Clinical trial NCT00005947: Vaccine Therapy in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy
Official title: A Randomized, Double Blind, Placebo Controlled Trial of Immunotherapy With Autologous Antigen-Loaded Dendritic Cells (Provenge) for Asymptomatic Metastatic Hormome-Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage IV prostate cancer
recurrent prostate cancer
Lead sponsor: Dendreon
Sponsor class: INDUSTRY
First posted: 2004-03-05
Enrollment: 127
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to Objective Disease Progression
timeFrame: 36 months from randomization
Secondary outcomes:
measure: Overall Survival
timeFrame: From randomization to 36 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Cancer Center and Beckman Research Institute, City of Hope
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Rancho Mirage
country: United States
facility: Cancer and Blood Institute of the Desert
state: California
city: Rancho Mirage
country: United States
facility: Eisenhower Medical Center
state: California
city: San Diego
country: United States
facility: Sidney Kimmel Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Whittier
country: United States
facility: Office of Glenn Tisman
state: California
city: Orlando
country: United States
facility: Office of Barry S. Berman
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Livingston
country: United States
facility: St. Barnabas Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Albany
country: United States
facility: Albany Regional Cancer Center
state: New York
city: Bronx
country: United States
facility: Albert Einstein Comprehensive Cancer Center
state: New York
city: Garden City
country: United States
facility: Center for Medical Oncology
state: New York
city: New York
country: United States
facility: St. Vincents Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: St. Luke's-Roosevelt Hospital
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Cornell Campus
state: New York
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Columbus
country: United States
facility: AKSM Clinical Research Corporation
state: Ohio
city: Portland
country: United States
facility: Earle A. Chiles Research Institute at Providence Portland Medical Center
state: Oregon
city: Abington
country: United States
facility: Abington Hematology Oncology Associates, Incorporated
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Bryn Mawr Urology
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Office of Guy Bernstein, M.D.
state: Pennsylvania
city: Langhorne
country: United States
facility: Saint Mary Regional Cancer Center
state: Pennsylvania
city: Lansdale
country: United States
facility: North Penn Hospital
state: Pennsylvania
city: Scranton
country: United States
facility: Hematology/Oncology Associates of NE Pennsylvania, P.C.
state: Pennsylvania
city: Dallas
country: United States
facility: American Oncology Resources
state: Texas
city: Norfolk
country: United States
facility: Devine Tidewater Urology
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest
state: Washington
city: Tacoma
country: United States
facility: Hematology Oncology Northwest, P.C.
state: Washington
Study officials:
affiliation: University of California, San Francisco
name: Eric J. Small, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.