Androgen-Deprivation Therapy and Radiation Therapy in Treating Patients With Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT01368588|
Recruitment Status : Recruiting
First Posted : June 8, 2011
Last Update Posted : May 19, 2017
RATIONALE: 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.
PURPOSE: This randomized phase III trial studies androgen-deprivation therapy and radiation therapy in treating patients with prostate cancer.
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Radiation: radiation therapy Radiation: Whole-pelvic radiotherapy (WPRT)||Phase 3|
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- 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 (P) and seminal vesicle (SV) radiation therapy (RT) using intensity-modulated RT (IMRT) or external-beam RT (EBRT) with a high-dose rate (HDR) or a permanent prostate (radioactive seed) implant (PPI) boost.
- Demonstrate that prophylactic WPRT improves biochemical control.
- Determine the distant metastasis (DM)-free survival.
- Determine the cause-specific survival (CSS).
- Compare acute and late treatment-adverse events between patients receiving NADT and WPRT versus NADT, P, and SV RT.
- 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).
- Determine whether more aggressive treatment (Arm 2, NADT + WPRT) is associated with a greater increase in fatigue (PROMIS Fatigue Short Form) from baseline to last week of treatment, and a greater increase in circulating inflammatory markers (IL-1, IL-1ra, IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein).
- 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).
- 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.
- Collect paraffin-embedded tissue blocks, plasma, whole blood, and urine for planned and future translational research analyses.
OUTLINE: This is a multicenter study. Patients are stratified according to moderate- to high-risk groups as listed in the Disease Characteristics of this abstract, type of radiotherapy boost (IMRT vs brachytherapy [Low-dose rate (LDR) using PPI or HDR]), and duration of androgen-deprivation therapy (short-term [6 months] vs long-term [32 months]). Patients are randomized to 1 of 2 treatment arms.
All patients receive neoadjuvant androgen-deprivation therapy comprising bicalutamide orally (PO) once daily or flutamide PO thrice daily 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 weeks after beginning LHRH agonist/antagonist injection.
- Arm I: Patients undergo high-dose radiotherapy of the prostate and seminal vesicles using intensity-modulated radiotherapy (IMRT)* or 3D-conformal radiation therapy (3D-CRT)* once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo permanent prostate implant (PPI) brachytherapy or high-dose rate brachytherapy (iodine I 125 or palladium Pd 103 may be used as the radioisotope).
- Arm II: Patients undergo whole-pelvic radiotherapy (WPRT)* (3D-CRT or IMRT) once daily, 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.
Patients may undergo blood and urine sample collection for correlative studies. Primary tumor tissue samples may also be collected.
Patients may complete the Expanded Prostate Cancer Index Composite (EPIC), the PROMIS-Fatigue Short Form, and the EuroQol (EQ-5D) quality-of-life (QOL) questionnaires at baseline and periodically during treatment. Patients who participate in the QOL portion of the study must also agree to periodic blood collection.
After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 3 years, and then yearly thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||2580 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||July 2011|
|Estimated Primary Completion Date :||July 2027|
Active Comparator: Arm I
Patients undergo high-dose radiotherapy of the prostate and seminal vesicles using intensity-modulated radiotherapy (IMRT)* or 3D-conformal radiation therapy (3D-CRT)* once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo permanent prostate implant (PPI) brachytherapy or high-dose rate brachytherapy (I 125 or Pd 103 may be used as the radioisotope).
Radiation: radiation therapy
Undergo RT using IMRT or 3D-CRT
Experimental: Arm II
Patients undergo whole-pelvic radiotherapy (WPRT)* (3D-CRT or IMRT) once daily, 5 days a week, for approximately 9 weeks. Patients may also undergo brachytherapy as in arm I.
Radiation: Whole-pelvic radiotherapy (WPRT)
Undergo whole-pelvic radiotherapy (WPRT)
- Overall Survival [ Time Frame: From date of randomization to the date of death. ]
- Cause-specific survival [ Time Frame: From date of randomization to the date of death due to prostate cancer. ]
- Distant metastasis-free survival [ Time Frame: From date of randomization to the date of first documented distant metastasis or date of first clinical and/or radiographic appearance of disseminated disease. ]
- Biochemical failure by the Phoenix definition (PSA ≥ 2 ng/mL over the nadir PSA) [ Time Frame: From date of randomization to the date of first biochemical failure by phoenix definition within 5 years of randomization. ]
- Incidence of "acute" adverse events as assessed by the Common Toxicity Criteria for Adverse Effects (CTCAE) current version [ Time Frame: From protocol treatment start date to the date of first occurrence of worst severity of the adverse event </= 30 days from completion of radiation therapy. ]
- Time to "late" grade 3+ adverse events as assessed by CTCAE current version [ Time Frame: From protocol treatment start date to the date of the first late grade 3+ adverse event occurring more than 30 days after the completion of radiation therapy. ]
- Prostate cancer-specific HRQOL change as measured by the EPIC-26 (bowel or urinary domain) [ Time Frame: Date when baseline EPIC-26 completed to 6 months post radiation therapy, 1 year post radiation therapy and 5 years post radiation therapy. ]
- Fatigue status as measured by the Patient-Reported Outcome Measurement Information System (PROMIS) fatigue-domain change score [ Time Frame: From the date when the baseline PROMIS is completed to the last week of treatment. ]
- Assessment and comparison of Quality Adjusted Life Years (QALYs) [ Time Frame: From the baseline QALYs assessment to the last week of radiation therapy (RT), 3 months post RT, 6 months post RT, 1 year post RT and 5 years post RT. ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01368588
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|Principal Investigator:||Mack Roach, MD||University of California, San Francisco|