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

Sponsor:	NCIC Clinical Trials Group
Information provided by:	NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00651326

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 III

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:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Flutamide Gonadorelin Gonadorelin hydrochloride Leuprolide Buserelin Goserelin Buserelin acetate Leuprolide acetate Bicalutamide Docetaxel LH-RH

U.S. FDA Resources

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
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

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

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

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Ralph Meyer M.D., 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:	January 18, 2011
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:

Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Androgen Antagonists
Flutamide
Bicalutamide
Androgens

Buserelin
Leuprolide
Goserelin
Docetaxel
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Hormones
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 13, 2012