A Randomized Phase III Study Comparing Androgen Suppression and Elective Pelvic Nodal Irradiation Followed by High Dose 3-D Conformal Boost Versus Androgen Suppression and Elective Pelvic Nodal Irradiation Followed by 125-Iodine Brachytherapy Implant Boost for Patients With Intermediate and High Risk Localized Prostate Cancer
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Prostate Cancer
- Sponsor
- University of British Columbia
- Enrollment
- 400
- Locations
- 1
- Primary Endpoint
- The primary end point of this trial is 5 year actuarial freedom from biochemical recurrence (5 year bNED) using the Houston definition of biochemical failure.
- Last Updated
- 12 years ago
Overview
Brief Summary
The purpose of this trial is to compare two similar treatments for patients diagnosed with prostate cancer. The two treatment arms being compared are: (Standard Arm) hormone therapy, which will prevent the production of the male hormone, testosterone, by the testicles, and pelvic external beam radiation therapy (EBRT) followed by a high-dose, conformal EBRT boost versus (Investigational Arm) hormone therapy and pelvic EBRT followed by a brachytherapy boost (implantation of radioactive iodine sources or "seeds" into the prostate).
The hypothesis of this trial is that more patients may experience 5 year actuarial freedom from biochemical recurrence of their prostate cancer following treatment with the investigational arm. Biochemical failure is declared on the date when the post treatment prostate specific antigen (PSA) is > 2 ng/mL above the lowest level previously recorded.
Detailed Description
Patients will be randomly assigned with equal probability to one or two treatment arms, Arm 1 or Arm 2, where the interventions associated with these Arms are as follows: Arm 1: Neoadjuvant, concurrent and adjuvant androgen suppression, elective pelvic nodal irradiation (EPNI), high dose conformal EBRT boost to the prostate, and appropriate secondary interventions at failure. Arm 2: Neoadjuvant, concurrent and adjuvant androgen suppression, elective pelvic nodal irradiation (EPNI), permanent 125-Iodine brachytherapy boost to the prostate, and appropriate secondary interventions at failure. If a patient is assigned to Arm 1, the radiation oncologist will initiate androgen suppression and monitor clinical and biochemical response. After an 8-month duration of neoadjuvant androgen suppression, the patient will undergo a course of elective pelvic nodal irradiation (EPNI) to a volume encompassing the prostate gland, seminal vesicles and regional lymph nodes. The pelvic irradiation will be followed by a dose-escalated 3-D conformal EBRT boost to the prostate with appropriate margins. The total radiation dose to the regional lymphatics is 46 Gy and prostate dose is 78 Gy at the ICRU reference point with a minimum dose to the PTV of \> 74 Gy. Androgen suppression is maintained throughout radiation therapy and following the completion of radiation therapy until the patient has received a total duration of androgen suppression of 12 months including the neoadjuvant phase. If the patient is assigned to Arm 2, the radiation oncologist will initiate androgen suppression and monitor clinical and biochemical response. After an 8-month duration of neoadjuvant androgen suppression, the patient will undergo a course of elective pelvic nodal irradiation (EPNI) to a volume encompassing the prostate gland, seminal vesicles and regional lymph nodes. The total radiation dose to the regional lymphatics is 46 Gy. Two weeks following the completion of the pelvic irradiation, the patient will undergo a permanent 125-Iodine brachytherapy prostate implant at the facilities of the participating institution by a team of healthcare professionals lead by a Radiation Oncologist with experience in prostate brachytherapy. To be eligible to participate, the institution must have done at least 25 cases of prostate brachytherapy with stranded sources. The minimal peripheral dose (MPD) to the prostate gland from the implant will be 115 Gy. A modified peripheral loading technique will be used in an effort to maintain the periurethral dose to \< 150% of the MPD. Androgen suppression is maintained throughout radiation therapy until the patient has received a total duration of androgen suppression of 12 months including the neoadjuvant phase. All patients randomized are part of the analysis. The patient remains on study whether or not protocol treatment defined for the assigned arm is completed. The end of the primary intervention is defined as 18 months following the start of neoadjuvant androgen suppression in both arms. Secondary Objectives: Overall survival, metastasis-free survival, pathological local control, incidence of acute and late side effects and complications associated with the treatment interventions, effect of the planned interventions on QOL and rate of testosterone recovery.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically-proven prostate cancer stage T1c -T3a (UICC 1997).
- •Patients with clinically organ-confined disease must meet the Canadian consensus definition of intermediate risk disease (i.e any one or more of: CS = T2b \[UICC1997 = bilateral palpable intra-capsular disease\], GS = 7, or iPSA \>10 and 20).
- •Patients with Gleason sum 8 and/or PSA \> 20 must have a CT pelvis, and nuclear medicine bone scan showing no evidence of nodal (N0) or distant metastases (M0).
- •Registration must occur within 36 weeks of biopsy.
- •Patients with clinical or pathological evidence of seminal vesicle invasion (stage T3b) or involvement of adjacent pelvic organs/structures (stage T4) are not eligible.
- •Pre-intervention PSA must not exceed 40 ng ml-
- •Patients must have a chest x-ray and the following blood tests within four weeks of registration: PSA, PAP, testosterone, CBC, electrolytes, BUN, creatinine, AST, LDH and alkaline phosphatase. Patients with values for one or more of these tests that fall outside the normal range will not necessarily be ineligible, however, their eligibility will need to be reviewed by the study coordinator.
- •Patients must have an ECG within four weeks of registration. Patients with ECGs judged to be significantly abnormal require a consultation with a cardiologist to ascertain their suitability for general or spinal anesthesia.
- •Patients judged clinically to have a prostate volume \> 65 cm3 prior to starting androgen suppression must have a transrectal ultrasound for volume estimation. Patients with TRUS prostate volumes \> 75 cm3 prior to starting androgen suppression are not eligible for the study.
- •Patients may have been started on neoadjuvant androgen suppression prior to registration provided:
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
The primary end point of this trial is 5 year actuarial freedom from biochemical recurrence (5 year bNED) using the Houston definition of biochemical failure.
Time Frame: 5 years
Secondary Outcomes
- This trial is also intended to determine overall survival, metastasis-free survival, pathological local control, incidence of acute and late side effects and complications associated with the treatment interventions, effect of the planned interventions.(5 years)