Prostate, Unfavorable Intermediate or Favorable High Risk (RTOG 0924)
Androgen Deprivation Therapy and High Dose Radiotherapy With or Without Whole-Pelvic Radiotherapy in Unfavorable Intermediate or Favorable High-Risk Prostate Cancer: A Phase III Randomized Trial
This randomized phase III trial studies androgen-deprivation therapy and radiation therapy in treating patients with prostate cancer. Androgens can cause the growth of prostate cancer cells. Androgen deprivation therapy may stop the adrenal glands from making androgens. Radiation therapy uses high-energy x-rays to kill tumor cells. Study Arms: 1) Active Comparator: Arm I (IMRT, 3D-CRT) Patients undergo high-dose radiotherapy of the prostate and seminal vesicles using IMRT* or 3D-CRT* QD, 5 days a week, for approximately 9 weeks. Patients may also undergo PPI brachytherapy or high-dose rate brachytherapy (I 125 or PD 103 may be used as the radioisotope). 2) Experimental: Arm II (WPRT) Patients undergo WPRT* (3D-CRT or IMRT) QD, 5 days a week, for approximately 9 weeks. Patients may also undergo brachytherapy as in Arm I.
Key Inclusion Criteria
For a patient to be eligible for participation in this study, all of the following criteria must apply.
- Pathologically (histologically or cytologically) proven diagnosis of prostatic adenocarcinoma within 180 days of registration at moderate- to high-risk for recurrence as determined by one of the following combinations: -Gleason score 7-10 + T1c-T2b (palpation) + prostate-specific antigen (PSA) < 50 ng/mL (includes intermediate- and high-risk patients); -Gleason score 6 + T2c-T4 (palpation) + PSA < 50 ng/mL OR Gleason score 6 + >= 50% (positive) biopsies + PSA < 50 ng/ml; -Gleason score 6 + T1c-T2b (palpation) + PSA > 20 ng/mL; -Patients previously diagnosed with low risk prostate cancer undergoing active surveillance who are re-biopsied and found to have unfavorable intermediate risk disease or favorable high risk disease according to the protocol criteria are eligible for enrollment within 180 days of the repeat biopsy procedure.
- History/physical examination (to include at a minimum digital rectal examination of the prostate and examination of the skeletal system and abdomen) within 90 days prior to registration.
- Clinically negative lymph nodes as established by imaging (pelvic and/or abdominal computed tomography [CT] or magnetic resonance [MR]), (but not by nodal sampling, or dissection) within 90 days prior to registration: -Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are =< 1.5 cm.
- No evidence of bone metastases (M0) on bone scan within 120 days prior to registration (sodium fluoride [NaF] positron emission tomography [PET]/CT is an acceptable substitute): -Equivocal bone scan findings are allowed if plain films (or CT or magnetic resonance imaging [MRI]) are negative for metastasis.
- Baseline serum PSA value performed with a Food and Drug Administration (FDA)-approved assay (e.g., Abbott, Hybritech) within 120 days prior to registration.
- Study entry PSA should not be obtained during the following time frames: -10-day period following prostate biopsy; -Following initiation of hormonal therapy; -Within 30 days after discontinuation of finasteride; -Within 90 days after discontinuation of dutasteride.
- Zubrod performance status 0-1 (unless otherwise specified).
- Absolute neutrophil count (ANC) >= 1,500/mm³.
- Platelets >= 100,000/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.
Key Exclusion Criteria
A patient will not be eligible for participation in this study if any of the following criteria apply.
- Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for a minimum of 3 years (1095 days) not in the pelvis (for example, carcinoma in situ of the oral cavity is permissible; however, patients with prior history of bladder cancer are not allowed); prior hematological (e.g., leukemia, lymphoma, myeloma) malignancy not allowed.
- Previous radical surgery (prostatectomy) or cryosurgery for prostate cancer.
- Previous pelvic irradiation, prostate brachytherapy, or bilateral orchiectomy.
- Previous hormonal therapy, such as LHRH agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate), estrogens (e.g., diethylstilbestrol [DES]), or surgical castration (orchiectomy).
- Prior pharmacologic androgen ablation for prostate cancer is allowed only if the onset of androgen ablation (both LHRH agonist and oral anti-androgen) is =< 45 days prior to the date of registration.
- Use of finasteride within 30 days prior to registration.
- Use of dutasteride or dutasteride/tamsulosin (Jalyn) within 90 days prior to registration.
- Previous or concurrent cytotoxic chemotherapy for prostate cancer; note that prior chemotherapy for a different cancer is allowable.
- Prior radiotherapy, including brachytherapy, to the region of the study cancer that would result in overlap of radiation therapy fields.
- 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 at the time of registration; -Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects or severe liver dysfunction; -Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immunocompromised patients.
- Patients who are sexually active and not willing/able to use medically acceptable forms of contraception.
- Prior allergic reaction to the hormones involved in this protocol.
- Patients status post a negative lymph node dissection are not eligible.
To learn more, visit ClinicalTrials.Gov
Patricia Griffin, MD
Radiation Therapy Oncology Group