A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT Vs AS and 3DCTR/IMRT Followed by Chemotherapy With Docetaxel and Prednisone for Localized, High-Risk, Prostate Cancer
Overview
- Phase
- Phase 3
- Intervention
- Prednisone
- Conditions
- Prostate Cancer
- Sponsor
- Radiation Therapy Oncology Group
- Enrollment
- 612
- Locations
- 254
- Primary Endpoint
- Overall Survival
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Androgen suppression + Radiation Therapy + Chemotherapy
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.
Intervention: Prednisone
Androgen suppression + Radiation Therapy
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).
Intervention: Oral antiandrogen
Androgen suppression + Radiation Therapy
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).
Intervention: Radiation therapy
Androgen suppression + Radiation Therapy
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).
Intervention: LHRH agonist
Androgen suppression + Radiation Therapy + Chemotherapy
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.
Intervention: Dexamethasone
Androgen suppression + Radiation Therapy + Chemotherapy
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.
Intervention: docetaxel
Androgen suppression + Radiation Therapy + Chemotherapy
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.
Intervention: Oral antiandrogen
Androgen suppression + Radiation Therapy + Chemotherapy
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.
Intervention: Radiation therapy
Androgen suppression + Radiation Therapy + Chemotherapy
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.
Intervention: LHRH agonist
Outcomes
Primary Outcomes
Overall Survival
Time Frame: From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.
Four-year rates are shown. Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
Secondary Outcomes
- Incidence of Adverse Events(From start of treatment until the end of follow-up)
- Validity of PSA Endpoint as a Surrogate for Overall Survival(From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.)
- Disease-free Survival(From randomization to date of progression, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.)
- The Time Interval Between Biochemical Failure and Distant Failure Respect to Testosterone Level(From date of biochemical failure to development of distant metastasis. Maximum follow-up was 12.9 years.)
- Distant Metastasis(From randomization to date of distant metastasis, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.)
- Biochemical Control(From randomization to date of biochemical failure, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.)
- Local Control(From randomization to date of local failure, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.)