Androgen Suppression and Radiation With/Out Docetaxel in High-Risk Localized Prostate Cancer

Prostate Cancer Clinical Trial

— DART  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00651326
• Other study ID #: PR12
• Secondary ID: CAN-NCIC-PR12CDR
• Status: Terminated
• Phase: Phase 3
• Start date: June 2, 2008
• Est. completion date: January 18, 2011

Study information

• Verified date: March 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as flutamide, bicalutamide, leuprolide, buserelin, and goserelin, may lessen the amount of androgens made by the body. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving androgen suppression therapy together with radiation therapy is more effective with or without docetaxel in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying androgen suppression therapy, radiation therapy, and docetaxel to see how well they work compared with androgen suppression therapy and radiation therapy in treating patients with high-risk localized prostate cancer.

CLOSURE: This trial closed to further accrual in November 2009. The study endpoints will not be reached.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 48
• Est. completion date: January 18, 2011
• Est. primary completion date: May 14, 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• bicalutamide

• buserelin

• flutamide

• goserelin

• leuprolide acetate

Procedure:
• neoadjuvant therapy

• quality-of-life assessment

Radiation:
• radiation therapy
46 Gy in 23 fractions over < 5 weeks. Boost: 24-28 Gy in 12-14 fractions over < 3 weeks

Drug:
• Docetaxel

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary
Canada	Cross Cancer Institute	Edmonton
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna
Canada	London Regional Cancer Program	London
Canada	Credit Valley Hospital	Mississauga
Canada	McGill University - Dept. Oncology	Montreal
Canada	Lakeridge Health Oshawa	Oshawa
Canada	Ottawa Health Research Institute - General Division	Ottawa
Canada	Saskatoon Cancer Centre	Saskatoon
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto
Canada	BCCA - Vancouver Cancer Centre	Vancouver
Canada	CancerCare Manitoba	Winnipeg

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival
Secondary	Overall survival
Secondary	Time to biochemical disease progression
Secondary	Time to local disease progression
Secondary	Time to distant disease progression
Secondary	Time to next anti-cancer therapy
Secondary	Progression-free survival
Secondary	Degree of prostate-specific antigen (PSA) suppression prior to radiotherapy
Secondary	Quality of life
Secondary	Adverse events