Biological Therapy With or Without Vaccine Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01881867
First received: June 18, 2013
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

This randomized phase II trial studies how well biological therapy with or without vaccine therapy works in treating patients with metastatic hormone-resistant prostate cancer. Biological therapies may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines may help the body build an effective immune response to kill tumor cells. It is not yet known whether biological therapy is more effective with or without vaccine therapy in treating prostate cancer.


Condition Intervention Phase
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
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 prostatic acid phosphatase-sargramostim fusion protein [ 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:
  • Increase in antigen-specific T-cell immune responses to prostatic acid phosphatase [ Time Frame: Day 70 (week 11) ] [ Designated as safety issue: No ]
  • Number and percentage of peripheral blood mononuclear cell (PBMC) subsets and T lymphocyte subsets [ Time Frame: 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.

  • Increase in the vaccine-induced antigen-specific antibody immune responses to prostatic acid phosphatase and prostatic acid phosphatase-sargramostim fusion protein [ Time Frame: Up to week 53 ] [ Designated as safety issue: No ]
  • Quantification of glycosylated recombinant human interleukin-7 on T-cell diversity [ Time Frame: Week 5 ] [ Designated as safety issue: No ]
  • Bystander antigen specific immune responses and thymic function [ Time Frame: 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.

  • PSA kinetics evaluated according to the recommendations from PSA Working Group (PSAWG) [ 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.


Estimated Enrollment: 80
Study Start Date: August 2014
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Cohort I (no therapy)
Patients receive no treatment after completion of standard sipuleucel-T therapy.
Experimental: Cohort II (glycosylated recombinant human interleukin-7)
Patients receive glycosylated recombinant human interleukin-7 SC on days 0, 7, and 14 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 (glycosylated recombinant human interleukin-7) 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 cohorts.

COHORT I: Patients receive no treatment after completion of standard sipuleucel-T therapy.

COHORT II: Patients receive glycosylated recombinant human interleukin-7 subcutaneously (SC) on days 0, 7, and 14 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 52 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
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/µL
  • Bilirubin < 1.5 x upper limit of normal (ULN)
  • Hemoglobin >= 10 g/dL
  • PSA >= 2 ng/mL
  • 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 odds ratios [ors]/orchiopexy [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) must be completed >= 8 weeks prior to enrollment
  • Patients must agree to use adequate contraception (barrier method for males) for the duration of study participation, and for four months after discontinuing therapy, because of the unknown potential risk to a gamete and/or developing embryo from this investigational therapy
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Prior chemotherapy for prostate cancer, with the exception of neoadjuvant chemotherapy, because of the potential effect of chemotherapy on the immune system
  • 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
  • No 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 (HBV) infection is not an exclusion criterion
  • No 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 because of the potential for pharmacokinetic interaction with CYT107; other trials are examining the effect of CYT107 in patients with HIV infection
  • 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
  • Prior treatment with anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) or experimental check point inhibitor such as anti-programmed-death (PD)1
  • 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 or 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
University of California Not yet recruiting
San Francisco, California, United States, 94143
Contact: Lawrence Fong    415-514-3160      
Principal Investigator: Lawrence Fong         
United States, Georgia
Winship Cancer Institute of Emory University Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Omer Kucuk    404-778-1900      
Principal Investigator: Omer Kucuk         
United States, New Hampshire
Dartmouth-Hitchcock Medical Center Not yet recruiting
Lebanon, New Hampshire, United States, 03756
Contact: John Seigne    603-650-6052      
Principal Investigator: John Seigne         
United States, New York
NYU Langone Medical Center Not yet recruiting
New York, New York, United States, 10016
Contact: Anna Ferrari    212-731-5389      
Principal Investigator: Anna Ferrari         
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Evan Yu    206-288-1152      
Principal Investigator: Evan Yu         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Lawrence Fong Cancer Immunotherapy Trials Network
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01881867     History of Changes
Other Study ID Numbers: CITN12-03, NCI-2013-00998, U01CA154967
Study First Received: June 18, 2013
Last Updated: May 28, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on July 29, 2014