Vaccine Therapy in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy

A Randomized, Double Blind, Placebo Controlled Trial of Immunotherapy With Autologous Antigen-Loaded Dendritic Cells (Provenge) for Asymptomatic Metastatic Hormome-Refractory Prostate Cancer

Rationale: Vaccines may make the body build an immune response to kill tumor cells. It is not yet known if vaccine therapy is effective for prostate cancer.

Purpose: Randomized phase III trial to determine the effectiveness of vaccine therapy in treating patients who have metastatic prostate cancer that has not responded to hormone therapy.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Biological: sipuleucel-T; Biological: Placebo

Detailed Description

Objectives:

I. Compare the time to progression, time to development of disease-related pain, and incidence of grade 3 or worse treatment-related adverse events in patients with asymptomatic metastatic hormone refractory adenocarcinoma of the prostate treated with APC8015 versus control infusion. II. Compare response rate and duration of response in these patients.

Outline: This is a randomized study. Patients are randomized to one of two treatment arms. Arm I: Autologous dendritic cell precursors (ADCP) are harvested on weeks 0, 2, and 4. Patients receive APC8015 comprised of ADCP activated with prostatic acid phosphatase-sargramostim (GM-CSF) fusion protein IV over 30 minutes beginning 2 days after each harvest for a total of 3 infusions. Arm II: ADCP are harvested as in arm I. Patients receive unactivated ADCP IV over 30 minutes beginning 2 days after each harvest for a total of 3 infusions. Pain is assessed weekly for up to 3 years or until 4 weeks after objective disease progression. Patients are followed monthly for up to 3 years or until disease progression. At the time of disease progression, patients treated on arm II may receive treatment on Protocol D9903.

Projected Accrual: A total of 120 patients (80 in arm I and 40 in arm II) will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • Cancer Center and Beckman Research Institute, City of Hope
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Rancho Mirage, California, United States, 92270
      • Eisenhower Medical Center
    • Rancho Mirage, California, United States, 92270
      • Cancer and Blood Institute of the Desert
    • San Diego, California, United States, 92121
      • Sidney Kimmel Cancer Center
    • San Francisco, California, United States, 94143-0128
      • UCSF Cancer Center and Cancer Research Institute
    • Whittier, California, United States, 90601
      • Office of Glenn Tisman
  • Florida
    • Orlando, Florida, United States, 32806
      • Office of Barry S. Berman
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Livingston, New Jersey, United States, 07039
      • St. Barnabas Medical Center
    • Morristown, New Jersey, United States, 07962-1956
      • Morristown Memorial Hospital
  • New York
    • Albany, New York, United States, 12208
      • Albany Regional Cancer Center
    • Bronx, New York, United States, 10461
      • Albert Einstein Comprehensive Cancer Center
    • Garden City, New York, United States, 11530
      • Center for Medical Oncology
    • New York, New York, United States, 10011
      • St. Vincents Comprehensive Cancer Center
    • New York, New York, United States, 10016
      • NYU School of Medicine's Kaplan Comprehensive Cancer Center
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital - Cornell Campus
    • New York, New York, United States, 10019
      • St. Luke's-Roosevelt Hospital
    • Rochester, New York, United States, 14642
      • University of Rochester Cancer Center
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • Ohio
    • Columbus, Ohio, United States, 43214
      • AKSM Clinical Research Corporation
  • Oregon
    • Portland, Oregon, United States, 97213-2967
      • Earle A. Chiles Research Institute at Providence Portland Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Hematology Oncology Associates, Incorporated
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Urology
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Office of Guy Bernstein, M.D.
    • Langhorne, Pennsylvania, United States, 19047
      • Saint Mary Regional Cancer Center
    • Lansdale, Pennsylvania, United States, 19446-1200
      • North Penn Hospital
    • Scranton, Pennsylvania, United States, 18510
      • Hematology/Oncology Associates of NE Pennsylvania, P.C.
  • Texas
    • Dallas, Texas, United States, 75246
      • American Oncology Resources
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Devine Tidewater Urology
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest
    • Tacoma, Washington, United States, 98405
      • Hematology Oncology Northwest, P.C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria include:

• Metastatic disease as evidenced by soft tissue and/or bony metastases.
• Baseline PSA value of at least 5 ng/mL. All subjects must have stable or rising PSA.
• Tumor progression after hormonal therapy.
• Hormonal therapy consisting of castration by orchiectomy or LHRH agonists for treatment of prostate cancer. Castration levels of testosterone (< 50 ng/dL) must be documented for all subjects including subjects who underwent orchiectomy as therapy for cancer of the prostate.
• A subject is eligible if he initially responded to antiandrogen withdrawal (> 25% decrease in PSA) but at the time of registration demonstrated tumor progression. A subject is eligible if he failed to respond to antiandrogen withdrawal.
• Subjects have no cancer-related pain and do not regularly require analgesics for cancer-related pain.
• ECOG Performance Status of 0 or 1.
• Life expectancy of at least 16 weeks.
• Adequate hematologic, renal, and liver function.

Exclusion Criteria include:

• Visceral organ metastases (e.g., liver, lung, brain) or cytologically positive effusions (e.g., pleural effusions or ascites).
• Metastatic disease expected to be in need of radiation therapy within 4 months.
• Concurrent therapy with experimental agents.
• Systemic corticosteroids at doses greater than 40 mg hydrocortisone per day for any reason other than treatment of prostate cancer within the previous 6 months without prior approval.

Please note that there are additional eligibility criteria. The study center will determine if you meet all of the criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Biological: Placebo; Approximately one-third of the autologous quiescent antigen presenting cells (APCs) prepared from a single leukapheresis procedure. A course of therapy consists of 3 complete doses given at approximately 2-week intervals.
Active Comparator: sipuleucel-T	Biological: sipuleucel-T; Autologous peripheral blood mononuclear cells, including antigen presenting cells, that have been activated in vitro with a recombinant fusion protein, PAP-GM-CSF. Treatment consist of 3 doses administered approximately 2 weeks apart.; Other Names: APC8015, Provenge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Objective Disease Progression	The time to objective disease progression in patients with asymptomatic metastatic hormone-refractory prostate cancer treated with APC8015 (sipuleucel-T).	36 months from randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall Survival	From randomization to 36 months

Collaborators and Investigators

• Sponsor: Dendreon

Publications and helpful links

General Publications

• Ju M, Fan J, Zou Y, Yu M, Jiang L, Wei Q, Bi J, Hu B, Guan Q, Song X, Dong M, Wang L, Yu L, Wang Y, Kang H, Xin W, Zhao L. Computational Recognition of a Regulatory T-cell-specific Signature With Potential Implications in Prognosis, Immunotherapy, and Therapeutic Resistance of Prostate Cancer. Front Immunol. 2022 Jun 23;13:807840. doi: 10.3389/fimmu.2022.807840. eCollection 2022.
• Small EJ, Higano CS, Kantoff PW, Whitmore JB, Frohlich MW, Petrylak DP. Time to disease-related pain and first opioid use in patients with metastatic castration-resistant prostate cancer treated with sipuleucel-T. Prostate Cancer Prostatic Dis. 2014 Sep;17(3):259-64. doi: 10.1038/pcan.2014.21. Epub 2014 Jun 24.
• Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009 Aug 15;115(16):3670-9. doi: 10.1002/cncr.24429.
• Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006 Jul 1;24(19):3089-94. doi: 10.1200/JCO.2005.04.5252.

Study record dates

Study Major Dates

• Study Start: November 1, 1999
• Primary Completion (Actual): September 1, 2004
• Study Completion (Actual): September 1, 2004

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: March 4, 2004
• First Posted (Estimate): March 5, 2004

Study Record Updates

• Last Update Posted (Estimate): November 1, 2010
• Last Update Submitted That Met QC Criteria: October 8, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: stage IV prostate cancer; recurrent prostate cancer; adenocarcinoma of the prostate
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: D9901 CDR0000067868; DEN-D9901; NCI-G00-1789