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

NCT ID: NCT00651326

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-02
• Study Completion Date: 2011-01-18

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.

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Antiandrogen; LHRH; Docetaxel, Radiation Therapy

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

Group Type: ACTIVE_COMPARATOR

bicalutamide

Intervention Type: DRUG

buserelin

Intervention Type: DRUG

flutamide

Intervention Type: DRUG

goserelin

Intervention Type: DRUG

leuprolide acetate

Intervention Type: DRUG

neoadjuvant therapy

Intervention Type: PROCEDURE

quality-of-life assessment

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

46 Gy in 23 fractions over < 5 weeks.

Boost:

24-28 Gy in 12-14 fractions over < 3 weeks

Docetaxel

Intervention Type: DRUG

Antiandrogen; LHRH; Radiation Therapy

Antiandrogen (Flutamide or Bicalutamide) LHRH agonist (Eligard)

Group Type: ACTIVE_COMPARATOR

bicalutamide

Intervention Type: DRUG

buserelin

Intervention Type: DRUG

flutamide

Intervention Type: DRUG

goserelin

Intervention Type: DRUG

leuprolide acetate

Intervention Type: DRUG

neoadjuvant therapy

Intervention Type: PROCEDURE

quality-of-life assessment

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

46 Gy in 23 fractions over < 5 weeks.

Boost:

24-28 Gy in 12-14 fractions over < 3 weeks

Interventions

bicalutamide

Intervention Type: DRUG

buserelin

Intervention Type: DRUG

flutamide

Intervention Type: DRUG

goserelin

Intervention Type: DRUG

leuprolide acetate

Intervention Type: DRUG

neoadjuvant therapy

Intervention Type: PROCEDURE

quality-of-life assessment

Intervention Type: PROCEDURE

radiation therapy

46 Gy in 23 fractions over < 5 weeks.

Boost:

24-28 Gy in 12-14 fractions over < 3 weeks

Intervention Type: RADIATION

Docetaxel

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael R. McKenzie, MD, FRCPC

Role: STUDY_CHAIR

British Columbia Cancer Agency

Kim N. Chi, MD

Role: STUDY_CHAIR

British Columbia Cancer Agency

Locations

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, , Canada

Countries

Canada

Other Identifiers

CAN-NCIC-PR12

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000589247

Identifier Type: OTHER

Identifier Source: secondary_id

PR12

Identifier Type: -

Identifier Source: org_study_id