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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00004054
First received: December 10, 1999
Last updated: May 21, 2014
Last verified: May 2014
  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: releasing hormone agonist therapy
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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 [ 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Biochemical control [ Time Frame: From randomization to the date of PSA failure per the ASTRO definition or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. ] [ Designated as safety issue: No ]
  • Local progression [ Time Frame: From randomization to the date of local progression or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. ] [ Designated as safety issue: No ]
  • Distant metastasis [ Time Frame: From randomization to the date of metastatic disease or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. ] [ Designated as safety issue: No ]
  • Disease free survival [ Time Frame: From randomization to the first occurrence of biochemical failure, clinical failure (local or distant), death from any cause, or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. ] [ Designated as safety issue: No ]

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: Arm 1
AS (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and Casodex or Eulexin). Androgen suppression will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of RT.
Drug: bicalutamide Drug: flutamide Drug: releasing hormone agonist therapy Radiation: radiation therapy
Experimental: Arm 2
AS (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and Casodex or Eulexin) and chemotherapy. Androgen suppression will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.
Drug: bicalutamide Drug: estramustine phosphate sodium Drug: etoposide Drug: flutamide Drug: paclitaxel Drug: releasing hormone agonist therapy Radiation: radiation therapy

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

Ages Eligible for Study:   18 Years and older
Genders 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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004054

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

Additional 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
Study First Received: December 10, 1999
Last Updated: May 21, 2014
Health Authority: United States: Federal Government

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
Androgens
Estramustine
Flutamide
Etoposide phosphate
Bicalutamide
Etoposide
Paclitaxel
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Androgen Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on August 21, 2014