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Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00004054
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : January 7, 2015
Last Update Posted : October 22, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Tracking Information
First Submitted Date  ICMJE December 10, 1999
First Posted Date  ICMJE January 27, 2003
Results First Submitted Date  ICMJE December 24, 2014
Results First Posted Date  ICMJE January 7, 2015
Last Update Posted Date October 22, 2020
Study Start Date  ICMJE January 2000
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 24, 2014)
Overall Survival (5-year Rate Reported) [ Time Frame: From the date of randomization to the date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. ]
Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at date of last contact. This analysis was planned to occur when all patients had been potentially followed for 5 years.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2017)
  • Rate of Biochemical Failure at 5 Years [ Time Frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years. ]
    Biochemical failure uses the American Society for Radiation Oncology (ASTRO) definition of prostate-specific antigen (PSA) rises on three consecutive occasions, with biochemical failure date being midway between the last non-rising PSA and the first rise in PSA. Time to biochemical failure is defined as time from randomization to biochemical failure, last known follow-up (censored), or death (competing risk). Biochemical failure rates are estimated using the cumulative incidence method.
  • Rate of Local Progression at 5 Years [ Time Frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years. ]
    Local progression is defined as documented clinical local and/or regional progression. Time to local progression is defined as time from randomization to local progression, last known follow-up (censored), or death (competing risk). Local progression rates are estimated using the cumulative incidence method.
  • Rate of Distant Metastasis at Five Years [ Time Frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years. ]
    Distant metastasis (DM) is defined as documented metastatic disease. Time to distant metastasis is defined as time from randomization to distant metastatic disease, last known follow-up (censored), or death (competing risk). Distant metastasis rates are estimated using the cumulative incidence method.
  • Disease-free Survival Rate at 5 Years [ Time Frame: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years. ]
    Disease-free survival (DFS) was measured from the date of randomization to the date of documentation of progression (local, distant, biochemical failure), death, or last follow-up (censored). The Kaplan-Meier method was used to estimate DFS rates.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer
Official Title  ICMJE A Phase III Protocol of Androgen Suppression (AS) and Radiation Therapy (RT) vs AS and RT Followed by Chemotherapy With Paclitaxel, Estramustine, and Etoposide (TEE) for Localized, High-Risk, Prostate Cancer
Brief Summary

RATIONALE: Hormones can stimulate the production of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy plus radiation therapy is more effective with or without combination chemotherapy for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy plus radiation therapy with or without combination chemotherapy in treating patients who have prostate cancer.

Detailed Description

OBJECTIVES:

  • Compare the efficacy of androgen suppression and radiotherapy with or without subsequent paclitaxel, estramustine, and etoposide, in terms of overall and disease-free survival, biochemical and local control, and freedom from distant metastasis, in patients with localized high-risk prostate cancer.
  • Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to prostate-specific antigen level (≤ 10 ng/mL vs 11-100 ng/mL), tumor stage (T1-2 vs T3-4), Gleason score (7 vs 8-10), and prior hormone use (yes vs no). Patients are randomized to one of two treatment arms.

All patients receive androgen suppression comprising a luteinizing hormone-releasing hormone (LHRH) agonist AND bicalutamide OR flutamide for 4 months. Beginning 8 weeks after the initiation of androgen suppression, all patients undergo radiotherapy once daily, 5 days a week, for 7-8 weeks. Patients who received prior androgen suppression therapy count time to radiotherapy from start date of prior hormonal therapy.

  • Arm I: Patients continue androgen suppression therapy (LHRH agonist only) for approximately 20 more months after radiotherapy is completed.
  • Arm II: Patients continue therapy as in arm I and receive chemotherapy beginning 28 days after completing radiotherapy. Chemotherapy comprises oral estramustine 3 times daily and oral etoposide twice daily on days 1-14 and paclitaxel IV over 1 hour on day 2. Chemotherapy repeats every 21 days for 4 courses.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,440 patients will be accrued for this study within 6 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: bicalutamide
    Administered orally at a dose of one 50mg tablet per day. Begins 8 weeks prior to radiotherapy and continues throughout radiotherapy.
    Other Name: Casodex
  • Drug: estramustine phosphate sodium
    280 mg three times a day for 14 days and repeated every 3 weeks for 4 cycles
  • Drug: etoposide
    50 mg/m^2 in divided doses b.i.d. for 14 days and repeated every 3 weeks for 4 cycles
  • Drug: flutamide
    Administered orally at a dose of two 125 mg capsules three times a day for a total daily dose of 750 mg. Begins 8 weeks prior to radiotherapy and continues throughout radiotherapy.
    Other Name: Eulexin
  • Drug: paclitaxel
    135 mg/m^2 given as a 1-hour infusion (on day 2 of each cycle) and repeated every 3 weeks for 4 cycles
  • Drug: Luteinizing hormone releasing hormone [LHRH] agonist
    Releasing hormone agonists (such as leuprolide, goserelin, buserelin, triptorelin) will be given for 4 months
  • Radiation: Radiation therapy
    Radiation will begin 8 weeks following the initiation of hormone administration: 46.8 Gy to the regional lymphatics followed by a 23.4 Gy boost to the prostate to bring the total dose to the prostate to 70.2 Gy. Daily tumor doses will be 1.8 Gy per day, 5 days per week x 7-8 weeks.
  • Drug: warfarin
    To keep international normalized ratio (INR) > 1.5 and < 2.5; begins with the start of chemotherapy and will be given continuously until 4 weeks after the end of the fourth cycle of chemotherapy
    Other Name: Coumadin
Study Arms  ICMJE
  • Experimental: Hormones and RT
    Androgen suppression (AS) (Luteinizing hormone releasing hormone agonist and bicalutamide [Casodex] or flutamide [Eulexin]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide [Casodex] or flutamide [Eulexin]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT).
    Interventions:
    • Drug: bicalutamide
    • Drug: flutamide
    • Drug: Luteinizing hormone releasing hormone [LHRH] agonist
    • Radiation: Radiation therapy
  • Experimental: Hormones and RT plus Chemotherapy
    AS (LHRH agonist and bicalutamide [Casodex] or flutamide [Eulexin]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide [Casodex] or flutamide [Eulexin]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin [Coumadin®]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.
    Interventions:
    • Drug: bicalutamide
    • Drug: estramustine phosphate sodium
    • Drug: etoposide
    • Drug: flutamide
    • Drug: paclitaxel
    • Radiation: Radiation therapy
    • Drug: warfarin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 21, 2014)
397
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE November 2013
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically proven prostate cancer at high risk for relapse as determined by either of the following:

    • Prostate-specific antigen (PSA) 20-100 ng/mL and Gleason score at least 7 (any T stage)
    • Clinical stage at least T2, Gleason score at least 8, and PSA no greater than 100 ng/mL
  • Negative lymph nodes
  • No metastatic disease

PATIENT CHARACTERISTICS:

Age:

  • Over 18

Performance status:

  • Zubrod 0 or 1

Life expectancy:

  • Not specified

Hematopoietic:

  • White blood cell (WBC) count of at least 3,000/mm^3
  • Platelet count at least 130,000/mm^3
  • Hemoglobin at least 11.4 g/dL

Hepatic:

  • Aspartate aminotransferase (AST) no greater than 2 times upper limit of normal

Renal:

  • Creatinine no greater than 2.5 mg/dL

Other:

  • No other invasive cancer within the past 5 years except superficial nonmelanomatous skin cancer
  • No major medical or psychiatric illness that would preclude study participation
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • At least 5 years since prior chemotherapy

Endocrine therapy:

  • At least 60 days since prior finasteride for prostatic hypertrophy
  • At least 90 days since prior testosterone
  • No more than 30 days since initiation of prior pharmacologic androgen ablation for prostate cancer

Radiotherapy:

  • No prior pelvic radiotherapy
  • No concurrent intensity-modulated radiotherapy

Surgery:

  • No prior radical prostatectomy
  • No prior cryosurgery for prostate cancer
  • No prior orchiectomy
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00004054
Other Study ID Numbers  ICMJE RTOG-9902
CDR0000067250
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Radiation Therapy Oncology Group
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE Radiation Therapy Oncology Group
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Howard M. Sandler, MD University of Michigan Rogel Cancer Center
PRS Account Radiation Therapy Oncology Group
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP