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

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

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: leuprolide acetate; Procedure: neoadjuvant therapy; Procedure: quality-of-life assessment; Drug: buserelin; Drug: flutamide; Drug: bicalutamide; Drug: goserelin; Radiation: radiation therapy

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada, T2N 4N2
    • Tom Baker Cancer Centre
  • Edmonton, Canada, T6G 1Z2
    • Cross Cancer Institute
  • Hamilton, Canada, L8V 5C2
    • Juravinski Cancer Centre at Hamilton Health Sciences
  • Kelowna, Canada, V1Y 5L3
    • BCCA - Cancer Centre for the Southern Interior
  • London, Canada, N6A 4L6
    • London Regional Cancer Program
  • Mississauga, Canada, L5M 2N1
    • Credit Valley Hospital
  • Montreal, Canada, H2W 1S6
    • McGill University - Dept. Oncology
  • Oshawa, Canada, L1G 2B9
    • Lakeridge Health Oshawa
  • Ottawa, Canada, K1H 8L6
    • Ottawa Health Research Institute - General Division
  • Saskatoon, Canada, S7N 4H4
    • Saskatoon Cancer Centre
  • Toronto, Canada, M5G 2M9
    • Univ. Health Network-Princess Margaret Hospital
  • Vancouver, Canada, V5Z 4E6
    • BCCA - Vancouver Cancer Centre
  • Winnipeg, Canada, R3E 0V9
    • CancerCare Manitoba

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Antiandrogen; LHRH; Docetaxel, Radiation Therapy; Antiandrogen (Flutamide or Bicalutamide) LHRH agonist (Eligard) Docetaxel	Drug: Docetaxel; Drug: leuprolide acetate; Procedure: neoadjuvant therapy; Procedure: quality-of-life assessment; Drug: buserelin; Drug: flutamide; Drug: bicalutamide; Drug: goserelin; Radiation: radiation therapy; 46 Gy in 23 fractions over < 5 weeks. Boost: 24-28 Gy in 12-14 fractions over < 3 weeks
Active Comparator: Antiandrogen; LHRH; Radiation Therapy; Antiandrogen (Flutamide or Bicalutamide) LHRH agonist (Eligard)	Drug: leuprolide acetate; Procedure: neoadjuvant therapy; Procedure: quality-of-life assessment; Drug: buserelin; Drug: flutamide; Drug: bicalutamide; Drug: goserelin; Radiation: radiation therapy; 46 Gy in 23 fractions over < 5 weeks. Boost: 24-28 Gy in 12-14 fractions over < 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Disease-free survival

Secondary Outcome Measures

Outcome Measure
Adverse events
Progression-free survival
Overall survival
Quality of life
Time to biochemical disease progression
Time to local disease progression
Time to distant disease progression
Time to next anti-cancer therapy
Degree of prostate-specific antigen (PSA) suppression prior to radiotherapy

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Investigators: Study Chair: Kim N. Chi, MD, British Columbia Cancer Agency; Study Chair: Michael R. McKenzie, MD, FRCPC, British Columbia Cancer Agency

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2008
• Primary Completion (Actual): May 14, 2010
• Study Completion (Actual): January 18, 2011

Study Registration Dates

• First Submitted: April 1, 2008
• First Submitted That Met QC Criteria: April 1, 2008
• First Posted (Estimated): April 2, 2008

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: stage III prostate cancer; stage IV prostate cancer; adenocarcinoma of the prostate; stage I prostate cancer; stage II prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Androgen Antagonists; Docetaxel; Leuprolide; Goserelin; Bicalutamide; Flutamide; Buserelin
• Other Study ID Numbers: PR12; CAN-NCIC-PR12 (Registry Identifier: PDQ); CDR0000589247 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No