Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells and shrink tumors. Androgens can cause the growth of prostate cancer cells. Androgen-deprivation therapy may lessen the amount of androgens made by the body. It is not yet known whether radiation therapy is more effective with or without androgen-deprivation therapy in treating patients with prostate cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with androgen-deprivation therapy in treating patients with prostate cancer.

Further Study Information

OBJECTIVES:

Primary

• Demonstrate an overall survival (OS) advantage in patients with intermediate-risk prostate cancer treated with dose-escalated radiotherapy (RT) with versus without short-term androgen-deprivation therapy (ADT).

Secondary

• Determine whether the addition of ADT to dose-escalated RT versus RT alone improves clinical failures, biochemical failure by the "nadir +2", freedom from failure, rate of salvage ADT, and prostate cancer-specific mortality in these patients.

• Estimate the magnitude of benefit of ADT with respect to OS in patients treated with different RT modalities (i.e., external-beam radiation therapy alone vs low-dose rate brachytherapy boost vs high-dose rate brachytherapy boost).

• Compare acute and late treatment adverse events of these regimens and correlate these events with the presence or absence of pre-existing comorbidity as documented by the Adult Comorbidity Evaluation 27 assessment.

OUTLINE: This is a multicenter, dose-escalation study of radiotherapy. Patients are stratified according to number of risk factors (1 vs 2-3), comorbidity (ACE-27 grade ≥ 2 vs < 2), and radiotherapy (RT) modality (dose-escalated external-beam RT [EBRT] vs EBRT and low-dose rate brachytherapy boost vs EBRT and high-dose rate brachytherapy boost). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo EBRT* once daily on days 1-5 for about 9 weeks (44 treatments). Some patients instead receive EBRT with high-dose rate or low-dose rate brachytherapy implant on days 1-5 for about 5 weeks (25 treatments). NOTE: *Type of RT is at discretion of treating physician and may include either 3D-conformal RT or intensity-modulated RT.

• Arm II: Patients receive androgen-deprivation therapy comprising luteinizing-hormone releasing-hormone (LHRH) agonist (leuprolide, goserelin, buserelin, or triptorelin) subcutaneously or as an injection every 1 to 3 months AND an oral antiandrogen therapy (flutamide 3 times daily or bicalutamide once daily) for 6 months. Beginning 8 weeks after the first LHRH injection, patients undergo radiotherapy as in arm I.

After completion of study therapy, patients are followed up periodically.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate diagnosed within the past 180 days and at intermediate-risk for recurrence by meeting ≥ 1 of the following criteria:

• Gleason score > 7

• PSA > 10 and ≤ 20 ng/mL

• Baseline serum PSA value performed within 60 days with an FDA-approved assay (e.g., Abbott, Hybritech)

• Baseline PSA must not be obtained during any of the following time frames:10-day period after prostate biopsy, after initiation of androgen-deprivation therapy, or within the past 30 days after discontinuation of finasteride (90 days for dutasteride)

• Clinical stage T2b or T2c disease

• Patients previously diagnosed with low-risk (Gleason score < 6, clinical stage < T2a, and PSA < 10 ng/mL) prostate cancer undergoing active surveillance who are re-biopsied and found to have intermediate-risk disease according to the protocol criteria are eligible for enrollment within 6 months of the repeat biopsy procedure

• Patients with Gleason Score ≥ 8, PSA > 20 ng/mL, OR clinical stage ≥ T3 are ineligible for this trial

• If findings of extracapsular extension or seminal vesicle invasion are noted on prostate MRI, this study, if used, will not render patients ineligible for accrual to this protocol

• Primary tumor staging for eligibility purposes is to be based on palpable or core biopsy evidence only with respect to extracapsular extension or seminal vesicle involvement

• No patients with all 3 intermediate-risk factors who also have ≥ 50% of the number of their biopsy cores positive for cancer

• The percentage of biopsy cores involved will only be considered with respect to eligibility for those patients with all 3 of the above risk factors (i.e., patients with one or two of the above risk factors are eligible irrespective of the percentage of biopsy cores involved)

• Clinically negative lymph nodes as established by imaging (pelvic and/or abdominal CT scan or MRI), nodal sampling, or dissection within the past 60 days (required for patients with 2-3 risk factors)

• Abdominal imaging not required for a single intermediate-risk factor (these studies may be obtained at the discretion of the treating physician)

• Lymph nodes that are equivocal or questionable by imaging allowed without biopsy if nodes ≤ 1.5 cm

• Any node > 1.5 cm on imaging requires a negative biopsy

• No evidence of bone metastases on bone scan within the past 60 days

• Bone scan not required for patients with a single intermediate-risk factor (scan may be obtained at the discretion of the treating physician)

• Equivocal bone scan findings allowed if plain film x-rays negative for metastasis

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1

• ANC ≥ 1,800/mm^3*

• Platelet count ≥ 100,000/mm^3*

• Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve level allowed)*

• NOTE: *For patients undergoing brachytherapy only.

• Fertile patients must use effective contraception during and for the 3 months after cessation of protocol treatment

• No invasive malignancy or hematological malignancy (e.g., leukemia, lymphoma, myeloma) within the past 5 years except adequately treated non-melanomatous skin cancer

• Prior diagnoses of carcinoma in situ allowed

• No severe or active co-morbidity with any of the following:

• Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months

• Transmural myocardial infarction within the past 6 months

• Acute bacterial or fungal infection requiring intravenous antibiotics

• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy, within the past 30 days

• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

• Laboratory tests for liver function and coagulation parameters not required for entry into this protocol

• AIDS based upon current CDC definition

• HIV testing not required for entry into this protocol

• HIV-seropositive patients who do not meet criteria for diagnosis of AIDS allowed

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior radical surgery (prostatectomy), high-intensity focused ultrasound, or cryosurgery for prostate cancer

• No prior hormonal therapy, such as LHRH agonists (e.g., goserelin, leuprolide), antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or bilateral orchiectomy

• No finasteride within past 30 days (90 days for dutasteride)

• No prior or concurrent cytotoxic chemotherapy for prostate cancer

• Prior chemotherapy for a different cancer allowed

• No prior radiotherapy (RT), including brachytherapy, to the region of the study cancer that would result in overlap of RT fields

• Patients undergoing brachytherapy must have transrectal ultrasound confirmation of prostate volume < 60 cc, AUA score ≤ 15 within the past 60 days of registration, and no history of prior transurethral resection of the prostate (TURP)

• TURP allowed for patients who receive external-beam radiation therapy only

Trial Contact Information

Trial Lead Organizations/Sponsors

Radiation Therapy Oncology Group

Alvaro A. Martinez

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00936390
Information obtained from ClinicalTrials.gov on November 20, 2012

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