Clinical trial NCT00004054
Conditions: Prostate Cancer
Keywords: stage IIB prostate cancer stage IIA prostate cancer stage III prostate cancer stage IV prostate cancer
Sponsor: Radiation Therapy Oncology Group
Start date: 2000-01-01; Completion date: 2013-11-01
Enrollment: 397 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Hormones can stimulate the production of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy plus radiation therapy is more effective with or without combination chemotherapy for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy plus radiation therapy with or without combination chemotherapy in treating patients who have prostate cancer.

Detailed description:
OBJECTIVES:

* Compare the efficacy of androgen suppression and radiotherapy with or without subsequent paclitaxel, estramustine, and etoposide, in terms of overall and disease-free survival, biochemical and local control, and freedom from distant metastasis, in patients with localized high-risk prostate cancer.
* Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to prostate-specific antigen level (≤ 10 ng/mL vs 11-100 ng/mL), tumor stage (T1-2 vs T3-4), Gleason score (7 vs 8-10), and prior hormone use (yes vs no). Patients are randomized to one of two treatment arms.

All patients receive androgen suppression comprising a luteinizing hormone-releasing hormone (LHRH) agonist AND bicalutamide OR flutamide for 4 months. Beginning 8 weeks after the initiation of androgen suppression, all patients undergo radiotherapy once daily, 5 days a week, for 7-8 weeks. Patients who received prior androgen suppression therapy count time to radiotherapy from start date of prior hormonal therapy.

* Arm I: Patients continue androgen suppression therapy (LHRH agonist only) for approximately 20 more months after radiotherapy is completed.
* Arm II: Patients continue therapy as in arm I and receive chemotherapy beginning 28 days after completing radiotherapy. Chemotherapy comprises oral estramustine 3 times daily and oral etoposide twice daily on days 1-14 and paclitaxel IV over 1 hour on day 2. Chemotherapy repeats every 21 days for 4 courses.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,440 patients will be accrued for this study within 6 years.

Arms: arm 1: Androgen suppression (AS) (Luteinizing hormone releasing hormone agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT). arm 2: AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.
Interventions: intervention 1: bicalutamide intervention 2: estramustine phosphate sodium intervention 3: etoposide intervention 4: flutamide intervention 5: paclitaxel intervention 6: Luteinizing hormone releasing hormone [LHRH] agonist intervention 7: Radiation therapy intervention 8: warfarin
Intervention descriptions: intervention 1: Administered orally at a dose of one 50mg tablet per day. Begins 8 weeks prior to radiotherapy and continues throughout radiotherapy. intervention 2: 280 mg three times a day for 14 days and repeated every 3 weeks for 4 cycles intervention 3: 50 mg/m\^2 in divided doses b.i.d. for 14 days and repeated every 3 weeks for 4 cycles intervention 4: Administered orally at a dose of two 125 mg capsules three times a day for a total daily dose of 750 mg. Begins 8 weeks prior to radiotherapy and continues throughout radiotherapy. intervention 5: 135 mg/m\^2 given as a 1-hour infusion (on day 2 of each cycle) and repeated every 3 weeks for 4 cycles intervention 6: Releasing hormone agonists (such as leuprolide, goserelin, buserelin, triptorelin) will be given for 4 months intervention 7: Radiation will begin 8 weeks following the initiation of hormone administration: 46.8 Gy to the regional lymphatics followed by a 23.4 Gy boost to the prostate to bring the total dose to the prostate to 70.2 Gy. Daily tumor doses will be 1.8 Gy per day, 5 days per week x 7-8 weeks. intervention 8: To keep international normalized ratio (INR) \> 1.5 and \< 2.5; begins with the start of chemotherapy and will be given continuously until 4 weeks after the end of the fourth cycle of chemotherapy

Protocol documents: