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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004054
• Other study ID #: RTOG-9902
• Secondary ID: CDR0000067250
• Status: Completed
• Phase: Phase 3
• Start date: January 2000
• Est. completion date: November 2013

Study information

• Verified date: November 2017
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 397
• Est. completion date: November 2013
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• bicalutamide
Administered orally at a dose of one 50mg tablet per day. Begins 8 weeks prior to radiotherapy and continues throughout radiotherapy.
• estramustine phosphate sodium
280 mg three times a day for 14 days and repeated every 3 weeks for 4 cycles
• etoposide
50 mg/m^2 in divided doses b.i.d. for 14 days and repeated every 3 weeks for 4 cycles
• 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.
• 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
• 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.

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

Locations

Country	Name	City	State
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	Saint John Regional Hospital	Saint John	New Brunswick
United States	Akron City Hospital	Akron	Ohio
United States	Akron General Medical Center	Akron	Ohio
United States	John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital	Allentown	Pennsylvania
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Anne Arundel Oncology Center	Annapolis	Maryland
United States	Greater Baltimore Medical Center and Cancer Center	Baltimore	Maryland
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	St. Luke's Hospital Cancer Center	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Mount Diablo Medical Center	Concord	California
United States	CCOP - Dayton	Dayton	Ohio
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Denver	Colorado
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	Marquette General Hospital	Marquette	Michigan
United States	Baptist Hospital of Miami	Miami	Florida
United States	South Jersey Regional Cancer Center	Millville	New Jersey
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Ball Memorial Hospital Cancer Center	Muncie	Indiana
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Foundation for Cancer Research and Education	Phoenix	Arizona
United States	Atlantic City Medical Center	Pomona	New Jersey
United States	All Saints Cancer Center at All Saints Healthcare	Racine	Wisconsin
United States	Dixie Regional Medical Center	Saint George	Utah
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	LDS Hospital	Salt Lake City	Utah
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Fox Chase Cancer Center at St. Francis Medical Center	Trenton	New Jersey
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania
United States	Wellspan Health - York Cancer Center	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

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 etoposid — View Citation

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 Tr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.

External Links

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