Hormone Therapy and Radiation Therapy or Hormone Therapy and Radiation Therapy Followed by Docetaxel and Prednisone in Treating Patients With Localized Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Drug: Oral antiandrogenRadiation: Radiation therapyDrug: LHRH agonist
- Registration Number
- NCT00288080
- Lead Sponsor
- Radiation Therapy Oncology Group
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 612
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Androgen suppression + Radiation Therapy LHRH agonist 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). Androgen suppression + Radiation Therapy + Chemotherapy LHRH agonist 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. Androgen suppression + Radiation Therapy Oral antiandrogen 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). Androgen suppression + Radiation Therapy 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). Androgen suppression + Radiation Therapy + Chemotherapy Oral antiandrogen 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. Androgen suppression + Radiation Therapy + Chemotherapy 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 RT. Following completion of RT, 6 cycles of docetaxel (premedicated with dexamethasone) and prednisone are delivered concurrently with androgen suppression. Androgen suppression + Radiation Therapy + Chemotherapy Dexamethasone 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. Androgen suppression + Radiation Therapy + Chemotherapy Prednisone 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. Androgen suppression + Radiation Therapy + Chemotherapy docetaxel 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.
- Primary Outcome Measures
Name Time Method Overall Survival 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 Outcome Measures
Name Time Method Incidence of Adverse Events From start of treatment until the end of follow-up Adverse events are graded using CTCAE v3.0. The worst grade of all adverse events for each patient is counted.
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. Prentice's operational criteria for determining whether determining whether biochemical failure (surrogate endpoint) is a suitable endpoint for overall survival (true endpoint):
1. Treatment is prognostic for true endpoint
2. Treatment is prognostic for surrogate endpoint
3. Surrogate is prognostic for true endpoint
4. The full effect of the treatment on the true endpoint is explained by the surrogate.
If any of the criteria are not met, it is concluded that biochemical failure is not a suitable surrogate for overall survival. Therefore, if any of the criteria are met, the other criteria do not do not need to be evaluated.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. A failure for disease-free survival is the first of the following: biochemical failure, local failure, distant metastases, or death due to any cause. The corresponding outcome time was measured from the date of randomization. Disease-free survival rates at 4 years were calculated using the Kaplan-Meier method.
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. Biochemical failure is defined as the first of either prostate-specific antigen (PSA) failure or the initiation of salvage hormone therapy. PSA failure is defined as a rise in PSA of 2 ng/ml over the nadir PSA. Distant failure is defined as the first occurrence of distant metastasis.
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. Distant failure was considered when there was evidence of metastatic disease. Patients who experienced death without distant failure, local failure prior to distant failure, and biochemical failure prior to distant failure were censored on the date of the competing event. The corresponding outcome time was measured from the date of randomization. Distant failure rates at 4 year were calculated using the Kaplan-Meier method.
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. Four-year rates are shown (Kaplan-Meier estimates). Biochemical control is defined as freedom from biochemical failure. Biochemical failure was considered as the first of either prostate-specific antigen (PSA) failure or initiation of salvage hormone therapy. PSA failure was defined as a rise of 2 ng/ml over the nadir PSA. Patients who experienced death without biochemical failure, local failure prior to biochemical failure, or development of distant metastases prior to biochemical failure were censored on the date of the competing event. The corresponding outcome time was measured from the date of randomization.
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. Local control is defined as the absence of local failure which is the first of either progression or recurrence within the prostate. Progression of the tumor was considered to have occurred when there was a 25% or greater increase in the product of the two largest perpendicular diameters of the prostate. Recurrence was defined as the reappearance of disease after a complete response. Patients who experienced death without local failure, biochemical failure prior to local failure, and development of distant metastases prior to local failure were censored on the date of the competing event. The corresponding outcome time was measured from the date of randomization. Due to an insufficient number of events (2 in each arm), this endpoint was not statistically compared. Local control rates at 4 years were calculated using the Kaplan-Meier method.
Trial Locations
- Locations (254)
UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Providence Cancer Center
🇺🇸Anchorage, Alaska, United States
Arizona Oncology Services Foundation
🇺🇸Phoenix, Arizona, United States
Arizona Oncology - Tucson
🇺🇸Tucson, Arizona, United States
Auburn Radiation Oncology
🇺🇸Auburn, California, United States
Providence Saint Joseph Medical Center - Burbank
🇺🇸Burbank, California, United States
Radiation Oncology Centers - Cameron Park
🇺🇸Cameron Park, California, United States
Mercy Cancer Center at Mercy San Juan Medical Center
🇺🇸Carmichael, California, United States
Enloe Cancer Center at Enloe Medical Center
🇺🇸Chico, California, United States
Cancer Care Center at John Muir Health - Concord Campus
🇺🇸Concord, California, United States
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