Chemotherapy After Prostatectomy (CAP) For High Risk Prostate Carcinoma (CAP)

May 25, 2018 updated by: VA Office of Research and Development

CSP #553 - Adjuvant Therapy in Prostate Carcinoma Treatment

VA Cooperative Study #553 is designed to prospectively evaluate the efficacy of early adjuvant chemotherapy using docetaxel and prednisone added to the standard of care for patients who are potentially cured by radical prostatectomy but who are at high risk for relapse. The standard of care is surveillance, with the addition of androgen deprivation at the time of biochemical relapse. This study will assess the effect of adding early chemotherapy to the standard of care on progression free survival in Veterans at high risk for progression after prostatectomy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

VA Cooperative Study #553 is designed to prospectively evaluate the efficacy of early adjuvant chemotherapy using docetaxel and prednisone added to the standard of care for patients who are potentially cured by radical prostatectomy but who are at high risk for relapse. The standard of care is surveillance, with the addition of androgen deprivation at the time of biochemical relapse. This study will assess the effect of adding early chemotherapy to the standard of care on progression free survival in Veterans at high risk for progression after prostatectomy.

The ability of radical prostatectomy to cure prostate cancer and to therefore prevent the morbidity and mortality associated with progression to metastatic disease depends on effectively treating both local and potential systemic disease. In the United States alone, over 80,000 men per year are treated with prostatectomy to cure their disease. Because 20% of these men will be found to have locally advanced or high-grade disease, they will be at risk for relapse and morbidity from their prostate cancer. Although androgen deprivation, radiation therapy, and chemotherapy have been considered potentially effective adjuvant modalities for localized prostate cancer, there are no randomized studies that support the utility of any of these treatments as a standard of care. Ultimately, it is androgen independent prostate cancer, which causes morbidity for these patients. Docetaxel based chemotherapy has been shown to prolong survival and induce responses in up to 80% of patients with androgen independent disease, generating enthusiasm for the use of chemotherapy early in the treatment of prostate cancer. This study is designed to test the value of adjuvant chemotherapy in improving progression free survival, which is critical in preventing morbidity and mortality from relapse in patients with clinically localized, but high risk, prostate cancer.

After patients are stratified for PSA, Gleason score, tumor stage, the presence of positive margins, and the planned use of adjuvant radiation therapy, this study will randomized 300 patients from 30 VA sites, after prostatectomy, to the standard of care or to docetaxel and prednisone administered every 3 weeks for 18 weeks. Patients would then be observed with PSA for a minimum of one and a maximum of five years. The study is designed with 90% power to detect a reduction in the 5-year progression rate from 60% to 45% (15% absolute difference, 25% relative difference).

At the end of the study period (October 31, 2012), the patients in the study will continue to be passively followed for three more years. The follow-up study involved centralized remote access of the participants' medical records to obtain information on PSA levels and study endpoints.

Prostate cancer is the leading cause of malignancy for Veterans, and the second leading cause of death. Patients with high risk, localized disease account for 70% of all cancer deaths in patients treated for cure with radical prostatectomy. Effective adjuvant therapy is critical to reducing suffering and death from prostate cancer. The VA Cooperative Studies Program is uniquely placed to address this question. The VA has a longstanding history of important studies in prostate cancer, which have significantly changed the way urologic oncologists treat patients with this disease. The incidence of prostate cancer in our older, male population is substantial, the number of Veterans treated with prostatectomy continues to rise, and the incidence of high risk prostate cancer in Veterans is greater than that typically found in the community. For all of these reasons, carrying out this study within the VA through the VA Cooperative Studies Program is the optimal way to determine whether adjuvant chemotherapy will benefit men with high risk prostate cancer.

Study Type

Interventional

Enrollment (Actual)

298

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00921
        • VA Medical Center, San Juan
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • VA Medical Center, Birmingham
    • Arizona
      • Tucson, Arizona, United States, 85723
        • Southern Arizona VA Health Care System, Tucson
    • Arkansas
      • North Little Rock, Arkansas, United States, 72114-1706
        • Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
    • California
      • Long Beach, California, United States, 90822
        • VA Medical Center, Long Beach
      • San Diego, California, United States, 92161
        • VA San Diego Healthcare System, San Diego
      • San Francisco, California, United States, 94121
        • VA Medical Center, San Francisco
      • West Los Angeles, California, United States, 90073
        • VA Greater Los Angeles Healthcare System, West LA
    • Connecticut
      • West Haven, Connecticut, United States, 06516
        • VA Connecticut Health Care System (West Haven)
    • Florida
      • Gainesville, Florida, United States, 32608
        • North Florida/South Georgia Veterans Health System
      • Miami, Florida, United States, 33125
        • VA Medical Center, Miami
      • Tampa, Florida, United States, 33612
        • James A. Haley Veterans Hospital, Tampa
    • Georgia
      • Augusta, Georgia, United States, 30904
        • VA Medical Center, Augusta
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Jesse Brown VAMC (WestSide Division)
    • Kentucky
      • Lexington, Kentucky, United States, 40502
        • VA Medical Center, Lexington
    • Louisiana
      • Shreveport, Louisiana, United States, 71101
        • Overton Brooks VA Medical Center, Shreveport
    • Michigan
      • Ann Arbor, Michigan, United States, 48113
        • VA Ann Arbor Healthcare System
      • Detroit, Michigan, United States, 48201
        • John D. Dingell VA Medical Center, Detroit
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • VA Medical Center, Minneapolis
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • G.V. (Sonny) Montgomery VA Medical Center, Jackson
    • Missouri
      • Kansas City, Missouri, United States, 64128
        • VA Medical Center, Kansas City MO
    • New Mexico
      • Albuquerque, New Mexico, United States, 87108-5153
        • New Mexico VA Health Care System, Albuquerque
    • New York
      • Buffalo, New York, United States, 14215
        • VA Western New York Healthcare System at Buffalo
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • VA Medical Center, Durham
    • Oregon
      • Portland, Oregon, United States, 97201
        • VA Medical Center, Portland
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15240
        • VA Pittsburgh Health Care System
    • South Carolina
      • Charleston, South Carolina, United States, 29401-5799
        • Ralph H Johnson VA Medical Center, Charleston
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • VA Medical Center, Memphis
    • Texas
      • Dallas, Texas, United States, 75216
        • VA North Texas Health Care System, Dallas
      • Houston, Texas, United States, 77030
        • Michael E. DeBakey VA Medical Center (152)
      • San Antonio, Texas, United States, 78229
        • VA South Texas Health Care System, San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84148
        • VA Salt Lake City Health Care System, Salt Lake City
    • Washington
      • Seattle, Washington, United States, 98108
        • VA Puget Sound Health Care System Seattle Division, Seattle, WA
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • Wlliam S. Middleton Memorial Veterans Hospital, Madison

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • A histologic diagnosis of cT1-T2 primary adenocarcinoma of the prostate prior to prostatectomy, with lymph node dissection at time of radical prostatectomy

  • One or more of the following poor prognostic features:

    • tumor extension to seminal vesicle (pT3b) or bladder neck (T4)
    • established extracapsular extension (pT3a) and Gleason Score >= 7
    • organ confined (pT2) with positive surgical margin and Gleason 8-10
    • preoperative PSA > 20
  • SWOG performance status 0-1
  • PSA nadir of <= 0.1 ng/ml up to 30 days prior to randomization. Patients must be randomized within 120 days after prostatectomy.

  • Laboratory values (no more than 30 days before randomization) must be as follows:

    • Absolute granulocyte count: >= 1,500/mm3
    • Platelets: >= 100,000/mm3
    • Hemoglobin: >= 10 g/dL
    • Serum Creatinine: <= 1.5 x ULN
    • AST: <= 1.5 x ULN
    • ALT: <= 1.5 x ULN
    • Serum Calcium: <= ULN
    • Total Bilirubin: <=ULN
    • Plasma Phosphorus Level: <= 6 mg/dl
  • Patients with preoperative PSA > 20 ng/mL must have a negative bone scan within 120 days of randomization
  • A valid, signed, and witnessed informed consent by the patient

Exclusion Criteria:

  • Small cell histology
  • N1 disease or M1 disease
  • Clinical T3 disease prior to prostatectomy
  • Any other investigational therapy
  • An active serious infection or other serious underlying medical condition that would otherwise impair their ability to receive protocol treatment
  • A history of cancer related hypercalcemia
  • Uncontrolled heart failure
  • Prior malignancy other than curatively treated squamous cell or basal cell carcinoma of the skin. If another malignancy has been treated and there is no evidence of relapse > 5 years from the time of treatment, patients are eligible
  • Androgen deprivation, chemotherapy, or radiation therapy to treat prostate carcinoma
  • Current peripheral neuropathy of any etiology that is greater than Grade I

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm 1: Docetaxel and Prednisone
Chemotherapy after radical prostatectomy
Drug: Docetaxel
Chemotherapy agent
Other Names:
  • Taxotere
  • Docecad
Drug: Prednisone
steroid in combination with chemotherapy agent
Other Names:
  • Deltasone, Orasone, Adasone, Prednisonum
No Intervention: Arm 2: Standard of care
Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Progression-Free Survival
Time Frame: Up to 100 months (centralized follow-up)
The primary objective of this study is to determine whether adding early chemotherapy based on docetaxel plus prednisone compared to standard of care alone reduces disease progression as evidenced by detectable PSA in high risk patients with prostate cancer who have undergone radical prostatectomy.
Up to 100 months (centralized follow-up)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Collaborators

Sanofi

Investigators

  • Study Chair: Daniel Lin, VA Puget Sound Health Care System Seattle Division, Seattle, WA
  • Study Chair: Bruce Montgomery, MD, VA Puget Sound Health Care System Seattle Division, Seattle, WA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

October 1, 2015

Study Completion (Actual)

September 1, 2016

Study Registration Dates

First Submitted

August 17, 2005

First Submitted That Met QC Criteria

August 18, 2005

First Posted (Estimate)

August 19, 2005

Study Record Updates

Last Update Posted (Actual)

June 25, 2018

Last Update Submitted That Met QC Criteria

May 25, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 553

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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