Androgen-Deprivation Therapy and Radiation Therapy in Treating Patients With Prostate Cancer

Official Title

Androgen Deprivation Therapy and High Dose Radiation Therapy With or Without Whole-Pelvic Radiation Therapy in Unfavorable Intermediate or Favorable High Risk Prostate Cancer: A Phase III Randomized Trial

Summary:

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 tumour cells.

Trial Description

Primary Outcome:

• Overall survival

Secondary Outcome:

• Assessment and comparison of Quality Adjusted Life Years defined by the weighted sum of different time episodes added up to a total quality-adjusted survival time (closed to patient accrual 3/9/15)
• Biochemical failure by the Phoenix definition (PSA >= 2 ng/mL over the nadir PSA)
• Cause-specific survival
• Collection of paraffin-embedded tissue blocks, plasma, whole blood, serum, and urine for planned and future translational research analyses
• Distant metastasis-free survival of these patients
• Fatigue status as measured by the PROMIS fatigue-domain change score (closed to patient accrual 3/9/15)
• Incidence of "acute" adverse events defined as the first occurrence of worst severity of the adverse event, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) current version
• Prostate cancer-specific HRQOL change as measured by the EPIC-26 (bowel or urinary domain) (closed to patient accrual 3/9/15)
• Time to "late" adverse events measured from the time protocol treatment started to the time of the worst late grade 3+ adverse event using the CTCAE

PRIMARY OBJECTIVE:

• 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 "favourable" 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 radiation therapy (IMRT) or external-beam RT (EBRT) with a high-dose rate (HDR) or a permanent prostate (radioactive seed) implant (PPI) boost.

SECONDARY OBJECTIVES:

• Demonstrate that prophylactic WPRT improves biochemical control.
• Distant metastasis (DM)-free survival.
• 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). (closed to patient accrual 3/9/15)
• 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, tumour necrosis factor [TNF]-alpha, and C-reactive protein). (closed to patient accrual 3/9/15)
• 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)
• 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:
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 radiation therapy and continuing for 6 or 32 months. Radiation Therapy begins within 8-10 weeks after beginning LHRH agonist/antagonist injection.

ARM I: Patients undergo high-dose radiation therapy 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.

View this trial on ClinicalTrials.gov