Androgen Suppression Therapy and Radiation Therapy With or Without Docetaxel in Treating Patients With High-Risk Localized Prostate Cancer

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00651326
First received: April 1, 2008
Last updated: December 17, 2012
Last verified: December 2012
  Purpose

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 Intervention Phase
Prostate Cancer
Drug: bicalutamide
Drug: buserelin
Drug: flutamide
Drug: goserelin
Drug: leuprolide acetate
Procedure: neoadjuvant therapy
Procedure: quality-of-life assessment
Radiation: radiation therapy
Drug: Docetaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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 (DART)

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Time to biochemical disease progression [ Designated as safety issue: No ]
  • Time to local disease progression [ Designated as safety issue: No ]
  • Time to distant disease progression [ Designated as safety issue: No ]
  • Time to next anti-cancer therapy [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Degree of prostate-specific antigen (PSA) suppression prior to radiotherapy [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]
  • Adverse events [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: March 2008
Study Completion Date: January 2011
Arms Assigned Interventions
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


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00651326

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

No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00651326     History of Changes
Other Study ID Numbers: PR12, CAN-NCIC-PR12, CDR0000589247
Study First Received: April 1, 2008
Last Updated: December 17, 2012
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
adenocarcinoma of the prostate
stage I prostate cancer
stage II prostate cancer
stage III prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Androgen Antagonists
Androgens
Bicalutamide
Docetaxel
Flutamide
Leuprolide
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Fertility Agents
Fertility Agents, Female
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 22, 2014