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Prostate CancerPhase 3NCT00004054

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

A Phase 3 study testing bicalutamide, estramustine phosphate sodium and etoposide in people with Prostate Cancer, run by Radiation Therapy Oncology Group at 54 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
bicalutamide, estramustine phosphate sodium and etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
397 participants
Where
54 sitesin 2 countries
Study dates
Jan 2000to Nov 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

54 sites in 2 countries.

54 sites in 2 countries

United States52 sites

  • Akron General Medical Center

    Akron, Ohio, 44302

  • Akron City Hospital

    Akron, Ohio, 44304

  • John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital

    Allentown, Pennsylvania, 18105

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109-0010

  • Anne Arundel Oncology Center

    Annapolis, Maryland, 21401

  • Greater Baltimore Medical Center and Cancer Center

    Baltimore, Maryland, 21204

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • St. Luke's Hospital Cancer Center

    Bethlehem, Pennsylvania, 18015

  • University of Alabama at Birmingham Comprehensive Cancer Center

    Birmingham, Alabama, 35294-3300

  • Ellis Fischel Cancer Center at University of Missouri - Columbia

    Columbia, Missouri, 65203

  • CCOP - Columbus

    Columbus, Ohio, 43206

  • Arthur G. James Cancer Hospital - Ohio State University

    Columbus, Ohio, 43210-1240

  • Mount Diablo Medical Center

    Concord, California, 94524-4110

  • CCOP - Dayton

    Dayton, Ohio, 45429

  • University of Colorado Cancer Center at University of Colorado Health Sciences Center

    Denver, Colorado, 80010

  • Delaware County Memorial Hospital

    Drexel Hill, Pennsylvania, 19026

  • Veterans Affairs Medical Center - East Orange

    East Orange, New Jersey, 07019

  • CCOP - St. Vincent Hospital Cancer Center, Green Bay

    Green Bay, Wisconsin, 54301

  • St. Vincent Hospital

    Green Bay, Wisconsin, 54307-3508

  • Sutter Health Western Division Cancer Research Group

    Greenbrae, California, 94904

  • University of Texas - MD Anderson Cancer Center

    Houston, Texas, 77030-4009

  • Methodist Cancer Center at Methodist Hospital

    Indianapolis, Indiana, 46206-1367

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • CCOP - Southern Nevada Cancer Research Foundation

    Las Vegas, Nevada, 89106

  • Markey Cancer Center at University of Kentucky Chandler Medical Center

    Lexington, Kentucky, 40536-0293

  • Monmouth Medical Center

    Long Branch, New Jersey, 07740-6395

  • CCOP - North Shore University Hospital

    Manhasset, New York, 11030

  • Marquette General Hospital

    Marquette, Michigan, 49855

  • Baptist Hospital of Miami

    Miami, Florida, 33176-2197

  • South Jersey Regional Cancer Center

    Millville, New Jersey, 08332

  • St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Medical College of Wisconsin Cancer Center

    Milwaukee, Wisconsin, 53226

  • Ball Memorial Hospital Cancer Center

    Muncie, Indiana, 47303-3499

  • CCOP - Ochsner

    New Orleans, Louisiana, 70121

  • Herbert Irving Comprehensive Cancer Center at Columbia University

    New York, New York, 10032

  • Lutheran General Cancer Care Center

    Park Ridge, Illinois, 60068

  • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

    Philadelphia, Pennsylvania, 19107-5541

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Albert Einstein Cancer Center

    Philadelphia, Pennsylvania, 19141-3098

  • Foundation for Cancer Research and Education

    Phoenix, Arizona, 85013

  • Atlantic City Medical Center

    Pomona, New Jersey, 08240

  • All Saints Cancer Center at All Saints Healthcare

    Racine, Wisconsin, 53405

  • CCOP - Metro-Minnesota

    Saint Louis Park, Minnesota, 55416

  • LDS Hospital

    Salt Lake City, Utah, 84143

  • CCOP - Santa Rosa Memorial Hospital

    Santa Rosa, California, 95403

  • University Cancer Center at University of Washington Medical Center

    Seattle, Washington, 98195-6043

  • Dixie Regional Medical Center

    St. George, Utah, 84770

  • CCOP - Toledo Community Hospital

    Toledo, Ohio, 43623-3456

  • Fox Chase Cancer Center at St. Francis Medical Center

    Trenton, New Jersey, 08629

  • CCOP - MainLine Health

    Wynnewood, Pennsylvania, 19096

  • Wellspan Health - York Cancer Center

    York, Pennsylvania, 17403

Other trials in United States

Canada2 sites

  • Cancer Care Ontario-London Regional Cancer Centre

    London, Ontario, N6A 4L6

  • Saint John Regional Hospital

    Saint John, New Brunswick, E2L 4L2

Other trials in Canada

About this study

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

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.

Read the 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.

Conditions
Prostate Cancer
Being tested
bicalutamide, estramustine phosphate sodium, etoposide, flutamide, paclitaxel
Keywords
stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer, stage IV prostate cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bicalutamideDrug

    Also called Casodex

    Administered orally at a dose of one 50mg tablet per day. Begins 8 weeks prior to radiotherapy and continues throughout radiotherapy.

  • estramustine phosphate sodiumDrug

    280 mg three times a day for 14 days and repeated every 3 weeks for 4 cycles

  • etoposideDrug

    50 mg/m^2 in divided doses b.i.d. for 14 days and repeated every 3 weeks for 4 cycles

  • flutamideDrug

    Also called Eulexin

    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.

  • paclitaxelDrug

    135 mg/m^2 given as a 1-hour infusion (on day 2 of each cycle) and repeated every 3 weeks for 4 cycles

  • Luteinizing hormone releasing hormone [LHRH] agonistDrug

    Releasing hormone agonists (such as leuprolide, goserelin, buserelin, triptorelin) will be given for 4 months

  • Radiation therapyRadiation

    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.

  • warfarinDrug

    Also called Coumadin

    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

Study groups in NCT00004054
Study groupRoleWhat they receive
Hormones and RTExperimentalAndrogen 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).
Receives: Drug: bicalutamide; Drug: flutamide; Drug: Luteinizing hormone releasing hormone [LHRH] agonist; Radiation: Radiation therapy
Hormones and RT plus ChemotherapyExperimentalAS (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.
Receives: Drug: bicalutamide; Drug: estramustine phosphate sodium; Drug: etoposide; Drug: flutamide; Drug: paclitaxel; Radiation: Radiation therapy; Drug: warfarin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (5-year Rate Reported)

    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.

    Measured: 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.

Secondary outcomes (4)

  1. Rate of Biochemical Failure at 5 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.

    Measured: 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.

  2. Rate of Local Progression at 5 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.

    Measured: 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.

  3. Rate of Distant Metastasis at Five 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.

    Measured: 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.

  4. Disease-free Survival Rate at 5 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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startJan 2000
  3. Primary completionApr 2010
  4. Study completionNov 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
397 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00004054
Sponsor's protocol ID
RTOG-9902
Other IDs
CDR0000067250
Status last verified
Nov 2017
First submitted
10 Dec 1999
Last updated
22 Oct 2020
Data monitoring committee
Yes

Publications

  • Rosenthal SA, Bae K, Pienta KJ, Sobczak ML, Asbell SO, Rajan R, Kerlin KJ, Michalski JM, Sandler HM; Radiation Therapy Oncology Group Trial 9902. Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99-02. Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):672-8. doi: 10.1016/j.ijrobp.2008.05.020. Epub 2008 Nov 5.

    PubMed 18990504

  • Rosenthal SA, Hunt D, Sartor AO, Pienta KJ, Gomella L, Grignon D, Rajan R, Kerlin KJ, Jones CU, Dobelbower M, Shipley WU, Zeitzer K, Hamstra DA, Donavanik V, Rotman M, Hartford AC, Michalski J, Seider M, Kim H, Kuban DA, Moughan J, Sandler H. A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902. Int J Radiat Oncol Biol Phys. 2015 Oct 1;93(2):294-302. doi: 10.1016/j.ijrobp.2015.05.024. Epub 2015 Jul 21.

    PubMed 26209502

  • Nguyen PL, Huang HR, Spratt DE, Davicioni E, Sandler HM, Shipley WU, Efstathiou JA, Simko JP, Pollack A, Dicker AP, Roach M, Rosenthal SA, Zeitzer KL, Mendez LC, Hartford AC, Hall WA, Desai AB, Rabinovitch RA, Peters CA, Rodgers JP, Tran P, Feng FY. Analysis of a Biopsy-Based Genomic Classifier in High-Risk Prostate Cancer: Meta-Analysis of the NRG Oncology/Radiation Therapy Oncology Group 9202, 9413, and 9902 Phase 3 Randomized Trials. Int J Radiat Oncol Biol Phys. 2023 Jul 1;116(3):521-529. doi: 10.1016/j.ijrobp.2022.12.035. Epub 2022 Dec 31.

    PubMed 36596347

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing bicalutamide, estramustine phosphate sodium and etoposide in people with Prostate Cancer, run by Radiation Therapy Oncology Group at 54 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00004054, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020; AzTrials last refreshed its copy on 6 Nov 2026.

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