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.

Condition	Intervention	Phase
Prostate Cancer	Drug: Docetaxal and Prednisone	Phase III

Further Study Details: 

Expected Total Enrollment:  636

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 prospectively randomize 636 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).

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.

Genders Eligible for Study:  Male

Criteria

Inclusion Criteria

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

2. One or more of the following poor prognostic features:

   a. tumor extension to seminal vesicle (pT3b) or bladder neck (T4)

   b. established extracapsular extension (pT3a) and Gleason Score >/= 7

   c. preoperative PSA > 20

   d. risk of biochemical progression > 50% at 5 year as determined by the Kattan nomogram

3. SWOG performance status 0-1
4. PSA nadir of </= 0.1 ng/ml within 10 weeks after prostatectomy. Patients must be randomized within 12 weeks after prostatectomy. PSA must be </= 0.1 ng/mL within 4 weeks of randomization

5. Laboratory values (no more than 4 weeks 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

6. Patients with preoperative PSA > 20 ng/mL must have a negative bone scan within 3 months of randomization
7. A valid, signed, and witnessed informed consent by the patient

Exclusion Criteria

1. Small cell histology
2. N1 disease or M1 disease
3. Clinical T3 disease prior to prostatectomy
4. Any other investigational therapy
5. An active serious infection or other serious underlying medical condition that would otherwise impair their ability to receive protocol treatment
6. A history of cancer related hypercalcemia
7. Uncontrolled heart failure
8. 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
9. Neoadjuvant androgen deprivation, chemotherapy, or radiation therapy to treat prostate carcinoma
10. Androgen deprivation prior to randomization
11. Current peripheral neuropathy of any etiology that is greater than Grade I

Please refer to this study by ClinicalTrials.gov identifier  NCT00132301

Study chairs or principal investigators

Daniel Lin, MD,  Study Chair
Robert B Montgomery,  Study Chair

Study ID Numbers:  553
Last Updated:  August 18, 2005
Record first received:  August 17, 2005
ClinicalTrials.gov Identifier:  NCT00132301
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-23