Clinical TrialsThe James Cancer Center Columbus, OH
open for enrollment
Androgen-Deprivation Therapy and Radiation Therapy in Treating Patients with Prostate Cancer
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.
I. Demonstrate that prophylactic, neoadjuvant, androgen-deprivation therapy (NADT) and whole-pelvic radiation therapy (WPRT) will result in improvement in overall survival (OS) of patients with “unfavorable” intermediate-risk or “favorable” high-risk prostate cancer compared to NADT and high-dose prostate and seminal vesicle (SV) radiation therapy (prostate [P] + SV radiation therapy [RT]) using intensity-modulated radiotherapy (IMRT) or external-beam RT (EBRT) with a high-dose rate (HDR) or a permanent prostate (radioactive seed) implant (PPI) boost.
I. Demonstrate that prophylactic WPRT improves biochemical control.
II. Distant metastasis (DM)-free survival.
III. Cause-specific survival (CSS).
IV. Compare acute and late treatment-adverse events between patients receiving NADT and WPRT versus NADT + P and SV RT.
V. Determine whether health-related quality of life (HRQOL), as measured by the Expanded Prostate Cancer Index Composite (EPIC), significantly worsens with increasing aggressiveness of treatment (i.e., Arm 2, NADT + WPRT). (closed to patient accrual 3/9/15)
VI. Determine whether more aggressive treatment (Arm 2, NADT + WPRT) is associated with a greater increase in fatigue (Patient-Reported Outcome Measurement Information System [PROMIS] Fatigue Short Form) from baseline to last week of treatment, and a greater increase in circulating inflammatory markers (interleukin [IL]-1, IL-1 receptor antagonist [ra], IL-6, tumor necrosis factor [TNF]-alpha, and C-reactive protein). (closed to patient accrual 3/9/15)
VII. Demonstrate an incremental gain in OS and CSS with more aggressive therapy that outweighs any detriments in the primary generic domains of HRQOL (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). (closed to patient accrual 3/9/15)
VIII. Determine whether changes in fatigue from baseline to the next three time points (week prior to RT, last week of treatment, and 3 months after treatment) are associated with changes in circulating cytokines, mood, sleep, and daily activities across the same time points.
IX. Collect paraffin-embedded tissue blocks, plasma, whole blood, and urine for planned and future translational research analyses.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
All patients receive neoadjuvant androgen-deprivation therapy comprising bicalutamide orally (PO) once daily (QD) or flutamide PO thrice daily (TID) for 6 months, and luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy comprising leuprolide acetate, goserelin acetate, buserelin, triptorelin, or degarelix subcutaneously (SC) or intramuscularly (IM) every 1 to 3 months beginning 2 months prior to radiotherapy and continuing for 6 or 32 months. Radiotherapy begins within 8-10 weeks after beginning LHRH agonist/antagonist injection.
ARM I: Patients undergo high-dose radiotherapy of the prostate and seminal vesicles using IMRT* or 3D-conformal radiation therapy (3D-CRT)* QD, 5 days a week, for approximately 9 weeks. Patients may also undergo PPI brachytherapy or high-dose rate brachytherapy (iodine I 125 or palladium Pd 103 may be used as the radioisotope).
ARM II: 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.
NOTE: * Patients undergoing brachytherapy implant receive 5 weeks of IMRT, 3D-CRT, or WPRT.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 3 years, and then yearly thereafter.
Are you eligible?
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
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 immuno-compromised 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