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

NCT ID: NCT00004054

Last Updated: 2020-10-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

397 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-01-31

Study Completion Date

2013-11-30

Brief Summary

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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

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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

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Prostate Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

bicalutamide

Intervention Type DRUG

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

flutamide

Intervention Type DRUG

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.

Luteinizing hormone releasing hormone [LHRH] agonist

Intervention Type DRUG

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

Radiation therapy

Intervention Type RADIATION

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.

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.

Group Type EXPERIMENTAL

bicalutamide

Intervention Type DRUG

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

estramustine phosphate sodium

Intervention Type DRUG

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

etoposide

Intervention Type DRUG

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

flutamide

Intervention Type DRUG

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.

paclitaxel

Intervention Type DRUG

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 therapy

Intervention Type RADIATION

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.

warfarin

Intervention Type DRUG

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

Interventions

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bicalutamide

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

Intervention Type DRUG

estramustine phosphate sodium

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

Intervention Type DRUG

etoposide

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

Intervention Type 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.

Intervention Type 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

Intervention Type DRUG

Luteinizing hormone releasing hormone [LHRH] agonist

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

Intervention Type DRUG

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.

Intervention Type RADIATION

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

Intervention Type DRUG

Other Intervention Names

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Casodex Eulexin Coumadin

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Howard M. Sandler, MD

Role: STUDY_CHAIR

University of Michigan Rogel Cancer Center

Locations

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University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

Foundation for Cancer Research and Education

Phoenix, Arizona, United States

Site Status

Mount Diablo Medical Center

Concord, California, United States

Site Status

Sutter Health Western Division Cancer Research Group

Greenbrae, California, United States

Site Status

CCOP - Santa Rosa Memorial Hospital

Santa Rosa, California, United States

Site Status

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

Denver, Colorado, United States

Site Status

Baptist Hospital of Miami

Miami, Florida, United States

Site Status

Lutheran General Cancer Care Center

Park Ridge, Illinois, United States

Site Status

Methodist Cancer Center at Methodist Hospital

Indianapolis, Indiana, United States

Site Status

Ball Memorial Hospital Cancer Center

Muncie, Indiana, United States

Site Status

Markey Cancer Center at University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

Site Status

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States

Site Status

CCOP - Ochsner

New Orleans, Louisiana, United States

Site Status

Anne Arundel Oncology Center

Annapolis, Maryland, United States

Site Status

Greater Baltimore Medical Center and Cancer Center

Baltimore, Maryland, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status

Marquette General Hospital

Marquette, Michigan, United States

Site Status

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Site Status

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, United States

Site Status

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Veterans Affairs Medical Center - East Orange

East Orange, New Jersey, United States

Site Status

Monmouth Medical Center

Long Branch, New Jersey, United States

Site Status

South Jersey Regional Cancer Center

Millville, New Jersey, United States

Site Status

Atlantic City Medical Center

Pomona, New Jersey, United States

Site Status

Fox Chase Cancer Center at St. Francis Medical Center

Trenton, New Jersey, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, United States

Site Status

Akron General Medical Center

Akron, Ohio, United States

Site Status

Akron City Hospital

Akron, Ohio, United States

Site Status

CCOP - Columbus

Columbus, Ohio, United States

Site Status

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Site Status

CCOP - Dayton

Dayton, Ohio, United States

Site Status

CCOP - Toledo Community Hospital

Toledo, Ohio, United States

Site Status

John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital

Allentown, Pennsylvania, United States

Site Status

St. Luke's Hospital Cancer Center

Bethlehem, Pennsylvania, United States

Site Status

Delaware County Memorial Hospital

Drexel Hill, Pennsylvania, United States

Site Status

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Albert Einstein Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

CCOP - MainLine Health

Wynnewood, Pennsylvania, United States

Site Status

Wellspan Health - York Cancer Center

York, Pennsylvania, United States

Site Status

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

LDS Hospital

Salt Lake City, Utah, United States

Site Status

Dixie Regional Medical Center

St. George, Utah, United States

Site Status

University Cancer Center at University of Washington Medical Center

Seattle, Washington, United States

Site Status

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, United States

Site Status

St. Vincent Hospital

Green Bay, Wisconsin, United States

Site Status

Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States

Site Status

St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Site Status

All Saints Cancer Center at All Saints Healthcare

Racine, Wisconsin, United States

Site Status

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Site Status

Cancer Care Ontario-London Regional Cancer Centre

London, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type RESULT
PMID: 18990504 (View on PubMed)

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.

Reference Type RESULT
PMID: 26209502 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36596347 (View on PubMed)

Related Links

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https://nctn-data-archive.nci.nih.gov/

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Other Identifiers

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CDR0000067250

Identifier Type: -

Identifier Source: secondary_id

RTOG-9902

Identifier Type: -

Identifier Source: org_study_id

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