Emory University/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Omer Kucuk    404-778-1868      
Principal Investigator: Omer Kucuk         
Emory University/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Omer Kucuk    404-778-1900    okucuk@emory.edu   
Principal Investigator: Omer Kucuk         
United States, Illinois
University of Chicago Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Russell Z. Szmulewitz    773-834-7424      
Principal Investigator: Russell Z. Szmulewitz         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Lauren C. Harshman    877-442-3324      
Principal Investigator: Lauren C. Harshman         
United States, New Hampshire
Dartmouth Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: John D. Seigne    800-639-6918    cancer.research.nurse@dartmouth.edu   
Principal Investigator: John D. Seigne         
United States, New York
Laura and Issac Perlmutter Cancer Center at NYU Langone Recruiting
New York, New York, United States, 10016
Contact: Anna C. Ferrari    212-731-5389      
Principal Investigator: Anna C. Ferrari         
United States, North Carolina
Wake Forest University Health Sciences Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Rhonda L. Bitting    336-713-6771      
Principal Investigator: Rhonda L. Bitting         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: J. P. Monk    800-293-5066    Jamesline@osumc.edu   
Principal Investigator: J. P. Monk         
United States, Pennsylvania
University of Pittsburgh Cancer Institute (UPCI) Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Leonard J. Appleman    412-647-8073      
Principal Investigator: Leonard J. Appleman         
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Evan Y. Yu    206-288-1152    evanyu@u.washington.edu   
Principal Investigator: Evan Y. Yu         
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Evan Y. Yu    800-804-8824      
Principal Investigator: Evan Y. Yu         
University of Washington Medical Center Active, not recruiting
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Cancer Immunotherapy Trials Network
Investigators
Principal Investigator: Lawrence Fong Cancer Immunotherapy Trials Network
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01881867     History of Changes
Other Study ID Numbers: CITN12-03  NCI-2013-00998  CITN12-03 IL7  CITN12-03  CITN12-03  U01CA154967 
Study First Received: June 18, 2013
Last Updated: June 6, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Prostatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on July 28, 2016