Clinical trial NCT00132301: Chemotherapy After Prostatectomy (CAP) For High Risk Prostate Carcinoma
Official title: CSP #553 - Adjuvant Therapy in Prostate Carcinoma Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: multi-site clinical trial
prostate
radical prostatectomy
randomized
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Sanofi
First posted: 2005-08-19
Enrollment: 298
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Progression-Free Survival
timeFrame: Up to 100 months (centralized follow-up)
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: VA Medical Center, Birmingham
state: Alabama
city: Tucson
country: United States
facility: Southern Arizona VA Health Care System, Tucson
state: Arizona
city: North Little Rock
country: United States
facility: Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
state: Arkansas
city: Long Beach
country: United States
facility: VA Medical Center, Long Beach
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System, San Diego
state: California
city: San Francisco
country: United States
facility: VA Medical Center, San Francisco
state: California
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West LA
state: California
city: West Haven
country: United States
facility: VA Connecticut Health Care System (West Haven)
state: Connecticut
city: Gainesville
country: United States
facility: North Florida/South Georgia Veterans Health System
state: Florida
city: Miami
country: United States
facility: VA Medical Center, Miami
state: Florida
city: Tampa
country: United States
facility: James A. Haley Veterans Hospital, Tampa
state: Florida
city: Augusta
country: United States
facility: VA Medical Center, Augusta
state: Georgia
city: Chicago
country: United States
facility: Jesse Brown VAMC (WestSide Division)
state: Illinois
city: Lexington
country: United States
facility: VA Medical Center, Lexington
state: Kentucky
city: Shreveport
country: United States
facility: Overton Brooks VA Medical Center, Shreveport
state: Louisiana
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System
state: Michigan
city: Detroit
country: United States
facility: John D. Dingell VA Medical Center, Detroit
state: Michigan
city: Minneapolis
country: United States
facility: VA Medical Center, Minneapolis
state: Minnesota
city: Jackson
country: United States
facility: G.V. (Sonny) Montgomery VA Medical Center, Jackson
state: Mississippi
city: Kansas City
country: United States
facility: VA Medical Center, Kansas City MO
state: Missouri
city: Albuquerque
country: United States
facility: New Mexico VA Health Care System, Albuquerque
state: New Mexico
city: Buffalo
country: United States
facility: VA Western New York Healthcare System at Buffalo
state: New York
city: Durham
country: United States
facility: VA Medical Center, Durham
state: North Carolina
city: Portland
country: United States
facility: VA Medical Center, Portland
state: Oregon
city: Pittsburgh
country: United States
facility: VA Pittsburgh Health Care System
state: Pennsylvania
city: Charleston
country: United States
facility: Ralph H Johnson VA Medical Center, Charleston
state: South Carolina
city: Memphis
country: United States
facility: VA Medical Center, Memphis
state: Tennessee
city: Dallas
country: United States
facility: VA North Texas Health Care System, Dallas
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center (152)
state: Texas
city: San Antonio
country: United States
facility: VA South Texas Health Care System, San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: VA Salt Lake City Health Care System, Salt Lake City
state: Utah
city: Seattle
country: United States
facility: VA Puget Sound Health Care System Seattle Division, Seattle, WA
state: Washington
city: Madison
country: United States
facility: Wlliam S. Middleton Memorial Veterans Hospital, Madison
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: VA Medical Center, San Juan
Study officials:
affiliation: VA Puget Sound Health Care System Seattle Division, Seattle, WA
name: Daniel Lin
role: STUDY_CHAIR
affiliation: VA Puget Sound Health Care System Seattle Division, Seattle, WA
name: Bruce Montgomery, MD
role: STUDY_CHAIR
References:
citation: 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.