Clinical trial NCT00288080
Conditions: Prostate Cancer
Keywords: stage III prostate cancer stage IIB prostate cancer stage IIA prostate cancer stage IV prostate cancer
Sponsor: Radiation Therapy Oncology Group
Start date: 2005-12-01; Completion date: 2022-05-20
Enrollment: 612 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Androgens can cause the growth of prostate cancer cells. Hormone therapy using drugs, such as leuprolide, goserelin, flutamide, or bicalutamide, may fight prostate cancer by lowering the amount of androgens the body makes. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel and prednisone, 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 hormone therapy and radiation therapy together with chemotherapy is more effective than giving hormone therapy together with radiation therapy in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying hormone therapy and radiation therapy followed by docetaxel and prednisone to see how well it works compared to hormone therapy and radiation therapy in treating patients with localized prostate cancer.

Detailed description:
OBJECTIVES:

Primary

* Compare the relative efficacy, in terms of overall survival, of the combination of androgen suppression and radiotherapy versus androgen suppression and radiotherapy followed by docetaxel and prednisone in patients with localized, high-risk prostate cancer.

Secondary

* Compare the disease-free survival and incidence of adverse events in patients treated with these regimens.
* Compare the biochemical control, local control, and freedom from distant metastases in patients treated with these regimens.
* Determine the validity of prostate-specific antigen (PSA)-defined endpoints as a surrogate for overall survival of patients treated with these regimens.
* Compare the time interval between biochemical failure and distant metastases with respect to testosterone level in patients treated with these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to risk group.

* Arm I: Patients receive androgen suppression therapy comprising luteinizing hormone-releasing hormone (LHRH) agonist (e.g., leuprolide acetate, goserelin, buserelin, or triptorelin) and oral antiandrogen (i.e., oral flutamide 3 times daily for 2 months or oral bicalutamide once daily for 2 months). Beginning at week 8, patients undergo radiotherapy 5 days a week for approximately 8 weeks. Antiandrogen therapy is discontinued at completion of radiotherapy, but LHRH agonist therapy continues for 20 months.
* Arm II: Patients receive androgen suppression therapy and undergo radiotherapy as in arm I. Beginning 4 weeks after completion of radiotherapy, patients receive docetaxel IV over 1 hour on day 1 and oral prednisone daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients continue LHRH agonist therapy as in arm I.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study.

Arms: arm 1: Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of radiation therapy (RT). arm 2: Androgen suppression (AS; LHRH agonist and oral antiandrogen) for 8 weeks followed by radiation therapy and concurrent AS. LHRH continues for 24 months after initiation of any treatment, oral antiandrogen discontinues at the end of RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression.
Interventions: intervention 1: Dexamethasone intervention 2: Prednisone intervention 3: docetaxel intervention 4: Oral antiandrogen intervention 5: Radiation therapy intervention 6: LHRH agonist
Intervention descriptions: intervention 1: Premedication of dexamethasone prior to docetaxel, per institutional standards. intervention 2: 10 mg orally per day until day 21 of the last cycle of docetaxel, beginning 28 days after the completion of RT. intervention 3: 75 mg/m2 i.v. over 1 hour (on day 1 of each cycle) every 21 days for 6 cycles, beginning 28 days after the completion of RT. intervention 4: Oral antiandrogen of treating institution's choice to be given per package instructions for 8 weeks, then concurrent with radiation therapy. Treatment is discontinued at the end of radiation therapy. intervention 5: 46.8 Gy, using either three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT), will be given to the regional lymphatics followed by a 25.2-28.8 Gy boost to the prostate, to bring the total dose to the prostate to 72.0-75.6 Gy. Daily prescription doses will be 1.8 Gy per day, 5 days per week x 8-8.5 weeks, beginning 8 weeks after the initiation of androgen suppression. intervention 6: LHRH agonist of treating institution's choice to be given per package instructions for 8 weeks, then concurrent with radiation therapy, and then until 24 months from initiation of any treatment has been reached.

Protocol documents: