A Randomized Phase III Trial of Hypofractionated Post-Prostatectomy Radiation Therapy (HYPORT) Versus Conventional Post-Prostatectomy Radiation Therapy (COPORT)
A Randomized Phase III Trial of Hypofractionated Post-Prostatectomy Radiation Therapy (HYPORT) Versus Conventional Post-Prostatectomy Radiation Therapy (COPORT)
This randomized phase III trial studies how well hypofractionated radiation therapy works compared to conventional radiation therapy after surgery in treating patients with prostate cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Conventional radiation therapy uses high energy x-rays, gamma rays, neutrons, protons, or other sources to kill tumor cells and shrink tumors. It is not yet known whether giving hypofractionated radiation therapy or conventional radiation therapy after surgery may work better in treating patients with prostate cancer.
PRIMARY OBJECTIVES:
I. To demonstrate that hypofractionated post-prostatectomy radiotherapy (HYPORT) does not increase patient-reported gastrointestinal (GI) or genitourinary (GU) symptoms over conventionally fractionated post-prostatectomy (COPORT) at the 2-year time point.
SECONDARY OBJECTIVES:
I. To compare patient-reported GI symptoms using the Expanded Prostate Cancer Index Composite (EPIC)-26 at end of radiation therapy (RT) and 6, 12, 24, and 60 months from end of treatment.
II. To compare patient-reported GU symptoms using the EPIC-26 at end of RT and 6, 12, 24, and 60 months from end of treatment.
III. To compare time to progression (TTP) where progression is defined as the first occurrence of biochemical failure (BF), local failure, regional failure, distant metastasis (DM), institution of new unplanned anticancer treatment, or death from prostate cancer (prostate cancer specific mortality [PCSM]).
IV. To compare freedom from biochemical failure (FFBF) and TTP rates with an alternate prostate specific antigen (PSA) >= PSA nadir + 2 ng/mL definition of BF.
V. To compare local failure, regional failure, salvage therapy (i.e. institution of new unplanned anticancer treatment), DM, PCSM, and overall survival (OS) rates.
VI. Assessment of adverse events.
EXPLORATORY OBJECTIVES:
I. To compare utilities for health outcomes using the EuroQol five dimensions questionnaire (EQ-5D).
II. Paraffin-embedded tissue block, serum, plasma, whole blood, and urine for future translational research analyses for predictors of toxicity following hypofractionated or conventionally fractionated post-prostatectomy radiotherapy.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo conventional radiation therapy for 37 fractions over 7 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive androgen deprivation therapy for up to 6 months as per doctor recommendation.
ARM II: Patients undergo hypofractionated radiation therapy for 25 fractions over 5 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive androgen deprivation therapy for up to 6 months as per doctor recommendation.
After completion of study treatment, patients are followed up every 6 months for 2 years and every year for 3 years and thereafter.
Inclusion Criteria:
PRIOR TO STEP 1 REGISTRATION
Adenocarcinoma of the prostate treated primarily with radical prostatectomy
One of the following pathologic T-classifications: pT2 or pT3
One of the following pathologic N-classifications: pN0, pNX
No clinical evidence of regional lymph node metastasis
A post-radical prostatectomy study entry PSA >= 45 days after prostatectomy and within 30 days prior to step 1, < 2.0 ng/mL
No evidence of a local recurrence in the prostate fossa based on a digital rectal examination (DRE) within 60 days prior to step 1 registration
No evidence of bone metastases (M0) on bone scan (Na F positron emission tomography (PET)/CT is an acceptable substitute) within 120 days prior to step 1 registration
Zubrod performance status 0-1 within 60 days prior to step 1 registration
The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration
Willingness and ability to complete the Expanded Prostate Cancer Index Composite (EPIC) questionnaire
Only English and French-speaking patients are eligible to participate as these are the only language the EPIC has been validated in
PRIOR TO STEP 2 REGISTRATION
The EPIC must be completed in full and entered within 10 business days after step 1 registration; NRG Oncology Statistical and Data Management Center has 3 business days to score the results and send a notification to the site to proceed to step 2 randomization
Exclusion Criteria:
A post-prostatectomy PSA nadir >= 0.2 ng/mL AND Gleason >= 7 (Considered for NRG-GU002, principal investigator [PI]: Hurwitz)
pT2 with a negative surgical margin and PSA < 0.1 ng/mL
Androgen deprivation therapy started prior to prostatectomy for > 6 months (180 days) duration;
Androgen deprivation therapy started after prostatectomy and prior to step 1 registration for > 6 weeks (42 days)
Neoadjuvant chemotherapy before or after prostatectomy
Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for a minimum of 3 years and not in the pelvis; (for example, carcinoma in situ of the oral cavity is permissible if disease free for a minimum of 3 years; however, patients with prior history of bladder cancer are not allowed no matter the disease free duration); prior hematological (e.g., leukemia, lymphoma, myeloma) malignancy is not allowed
Previous chemotherapy for any other disease site if given within 3 years prior to step 1
Prior radiotherapy, including brachytherapy, to the region of the study cancer that would result in overlap of radiation therapy treatment volumes
Severe, active co-morbidity, defined as follows:
Prior allergic reaction to the study drugs involved in this protocol
History of inflammatory bowel disease, prior bowel surgeries (or colostomy) for any reason, or prior partial/radical cystectomy for any reason
Sacramento, California 95817, United States
Deerfield Beach, Florida 33442, United States
Miami, Florida 33136, United States
Elkton, Maryland 21921, United States
Brownstown, Michigan 48183, United States
Grand Rapids, Michigan 49503, United States
Lebanon, New Hampshire 03756, United States
Wilmington, North Carolina 28401, United States
Harrisburg, Pennsylvania 17109, United States
Hilton Head Island, South Carolina 29926, United States
American Fork, Utah 84003, United States
Eau Claire, Wisconsin 54703, United States
Madison, Wisconsin 53792, United States
Summit, Wisconsin 53066, United States
Montreal, Quebec H3H 2R9, Canada