Randomized Trial of Adjuvant Hormonal Therapy in Surgically Treated Prostate Cancer Patients at High Risk for Recurrence
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm I - Leuprolide + Flutamide Arm I: Patients receive leuprolide intramuscularly once every 3 months and oral flutamide three times daily for 1 year. |
Drug: Flutamide
10.8 mg intramuscularly once every 3 months for 12 months
Other Names:
Drug: Leuprolide Acetate
50 mg tablet orally daily for 12 months
Other Names:
|
No Intervention: Arm II - No Treatment Arm II: Patients receive no initial treatment. |
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Organ confined prostate cancer (stage T1-T2c) subsequent to clinical staging
-
Radical prostatectomy and bilateral lymph node dissection performed
-
Pathologic assessment of surgical specimens by MDACC pathologist
-
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
-
Radical prostatectomy performed within 90 days of enrollment and serum PSA level < 0.1ng/ml
-
Written informed consent
Exclusion Criteria:
-
Any evidence of metastatic disease confirmed prior to enrollment
-
Inability to confirm pathologic risk factors or inadequate prostatectomy (see item 4.1.5).
-
Hormonal ablation for greater than 3 months or radiotherapy for prostate cancer
-
Failure to achieve prostate specific antigen level of less than 0.1ng/ml prior to enrollment in study
-
Elevation of liver function tests 2x normal
-
Contraindication to the use of LH-RH agonists or antiandrogens
-
Active secondary malignancy (other than squamous or basal cell skin cancer) within five years prior to enrollment in study
-
Any concomitant medical condition that would make it undesirable for the 7patient to participate in the trial or jeopardize compliance with the protocol
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Texas - MD Anderson Cancer Center | Houston | Texas | United States | 77030-4009 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
- Eastern Cooperative Oncology Group
- AstraZeneca
Investigators
- Study Chair: Curtis A. Pettaway, MD, M.D. Anderson Cancer Center
- Study Chair: Michael O. Koch, MD, Indiana University Melvin and Bren Simon Cancer Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- ID97-077
- P30CA016672
- MDA-ID-97077
- E-97077
- NCI-T97-0069
- CDR0000066733
- NCI-2009-00818
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | The study terminated early with low accrual with insufficient data for analysis. |
Arm/Group Title | Arm A | Arm B |
---|---|---|
Arm/Group Description | Goserelin + Bicalutamide (one year) | No initial treatment |
Period Title: Overall Study | ||
STARTED | 30 | 34 |
COMPLETED | 18 | 22 |
NOT COMPLETED | 12 | 12 |
Baseline Characteristics
Arm/Group Title | Arm A | Arm B | Total |
---|---|---|---|
Arm/Group Description | Goserelin + Bicalutamide (one year) | No initial treatment | Total of all reporting groups |
Overall Participants | 30 | 34 | 64 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
18
60%
|
26
76.5%
|
44
68.8%
|
>=65 years |
12
40%
|
8
23.5%
|
20
31.3%
|
Sex: Female, Male (Count of Participants) | |||
Female |
0
0%
|
0
0%
|
0
0%
|
Male |
30
100%
|
34
100%
|
64
100%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
2
6.7%
|
1
2.9%
|
3
4.7%
|
Not Hispanic or Latino |
28
93.3%
|
33
97.1%
|
61
95.3%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
2
6.7%
|
1
2.9%
|
3
4.7%
|
Not Hispanic or Latino |
28
93.3%
|
33
97.1%
|
61
95.3%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
1
2.9%
|
1
1.6%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
2
6.7%
|
4
11.8%
|
6
9.4%
|
White |
26
86.7%
|
28
82.4%
|
54
84.4%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
2
6.7%
|
1
2.9%
|
3
4.7%
|
Region of Enrollment (participants) [Number] | |||
United States |
30
100%
|
34
100%
|
64
100%
|
Outcome Measures
Title | Number of Participants With Disease Free Survival at 5 Years |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
The study terminated early without any participants reaching the 5 years on study analysis point. |
Arm/Group Title | Arm I - Leuprolide + Flutamide | Arm II - No Treatment |
---|---|---|
Arm/Group Description | Arm I: Patients receive leuprolide intramuscularly once every 3 months and oral flutamide three times daily for 1 year. Flutamide: 10.8 mg intramuscularly once every 3 months for 12 months Leuprolide Acetate: 50 mg tablet orally daily for 12 months | Arm II: Patients receive no initial treatment. |
Measure Participants | 0 | 0 |
Title | Number of Wives of the Participants Having Better Than or Equal to a "Good" Quality of Life |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Arm A | Arm B |
---|---|---|
Arm/Group Description | Goserelin + Bicalutamide (one year) | No initial treatment |
Measure Participants | 30 | 34 |
Count of Participants [Participants] |
19
63.3%
|
24
70.6%
|
Title | Quality of Life for Participants |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Arm I - Leuprolide + Flutamide | Arm II - No Treatment |
---|---|---|
Arm/Group Description | Arm I: Patients receive leuprolide intramuscularly once every 3 months and oral flutamide three times daily for 1 year. Flutamide: 10.8 mg intramuscularly once every 3 months for 12 months Leuprolide Acetate: 50 mg tablet orally daily for 12 months | Arm II: Patients receive no initial treatment. |
Measure Participants | 21 | 22 |
Mental |
55
|
54
|
Physical |
49
|
49
|
Sexual Function |
5
|
28
|
Title | Markers of Prognosis |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Due to poor study accrual there were not enough data collected to be analyzed to determine the markers of prognosis. |
Arm/Group Title | Arm I - Leuprolide + Flutamide | Arm II - No Treatment |
---|---|---|
Arm/Group Description | Arm I: Patients receive leuprolide intramuscularly once every 3 months and oral flutamide three times daily for 1 year. Flutamide: 10.8 mg intramuscularly once every 3 months for 12 months Leuprolide Acetate: 50 mg tablet orally daily for 12 months | Arm II: Patients receive no initial treatment. |
Measure Participants | 0 | 0 |
Adverse Events
Time Frame | 1 Year (duration of study treatment) | |||
---|---|---|---|---|
Adverse Event Reporting Description | AEs and SAEs were only assessed and documented for participants on treatment arm A | |||
Arm/Group Title | Arm I - Leuprolide + Flutamide | Arm II - No Treatment | ||
Arm/Group Description | Arm I: Patients receive leuprolide intramuscularly once every 3 months and oral flutamide three times daily for 1 year. Flutamide: 10.8 mg intramuscularly once every 3 months for 12 months Leuprolide Acetate: 50 mg tablet orally daily for 12 months | Arm II: Patients receive no initial treatment. | ||
All Cause Mortality |
||||
Arm I - Leuprolide + Flutamide | Arm II - No Treatment | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/30 (13.3%) | 1/34 (2.9%) | ||
Serious Adverse Events |
||||
Arm I - Leuprolide + Flutamide | Arm II - No Treatment | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 6/30 (20%) | 0/0 (NaN) | ||
Blood and lymphatic system disorders | ||||
DVT | 1/30 (3.3%) | 1 | 1/0 (Infinity) | 1 |
Cardiac disorders | ||||
Chest Pain | 1/30 (3.3%) | 1 | 1/0 (Infinity) | 1 |
Gastrointestinal disorders | ||||
Inguinal Hernia | 1/30 (3.3%) | 1 | 1/0 (Infinity) | 1 |
Infections and infestations | ||||
Infection | 1/30 (3.3%) | 1 | 1/0 (Infinity) | 1 |
Renal and urinary disorders | ||||
Urinary Infection | 1/30 (3.3%) | 1 | 1/0 (Infinity) | 1 |
Skin and subcutaneous tissue disorders | ||||
Urticaria | 1/30 (3.3%) | 1 | 1/0 (Infinity) | 1 |
Other (Not Including Serious) Adverse Events |
||||
Arm I - Leuprolide + Flutamide | Arm II - No Treatment | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 25/30 (83.3%) | 0/0 (NaN) | ||
Gastrointestinal disorders | ||||
Diarrhea | 7/30 (23.3%) | 7 | 7/0 (Infinity) | 7 |
General disorders | ||||
Fatigue | 17/30 (56.7%) | 17 | 17/0 (Infinity) | 17 |
Investigations | ||||
Weight Gain | 4/30 (13.3%) | 4 | 4/0 (Infinity) | 4 |
Psychiatric disorders | ||||
Decreased Libido | 8/30 (26.7%) | 8 | 8/0 (Infinity) | 8 |
Insomnia | 4/30 (13.3%) | 4 | 4/0 (Infinity) | 4 |
Reproductive system and breast disorders | ||||
Gynecomastia | 9/30 (30%) | 9 | 9/0 (Infinity) | 9 |
Skin and subcutaneous tissue disorders | ||||
Skin Rash | 5/30 (16.7%) | 5 | 5/0 (Infinity) | 5 |
Vascular disorders | ||||
Hot Flashes | 25/30 (83.3%) | 25 | 25/0 (Infinity) | 25 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Curtis A. Pettaway, M.D.- Professor, Urology |
---|---|
Organization | UT MD Anderson Cancer Center |
Phone | 713-792-7734 |
cpettawa@mdanderson.org |
- ID97-077
- P30CA016672
- MDA-ID-97077
- E-97077
- NCI-T97-0069
- CDR0000066733
- NCI-2009-00818