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

NCT00004054 | Completed Phase 3 Results DMC

• 2 other identifiers: RTOG-9902CDR0000067250
• Study Type: interventional
• Target: 397
• Locations: 2 countries
• Sites: 54

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.

Conditions

Prostate Cancer

Keywords

stage IIB prostate cancer; stage IIA prostate cancer; stage III prostate cancer; stage IV prostate cancer

Outcome Measures

Primary Outcomes (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.

  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)

• Rate of Biochemical Failure at 5 Years

  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.

• Rate of Local Progression at 5 Years

  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.

• Rate of Distant Metastasis at Five Years

  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 Rate at 5 Years

  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.

Study Arms (2)

Hormones and RT

EXPERIMENTAL

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; Drug: flutamide; Drug: Luteinizing hormone releasing hormone [LHRH] agonist; Radiation: Radiation therapy

Hormones and RT plus Chemotherapy

EXPERIMENTAL

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; Drug: estramustine phosphate sodium; Drug: etoposide; Drug: flutamide; Drug: paclitaxel; Radiation: Radiation therapy; Drug: warfarin

Interventions

bicalutamide DRUG

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

Also known as: Casodex

Hormones and RT; Hormones and RT plus Chemotherapy

estramustine phosphate sodium DRUG

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

Hormones and RT plus Chemotherapy

etoposide DRUG

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

Hormones and RT plus Chemotherapy

flutamide 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.

Also known as: Eulexin

Hormones and RT; Hormones and RT plus Chemotherapy

paclitaxel 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

Hormones and RT plus Chemotherapy

Luteinizing hormone releasing hormone [LHRH] agonist DRUG

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

Hormones and RT

Radiation therapy 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; Hormones and RT plus Chemotherapy

warfarin 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

Also known as: Coumadin

Hormones and RT plus Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (54)

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35294-3300, United States

Location

Foundation for Cancer Research and Education

Phoenix, Arizona, 85013, United States

Location

Mount Diablo Medical Center

Concord, California, 94524-4110, United States

Location

Sutter Health Western Division Cancer Research Group

Greenbrae, California, 94904, United States

Location

CCOP - Santa Rosa Memorial Hospital

Santa Rosa, California, 95403, United States

Location

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

Denver, Colorado, 80010, United States

Location

Baptist Hospital of Miami

Miami, Florida, 33176-2197, United States

Location

Lutheran General Cancer Care Center

Park Ridge, Illinois, 60068, United States

Location

Methodist Cancer Center at Methodist Hospital

Indianapolis, Indiana, 46206-1367, United States

Location

Ball Memorial Hospital Cancer Center

Muncie, Indiana, 47303-3499, United States

Location

Markey Cancer Center at University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536-0293, United States

Location

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809, United States

Location

CCOP - Ochsner

New Orleans, Louisiana, 70121, United States

Location

Anne Arundel Oncology Center

Annapolis, Maryland, 21401, United States

Location

Greater Baltimore Medical Center and Cancer Center

Baltimore, Maryland, 21204, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0010, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Marquette General Hospital

Marquette, Michigan, 49855, United States

Location

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, 65203, United States

Location

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

Veterans Affairs Medical Center - East Orange

East Orange, New Jersey, 07019, United States

Location

Monmouth Medical Center

Long Branch, New Jersey, 07740-6395, United States

Location

South Jersey Regional Cancer Center

Millville, New Jersey, 08332, United States

Location

Atlantic City Medical Center

Pomona, New Jersey, 08240, United States

Location

Fox Chase Cancer Center at St. Francis Medical Center

Trenton, New Jersey, 08629, United States

Location

CCOP - North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, 10032, United States

Location

Akron General Medical Center

Akron, Ohio, 44302, United States

Location

Akron City Hospital

Akron, Ohio, 44304, United States

Location

CCOP - Columbus

Columbus, Ohio, 43206, United States

Location

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, 43210-1240, United States

Location

CCOP - Dayton

Dayton, Ohio, 45429, United States

Location

CCOP - Toledo Community Hospital

Toledo, Ohio, 43623-3456, United States

Location

John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital

Allentown, Pennsylvania, 18105, United States

Location

St. Luke's Hospital Cancer Center

Bethlehem, Pennsylvania, 18015, United States

Location

Delaware County Memorial Hospital

Drexel Hill, Pennsylvania, 19026, United States

Location

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, 19107-5541, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Albert Einstein Cancer Center

Philadelphia, Pennsylvania, 19141-3098, United States

Location

CCOP - MainLine Health

Wynnewood, Pennsylvania, 19096, United States

Location

Wellspan Health - York Cancer Center

York, Pennsylvania, 17403, United States

Location

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

Dixie Regional Medical Center

St. George, Utah, 84770, United States

Location

University Cancer Center at University of Washington Medical Center

Seattle, Washington, 98195-6043, United States

Location

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, 54301, United States

Location

St. Vincent Hospital

Green Bay, Wisconsin, 54307-3508, United States

Location

Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601, United States

Location

St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

All Saints Cancer Center at All Saints Healthcare

Racine, Wisconsin, 53405, United States

Location

Saint John Regional Hospital

Saint John, New Brunswick, E2L 4L2, Canada

Location

Cancer Care Ontario-London Regional Cancer Centre

London, Ontario, N6A 4L6, Canada

Location

Related Publications (3)

• 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.

  PMID: 18990504 RESULT

• 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.

  PMID: 26209502 RESULT

• 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.

  PMID: 36596347 DERIVED

Related Links

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

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

bicalutamide; Estramustine; Etoposide; Flutamide; Paclitaxel; Gonadotropin-Releasing Hormone; Radiotherapy; Warfarin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Glucosides; Glycosides; Carbohydrates; Anilides; Amides; Aniline Compounds; Amines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Therapeutics; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

wseiferheld@nrgoncology.org

Study Officials

• Howard M. Sandler, MD

  University of Michigan Rogel Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 1999
• First Posted: January 27, 2003
• Study Start: January 1, 2000
• Primary Completion: April 1, 2010
• Study Completion: November 1, 2013
• Last Updated: October 22, 2020
• Results First Posted: January 7, 2015

Record last verified: 2017-11

Locations

CA (2); US (52)