Radiation Therapy With or Without Androgen-Deprivation Therapy in Treating Patients With Prostate Cancer | NCT00936390 | Trialant

Radiation Therapy With or Without Androgen-Deprivation Therapy in Treating Patients With Prostate Cancer | NCT00936390 | Trialant

Official Title: A Phase III Prospective Randomized Trial of Dose-Escalated Radiotherapy With or Without Short-Term Androgen Deprivation Therapy for Patients With Intermediate-Risk Prostate Cancer
Brief 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.
Detailed Description: 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. After completion of study therapy, patients are followed up periodically.

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: Male
Accepts Healthy Volunteers: No
Eligibility Criteria: Inclusion Criteria:

Pathologically (histologically) proven diagnosis of prostatic adenocarcinoma, at intermediate risk for recurrence, within 180 days prior to registration as determined by having one or more of the following intermediate-risk features: Gleason score 7; prostate-specific antigen (PSA) >10 but ≤20; clinical stage T2b-T2c.

Patients previously diagnosed with low risk (Gleason score ≤ 6, clinical stage < T2a, and PSA < 10) 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 180 days of the repeat biopsy procedure.

Clinically negative lymph nodes as established by imaging (pelvic +/- abdominal CT or MRI), nodal sampling, or dissection within 60 days prior to registration, except as noted immediately below:

Patients with a single intermediate risk factor only do not require abdominopelvic imaging, but these studies may be obtained at the discretion of the treating physician. Patients with 2 or 3 risk factors are required to undergo pelvic +/- abdominal CT or MRI.

Patients with lymph nodes equivocal or questionable by imaging are eligible without biopsy if the nodes are ≤1.5 cm; any node larger than this on imaging will require negative biopsy for eligibility.

No evidence of bone metastases (M0) on bone scan within 60 days prior to registration.

Bone scan is not required for patients enrolled with a single intermediate risk factor only, but this scan may be obtained at the discretion of the treating physician. Patients with 2 or 3 risk factors will require a negative bone scan for eligibility.

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

History/physical examination (to include, at a minimum, digital rectal examination of the prostate and examination of the skeletal system and abdomen, and formal comorbidity assessment via the ACE-27 instrument) within 60 days prior to registration.

Zubrod Performance Status 0-1

Age ≥ 18

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

Study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of ADT; (3) within 30 days after discontinuation of finasteride; or (4) within 90 days after discontinuation of dutasteride.

For patients undergoing brachytherapy only: complete blood count (CBC)/differential obtained within 60 days prior to registration, with adequate bone marrow function defined as follows:

Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3

Platelets ≥ 100,000 cells/mm3

Hemoglobin (Hgb) ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)

Patient must be able to provide study-specific informed consent prior to study entry.

Exclusion Criteria:

Patients with Gleason Score ≥ 8; PSA > 20; OR Clinical Stage ≥ T3 are ineligible for this trial.

Should findings of extracapsular extension or seminal vesicle invasion be 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.

Patients with all three intermediate risk factors who also have ≥ 50% of the number of their biopsy cores positive for cancer are ineligible for this trial.

Prior invasive malignancy (except non-melanomatous skin cancer) or hematological (e.g., leukemia, lymphoma, myeloma) malignancy unless disease free for a minimum of 5 years (prior diagnoses of carcinoma in situ are permitted)

Prior radical surgery (prostatectomy), high-intensity focused ultrasound (HIFU) or cryosurgery for prostate cancer

Prior hormonal therapy, such as LHRH agonists (e.g., goserelin, leuprolide), antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or bilateral orchiectomy

Use of finasteride within 30 days prior to registration

Use of dutasteride within 90 days prior to registration

Prior or concurrent cytotoxic chemotherapy for prostate cancer; prior chemotherapy for a different cancer is permitted.

Prior RT, including brachytherapy, to the region of the study cancer that would result in overlap of RT fields

Any patient undergoing brachytherapy must have transrectal ultrasound confirmation of prostate volume <60 cc, American Urological Association Symptom Index (AUA-SI) score ≤15 within 60 days of registration, and no history of prior transurethral resection of the prostate (TURP); prior TURP is permitted for patients who receive EBRT only)

Severe, active co-morbidity, defined as follows:

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

Transmural myocardial infarction within the last 6 months

Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration

Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.

Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. While the treatment employed in this study is not significantly immunosuppressive, it is felt that a diagnosis of AIDS associated with prostate cancer is likely to impact this study's primary endpoint of overall survival. Patients who are HIV seropositive but do not meet criteria for diagnosis of AIDS are eligible for study participation.

Men who are sexually active with a woman of child-bearing potential and not willing/able to use medically acceptable forms of contraception (e.g., surgical, barrier, medicinal) during protocol treatment and during the first 3 months after cessation of protocol treatment; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.