A Phase III Study of Neoadjuvant Docetaxel and Androgen Suppression Plus Radiation Therapy Versus Androgen Suppression Alone Plus Radiation Therapy for High-Risk Localized Adenocarcinoma of the Prostate (DART)
18 Years
N/A
Male
Prostate Cancer
Trial Information
A Phase III Study of Neoadjuvant Docetaxel and Androgen Suppression Plus Radiation Therapy Versus Androgen Suppression Alone Plus Radiation Therapy for High-Risk Localized Adenocarcinoma of the Prostate (DART)
OBJECTIVES:
Primary
- To compare disease-free survival rates in patients with high-risk localized
adenocarcinoma of the prostate treated with androgen suppression therapy and
radiotherapy with vs without docetaxel.
Secondary
- To compare overall survival.
- To compare time to biochemical disease progression.
- To compare time to local disease progression.
- To compare time to distant disease progression.
- To compare time to next anticancer therapy.
- To compare progression-free survival.
- To compare degree of prostate-specific antigen (PSA) suppression prior to radiotherapy.
- To compare quality of life (QOL) using EORTC QLQ C30 and EORTC QLQ PR25 questionnaires
and a trial-specific checklist.
- To compare the nature, severity, and frequency of adverse events.
OUTLINE: This is a multicenter study. Patients are stratified according to Gleason score (≤
7 vs ≥ 8), baseline prostate-specific antigen (PSA) (> 20 ng/mL vs ≤ 20 ng/mL), and
participating center. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive androgen suppression therapy comprising oral flutamide three
times daily or oral bicalutamide once daily for 4 weeks AND leuprolide subcutaneously
(SC) or intramuscularly every 1-6 months, buserelin SC every 2 or 3 months, or
goserelin SC every 1 or 3 months for 3 years. Patients also receive docetaxel IV over
60 minutes on day 1. Treatment with docetaxel repeats every 21 days for up to 4
courses. Beginning at least 4 weeks after completion of chemotherapy, patients undergo
pelvic radiotherapy once daily 5 days a week for up to 8 weeks.
- Arm II: Patients receive androgen suppression therapy and undergo pelvic radiotherapy
as in arm I.
Patients complete quality of life questionnaires at baseline, periodically during treatment,
and then every 6 months for 5 years.
After completion of study treatment, patients are followed at 3 and 6 months, every 6 months
for 5 years, and then annually thereafter.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the prostate
- Localized (N0, M0) disease
- No small cell or transitional cell carcinoma in the biopsy specimen
- Considered to be at high risk for recurrence based on the presence of at least one of
the following adverse prognostic features:
- T stage ≥ 3a
- Gleason score ≥ 8
- Baseline prostate-specific antigen (PSA) > 20 ng/mL
- Deemed to be an appropriate candidate for chemotherapy, as assessed by a medical
oncologist
- Negative pelvic and para-aortic lymph nodes on CT scan or MRI of the abdomen and
pelvis
- Any lymph node appearing ≥ 1.5 cm on CT scan or MRI must be histologically
negative by either needle aspirate or lymph node dissection
- No metastases by chest x-ray and bone scan
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 10.0 g/dL
- AST and/or ALT ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2.5 times ULN
- Total bilirubin normal
- Serum creatinine ≤ 1.5 times ULN
- Able (i.e., sufficiently fluent) and willing to complete the quality of life
questionnaires in either English or French
- Fertile patients must use effective contraception
- No history of other malignancies, except adequately treated nonmelanoma skin cancer
or other curatively treated solid tumor with no evidence of disease for > 5 years
- No serious non-malignant disease resulting in a life expectancy of < 10 years
- No known hypersensitivity to any study medications
- No existing peripheral neuropathy ≥ grade 2
- No bilateral hip replacement prostheses
- No contraindication to pelvic radiotherapy including, but not limited to,
inflammatory bowel disease or severe bladder irritability
- No medical condition that would contraindicate the study treatment regimen, including
severe respiratory insufficiency, uncontrolled diabetes, or severe hypertension
- No other serious illness or psychiatric or medical condition that would preclude
management of the patient according to the study, including active uncontrolled
infection or significant cardiac dysfunction
PRIOR CONCURRENT THERAPY:
- Prior androgen suppression therapy allowed provided it was initiated no more than 4
weeks prior to study entry
- At least 4 weeks since prior 5-alpha-reductase inhibitors (e.g., finasteride) for
benign prostatic hypertrophy
- No prior cytotoxic anticancer therapy
- No prior chemotherapy for carcinoma of the prostate
- No prior surgical treatment for carcinoma of the prostate, except transurethral
resection or bilateral orchiectomy
- No prior pelvic radiotherapy
- No concurrent nilutamide
- No other concurrent investigational drugs
- No other concurrent anticancer therapy (cytotoxic therapy, biologic/immunotherapy, or
radiotherapy)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Disease-free survival
Safety Issue:
No
Principal Investigator
Michael R. McKenzie, MD, FRCPC
Investigator Role:
Study Chair
Investigator Affiliation:
British Columbia Cancer Agency
Authority:
Canada: Health Canada
Study ID:
PR12
NCT ID:
NCT00651326
Start Date:
March 2008
Completion Date:
January 2011
Related Keywords:
- Prostate Cancer
- adenocarcinoma of the prostate
- stage I prostate cancer
- stage II prostate cancer
- stage III prostate cancer
- stage IV prostate cancer
- Adenocarcinoma
- Prostatic Neoplasms
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