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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00004054
First Posted: January 27, 2003
Last Update Posted: December 12, 2017
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.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
  Purpose

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.


Condition Intervention Phase
Prostate Cancer Drug: bicalutamide Drug: estramustine phosphate sodium Drug: etoposide Drug: flutamide Drug: paclitaxel Drug: Luteinizing hormone releasing hormone [LHRH] agonist Radiation: Radiation therapy Drug: warfarin Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 397
Study Start Date: January 2000
Study Completion Date: November 2013
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
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: 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: 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.
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.
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
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

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004054


  Show 54 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Howard M. Sandler, MD University of Michigan Cancer Center
  More Information

Publications:
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00004054     History of Changes
Other Study ID Numbers: RTOG-9902
CDR0000067250
RTOG-DEV-1020
First Submitted: December 10, 1999
First Posted: January 27, 2003
Results First Submitted: December 24, 2014
Results First Posted: January 7, 2015
Last Update Posted: December 12, 2017
Last Verified: November 2017

Keywords provided by Radiation Therapy Oncology Group:
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Paclitaxel
Etoposide
Etoposide phosphate
Bicalutamide
Albumin-Bound Paclitaxel
Estramustine
Flutamide
Hormones
Prolactin Release-Inhibiting Factors
Warfarin
Androgens
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anticoagulants