Chemotherapy After Prostatectomy (CAP) For High Risk Prostate Carcinoma

NCT ID: NCT00132301

Last Updated: 2018-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 298 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2016-09-30

Brief Summary

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.

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Arm 1: Docetaxel and Prednisone

Chemotherapy after radical prostatectomy

Group Type: ACTIVE_COMPARATOR

Docetaxel

Intervention Type: DRUG

Chemotherapy agent

Prednisone

Intervention Type: DRUG

steroid in combination with chemotherapy agent

Arm 2: Standard of care

Standard of care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Docetaxel

Chemotherapy agent

Intervention Type: DRUG

Prednisone

steroid in combination with chemotherapy agent

Intervention Type: DRUG

Other Intervention Names

Taxotere; Docecad; Deltasone, Orasone, Adasone, Prednisonum

Eligibility Criteria

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

• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Lin

Role: STUDY_CHAIR

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Bruce Montgomery, MD

Role: STUDY_CHAIR

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Locations

VA Medical Center, Birmingham

Birmingham, Alabama, United States

Southern Arizona VA Health Care System, Tucson

Tucson, Arizona, United States

Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock

North Little Rock, Arkansas, United States

VA Medical Center, Long Beach

Long Beach, California, United States

VA San Diego Healthcare System, San Diego

San Diego, California, United States

VA Medical Center, San Francisco

San Francisco, California, United States

VA Greater Los Angeles Healthcare System, West LA

West Los Angeles, California, United States

VA Connecticut Health Care System (West Haven)

West Haven, Connecticut, United States

North Florida/South Georgia Veterans Health System

Gainesville, Florida, United States

VA Medical Center, Miami

Miami, Florida, United States

James A. Haley Veterans Hospital, Tampa

Tampa, Florida, United States

VA Medical Center, Augusta

Augusta, Georgia, United States

Jesse Brown VAMC (WestSide Division)

Chicago, Illinois, United States

VA Medical Center, Lexington

Lexington, Kentucky, United States

Overton Brooks VA Medical Center, Shreveport

Shreveport, Louisiana, United States

VA Ann Arbor Healthcare System

Ann Arbor, Michigan, United States

John D. Dingell VA Medical Center, Detroit

Detroit, Michigan, United States

VA Medical Center, Minneapolis

Minneapolis, Minnesota, United States

G.V. (Sonny) Montgomery VA Medical Center, Jackson

Jackson, Mississippi, United States

VA Medical Center, Kansas City MO

Kansas City, Missouri, United States

New Mexico VA Health Care System, Albuquerque

Albuquerque, New Mexico, United States

VA Western New York Healthcare System at Buffalo

Buffalo, New York, United States

VA Medical Center, Durham

Durham, North Carolina, United States

VA Medical Center, Portland

Portland, Oregon, United States

VA Pittsburgh Health Care System

Pittsburgh, Pennsylvania, United States

Ralph H Johnson VA Medical Center, Charleston

Charleston, South Carolina, United States

VA Medical Center, Memphis

Memphis, Tennessee, United States

VA North Texas Health Care System, Dallas

Dallas, Texas, United States

Michael E. DeBakey VA Medical Center (152)

Houston, Texas, United States

VA South Texas Health Care System, San Antonio

San Antonio, Texas, United States

VA Salt Lake City Health Care System, Salt Lake City

Salt Lake City, Utah, United States

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, United States

Wlliam S. Middleton Memorial Veterans Hospital, Madison

Madison, Wisconsin, United States

VA Medical Center, San Juan

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

Lin DW, Shih MC, Aronson W, Basler J, Beer TM, Brophy M, Cooperberg M, Garzotto M, Kelly WK, Lee K, McGuire V, Wang Y, Lu Y, Markle V, Nseyo U, Ringer R, Savage SJ, Sinnott P, Uchio E, Yang CC, Montgomery RB. Veterans Affairs Cooperative Studies Program Study #553: Chemotherapy After Prostatectomy for High-risk Prostate Carcinoma: A Phase III Randomized Study. Eur Urol. 2020 May;77(5):563-572. doi: 10.1016/j.eururo.2019.12.020. Epub 2020 Jan 8.

Reference Type: DERIVED

PMID: 31924316 (View on PubMed)

Other Identifiers

553

Identifier Type: -

Identifier Source: org_study_id