A Randomized Phase III Trial of Hypofractionated Post-Prostatectomy Radiation Therapy (HYPORT) Versus Conventional Post-Prostatectomy Radiation Therapy (COPORT)
Overview
- Phase
- Phase 3
- Intervention
- Laboratory Biomarker Analysis
- Conditions
- Not specified
- Sponsor
- NRG Oncology
- Enrollment
- 296
- Locations
- 482
- Primary Endpoint
- Change in Urinary Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years
- Status
- Completed
- Last Updated
- last month
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •PRIOR TO STEP 1 REGISTRATION
- •Adenocarcinoma of the prostate treated primarily with radical prostatectomy
- •Any type of radical prostatectomy will be permitted, including retropubic, perineal, laparoscopic, or robotically assisted; there is no time limit for the date of radical prostatectomy
- •One of the following pathologic T-classifications: pT2 or pT3
- •Patients with positive surgical margins are eligible
- •One of the following pathologic N-classifications: pN0, pNX
- •If a lymph node dissection is performed, the number of lymph nodes removed per side of the pelvis and the extent of the pelvic lymph node dissection (obturator versus \[vs.\] extended lymph node dissection) should be noted whenever possible
- •No clinical evidence of regional lymph node metastasis
- •Computed tomography (CT) (with contrast if renal function is acceptable; a noncontrast CT is permitted if the patient is not a candidate for contrast), magnetic resonance imaging (MRI), nodal sampling, or dissection of the pelvis within 120 days prior to step 1 registration
- •Patients with pelvic lymph nodes equivocal or questionable by imaging are eligible if the nodes are =\< 1 cm in the short axis
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;
- •Note: The use of finasteride or dutasteride (+/- tamsulosin) for longer periods prior to prostatectomy is acceptable
- •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:
Arms & Interventions
Arm I (conventional radiation therapy)
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.
Intervention: Laboratory Biomarker Analysis
Arm I (conventional radiation therapy)
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.
Intervention: Quality-of-Life Assessment
Arm I (conventional radiation therapy)
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.
Intervention: Radiation Therapy
Arm II (hypofractionated radiation therapy
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.
Intervention: Hypofractionated Radiation Therapy
Arm II (hypofractionated radiation therapy
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.
Intervention: Laboratory Biomarker Analysis
Arm II (hypofractionated radiation therapy
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.
Intervention: Quality-of-Life Assessment
Outcomes
Primary Outcomes
Change in Urinary Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years
Time Frame: Baseline (randomization), 2 years
The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The urinary domain contains 12 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL.
Change in Bowel Domain of the Expanded Prostate Cancer Index (EPIC) at Two Years
Time Frame: Baseline, 2 years
The EPIC is a prostate cancer health-related quality of life (HRQOL) self-administered instrument measuring patient-reported urinary, bowel, sexual, and hormonal symptoms related to prostate cancer treatments. Response options for each item form a Likert scale with scores transformed linearly to a 0-100 scale. Domain scores are also on a 0-100 scale with higher scores representing better HRQOL. The bowel domain contains 14 items. Change from baseline is calculated by subtracting baseline from later score, with a positive change score indicating increased HRQOL.
Secondary Outcomes
- Percentage of Participants With Biochemical Failure(From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years.)
- Number of Participants With Grade 3+ Adverse Events(From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.)
- Change in Urinary Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of Radiation Therapy (RT), 6 Months, 1 and 5 Years(Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of androgen deprivation therapy (ADT) (optional) and RT.)
- Percentage of Participants With Local-Regional Failure(From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.)
- Percentage of Participants Receiving Salvage Therapy(From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.)
- Change in Bowel Domain Score of the Expanded Prostate Cancer Index (EPIC) at End of RT, 6 Months, 1 and 5 Years(Baseline, end of RT, then 6 months,1 and 5 years from the start of RT (5 year time point has not yet been reached). RT dates depend on timing and duration of ADT (optional) and RT.)
- Percentage of Participants With Progression(From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.)
- Percentage of Participants With Distant Metastasis(From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.)
- Percentage of Participants Who Died From Prostate Cancer (Prostate Cancer Specific Mortality)(From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.)
- Percent of Participants Alive (Overall Survival)(From randomization to last follow-up. Maximum follow-up at time of analysis was 3.0 years. Two-year rates reported here. Follow-up schedule: end of RT, then 6, 12, 18, 24 months from start of RT, then yearly.)