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:

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 tumour cells. PURPOSE: This randomized phase III trial studies androgen-deprivation therapy and radiation therapy in treating patients with prostate cancer.

Trial Description

Primary Outcome:

  • Overall Survival
Secondary Outcome:
  • Cause-specific survival
  • Distant metastasis-free survival
  • Biochemical failure by the Phoenix definition (PSA ≥ 2 ng/mL over the nadir PSA)
  • Incidence of "acute" adverse events as assessed by the Common Toxicity Criteria for Adverse Effects (CTCAE) current version
  • Time to "late" grade 3+ adverse events as assessed by CTCAE current version
  • Prostate cancer-specific HRQOL change as measured by the EPIC-26 (bowel or urinary domain)
  • Fatigue status as measured by the Patient-Reported Outcome Measurement Information System (PROMIS) fatigue-domain change score
  • Assessment and comparison of Quality Adjusted Life Years (QALYs)
OBJECTIVES:
Primary
  • 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. Secondary
  • 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, tumour 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 multicentre study. Patients are stratified according to moderate- to high-risk groups as listed in the Disease Characteristics of this abstract, type of radiation therapy 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 radiation therapy and continuing for 6 or 32 months. Radiation Therapy begins within 8 weeks after beginning LHRH agonist/antagonist injection.
  • Arm I: Patients undergo high-dose radiation therapy of the prostate and seminal vesicles using intensity-modulated radiation therapy (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 radiation therapy (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 tumour 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.
  • View this trial on ClinicalTrials.gov

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Resources

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