Randomized Trial of Adjuvant Hormonal Therapy in Surgically Treated Prostate Cancer Patients at High Risk for Recurrence

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Terminated
CT.gov ID
NCT00003645
Collaborator
National Cancer Institute (NCI) (NIH), Eastern Cooperative Oncology Group (Other), AstraZeneca (Industry)
64
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2
213.2
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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

Study Type:
Interventional
Actual Enrollment :
64 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Randomized Prospective Trial of Adjuvant Hormonal Therapy in Surgically Treated Prostate Cancer Patients at High Risk for Recurrence
Actual Study Start Date :
Jun 14, 1999
Actual Primary Completion Date :
Mar 20, 2017
Actual Study Completion Date :
Mar 20, 2017

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:
  • Goserelin
  • Zoladex
  • Drug: Leuprolide Acetate
    50 mg tablet orally daily for 12 months
    Other Names:
  • Casodex
  • Bicalutamide
  • No Intervention: Arm II - No Treatment

    Arm II: Patients receive no initial treatment.

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    Male
    Accepts 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

    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.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00003645
    Other Study ID Numbers:
    • ID97-077
    • P30CA016672
    • MDA-ID-97077
    • E-97077
    • NCI-T97-0069
    • CDR0000066733
    • NCI-2009-00818
    First Posted:
    Jul 15, 2003
    Last Update Posted:
    Apr 28, 2020
    Last Verified:
    Apr 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by M.D. Anderson Cancer Center
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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
    2. Other Pre-specified Outcome
    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%
    3. Other Pre-specified Outcome
    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
    4. Other Pre-specified Outcome
    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

    [Not Specified]

    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
    Email cpettawa@mdanderson.org
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00003645
    Other Study ID Numbers:
    • ID97-077
    • P30CA016672
    • MDA-ID-97077
    • E-97077
    • NCI-T97-0069
    • CDR0000066733
    • NCI-2009-00818
    First Posted:
    Jul 15, 2003
    Last Update Posted:
    Apr 28, 2020
    Last Verified:
    Apr 1, 2020