Prostate Cancer
Conditions
Keywords
stage I prostate cancer, stage II prostate cancer
Brief summary
RATIONALE: Testosterone can stimulate the growth of prostate cancer cells. Hormone therapy using leuprolide and flutamide may fight prostate cancer by reducing the production of testosterone. It is not yet known whether receiving leuprolide and flutamide is more effective than receiving no further therapy. PURPOSE: Randomized phase III trial to determine the effectiveness of hormone therapy in treating patients who have stage I or stage II prostate cancer that is at high risk of recurrence and who have already undergone surgery.
Detailed description
OBJECTIVES: * Determine the effect of one year of adjuvant hormonal ablation on disease-free survival at 5 years in node-negative radical prostatectomy patients at high risk for progression. * Determine the effect of this treatment on the incidence of androgen independent prostate cancer and on disease specific and overall survival. * Determine the impact of one year of total androgen ablation on quality of life and serum testosterone levels. * Assess differences in quality of life between wives of patients in the androgen ablation condition compared to wives of patients in the control condition. * Obtain blood samples from patients at high risk for failure post-prostatectomy to evaluate serum markers of prognosis. OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms. * Arm I: Patients receive leuprolide intramuscularly once every 3 months and oral flutamide three times daily for 1 year. * Arm II: Patients receive no initial treatment. Quality of life is assessed every 6 months for 5 years. Quality of life of wives/partners of patients is assessed every 6 months for two years. Patients are followed every 3 months for 1 year and then every 6 months for 4 years. PROJECTED ACCRUAL: A total of 496 patients (248 per treatment arm) will be accrued for this study within 3.5 years.
Interventions
DRUGFlutamide
10.8 mg intramuscularly once every 3 months for 12 months
DRUGLeuprolide Acetate
50 mg tablet orally daily for 12 months
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
AstraZeneca
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
1. Organ confined prostate cancer (stage T1-T2c) subsequent to clinical staging 2. Radical prostatectomy and bilateral lymph node dissection performed 3. Pathologic assessment of surgical specimens by MDACC pathologist 4. High risk of clinical or biochemical failure post prostatectomy (must fulfill one of the following criteria): pathology; a) Gleason grade sum score greater than or equal to 8, b) Seminal vesicle involvement, c) Extraprostatic extension with positive surgical margins and Gleason greater than or equal to 7 5. Radical prostatectomy performed within 90 days of enrollment and serum PSA level \< 0.1ng/ml 6. Written informed consent
Exclusion criteria
1. Any evidence of metastatic disease confirmed prior to enrollment 2. Inability to confirm pathologic risk factors or inadequate prostatectomy (see item 4.1.5). 3. Hormonal ablation for greater than 3 months or radiotherapy for prostate cancer 4. Failure to achieve prostate specific antigen level of less than 0.1ng/ml prior to enrollment in study 5. Elevation of liver function tests 2x normal 6. Contraindication to the use of LH-RH agonists or antiandrogens 7. Active secondary malignancy (other than squamous or basal cell skin cancer) within five years prior to enrollment in study 8. Any concomitant medical condition that would make it undesirable for the 7patient to participate in the trial or jeopardize compliance with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Disease Free Survival at 5 Years | Beginning of the study up to 5 years | To determine if one year of adjuvant hormonal ablation in node negative radical prostatectomy patients at high risk for progression will result in an improvement in disease-free survival at five years. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Wives of the Participants Having Better Than or Equal to a Good Quality of Life | 2 years | To measure the differences in quality of life between wives of participants in the androgen ablation condition compared to wives of patients in the control condition by using quality of life assessments. The following questionnaires were completed in the clinic setting and used to assess Health related (HRQoL): Medical Outcomes Study 36-Item Short Form (SF-36), University of California-Los Angeles Sexual Function Scale (UCLA-SFS), and Southwest Oncology Group Treatment-Specific Symptoms Scale (SWOG-TSSS). The SF-36 was analysed using a composite score for each of physical health and mental health. SF-36, UCLA-SFS, SWOGTSSS were combined to classify participants' quality of life. |
| Quality of Life for Participants | 1 year | To determine the impact of one year of total androgen ablation on quality of life mentally, physically and sexual function. The following questionnaires were completed by patients in the clinic setting and used to assess HRQoL: Medical Outcomes Study 36-Item Short Form (SF-36) and University of California-Los Angeles Sexual Function Scale (UCLA-SFS). To score the SF-36, scales are standardized with a scoring algorithm or by the SF-36v2 scoring software to obtain a score ranging from 0 to 100. Higher scores indicate better quality of life. |
| Markers of Prognosis | 1 year after treatment | To obtain blood/tissue samples from patients at high risk for failure post prostatectomy to evaluate markers of prognosis. |
Countries
United States
Participant flow
Pre-assignment details
The study terminated early with low accrual with insufficient data for analysis.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Goserelin + Bicalutamide (one year) | 30 |
| Arm B No initial treatment | 34 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 1 |
| Overall Study | Lost to Follow-up | 7 | 8 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Arm A | Total | Arm B |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 20 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 44 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 61 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 26 Participants | 54 Participants | 28 Participants |
| Region of Enrollment United States | 30 participants | 64 participants | 34 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 30 Participants | 64 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 30 | 1 / 34 |
| other Total, other adverse events | 25 / 30 | 0 / 0 |
| serious Total, serious adverse events | 6 / 30 | 0 / 0 |
Outcome results
Primary
Number of Participants With Disease Free Survival at 5 Years
To determine if one year of adjuvant hormonal ablation in node negative radical prostatectomy patients at high risk for progression will result in an improvement in disease-free survival at five years.
Time frame: Beginning of the study up to 5 years
Population: The study terminated early without any participants reaching the 5 years on study analysis point.
Other Pre-specified
Markers of Prognosis
To obtain blood/tissue samples from patients at high risk for failure post prostatectomy to evaluate markers of prognosis.
Time frame: 1 year after treatment
Population: Due to poor study accrual there were not enough data collected to be analyzed to determine the markers of prognosis.
Other Pre-specified
Number of Wives of the Participants Having Better Than or Equal to a Good Quality of Life
To measure the differences in quality of life between wives of participants in the androgen ablation condition compared to wives of patients in the control condition by using quality of life assessments. The following questionnaires were completed in the clinic setting and used to assess Health related (HRQoL): Medical Outcomes Study 36-Item Short Form (SF-36), University of California-Los Angeles Sexual Function Scale (UCLA-SFS), and Southwest Oncology Group Treatment-Specific Symptoms Scale (SWOG-TSSS). The SF-36 was analysed using a composite score for each of physical health and mental health. SF-36, UCLA-SFS, SWOGTSSS were combined to classify participants' quality of life.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I - Leuprolide + Flutamide | Number of Wives of the Participants Having Better Than or Equal to a Good Quality of Life | 19 Participants |
| Arm II - No Treatment | Number of Wives of the Participants Having Better Than or Equal to a Good Quality of Life | 24 Participants |
Other Pre-specified
Quality of Life for Participants
To determine the impact of one year of total androgen ablation on quality of life mentally, physically and sexual function. The following questionnaires were completed by patients in the clinic setting and used to assess HRQoL: Medical Outcomes Study 36-Item Short Form (SF-36) and University of California-Los Angeles Sexual Function Scale (UCLA-SFS). To score the SF-36, scales are standardized with a scoring algorithm or by the SF-36v2 scoring software to obtain a score ranging from 0 to 100. Higher scores indicate better quality of life.
Time frame: 1 year
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm I - Leuprolide + Flutamide | Quality of Life for Participants | Mental | 55 score on a scale |
| Arm I - Leuprolide + Flutamide | Quality of Life for Participants | Sexual Function | 5 score on a scale |
| Arm I - Leuprolide + Flutamide | Quality of Life for Participants | Physical | 49 score on a scale |
| Arm II - No Treatment | Quality of Life for Participants | Physical | 49 score on a scale |
| Arm II - No Treatment | Quality of Life for Participants | Mental | 54 score on a scale |
| Arm II - No Treatment | Quality of Life for Participants | Sexual Function | 28 score on a scale |