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

Sponsor
NCIC Clinical Trials Group (Other)
Overall Status
Terminated
CT.gov ID
NCT00651326
Collaborator
(none)
48
13
2
34.5
3.7
0.1

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
48 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 3, 2008
Actual Primary Completion Date :
May 14, 2010
Actual Study Completion Date :
Jan 18, 2011

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Antiandrogen; LHRH; Docetaxel, Radiation Therapy

Antiandrogen (Flutamide or Bicalutamide) LHRH agonist (Eligard) Docetaxel

Drug: bicalutamide

Drug: buserelin

Drug: flutamide

Drug: goserelin

Drug: leuprolide acetate

Procedure: neoadjuvant therapy

Procedure: 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

Active Comparator: Antiandrogen; LHRH; Radiation Therapy

Antiandrogen (Flutamide or Bicalutamide) LHRH agonist (Eligard)

Drug: bicalutamide

Drug: buserelin

Drug: flutamide

Drug: goserelin

Drug: leuprolide acetate

Procedure: neoadjuvant therapy

Procedure: 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

Outcome Measures

Primary Outcome Measures

  1. Disease-free survival []

Secondary Outcome Measures

  1. Overall survival []

  2. Time to biochemical disease progression []

  3. Time to local disease progression []

  4. Time to distant disease progression []

  5. Time to next anti-cancer therapy []

  6. Progression-free survival []

  7. Degree of prostate-specific antigen (PSA) suppression prior to radiotherapy []

  8. Quality of life []

  9. Adverse events []

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
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)

Contacts and Locations

Locations

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

Sponsors and Collaborators

  • NCIC Clinical Trials Group

Investigators

  • Study Chair: Michael R. McKenzie, MD, FRCPC, British Columbia Cancer Agency
  • Study Chair: Kim N. Chi, MD, British Columbia Cancer Agency

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00651326
Other Study ID Numbers:
  • PR12
  • CAN-NCIC-PR12
  • CDR0000589247
First Posted:
Apr 2, 2008
Last Update Posted:
Apr 2, 2020
Last Verified:
Mar 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by NCIC Clinical Trials Group
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 2, 2020