Clinical trial NCT00004054: Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 397
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Overall Survival (5-year Rate Reported)
timeFrame: 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:
measure: Rate of Biochemical Failure at 5 Years
timeFrame: 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.
measure: Rate of Local Progression at 5 Years
timeFrame: 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.
measure: Rate of Distant Metastasis at Five Years
timeFrame: 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.
measure: Disease-free Survival Rate at 5 Years
timeFrame: 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.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: Foundation for Cancer Research and Education
state: Arizona
city: Concord
country: United States
facility: Mount Diablo Medical Center
state: California
city: Greenbrae
country: United States
facility: Sutter Health Western Division Cancer Research Group
state: California
city: Santa Rosa
country: United States
facility: CCOP - Santa Rosa Memorial Hospital
state: California
city: Denver
country: United States
facility: University of Colorado Cancer Center at University of Colorado Health Sciences Center
state: Colorado
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Park Ridge
country: United States
facility: Lutheran General Cancer Care Center
state: Illinois
city: Indianapolis
country: United States
facility: Methodist Cancer Center at Methodist Hospital
state: Indiana
city: Muncie
country: United States
facility: Ball Memorial Hospital Cancer Center
state: Indiana
city: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Oncology Center
state: Maryland
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center and Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Marquette
country: United States
facility: Marquette General Hospital
state: Michigan
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: East Orange
country: United States
facility: Veterans Affairs Medical Center - East Orange
state: New Jersey
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Millville
country: United States
facility: South Jersey Regional Cancer Center
state: New Jersey
city: Pomona
country: United States
facility: Atlantic City Medical Center
state: New Jersey
city: Trenton
country: United States
facility: Fox Chase Cancer Center at St. Francis Medical Center
state: New Jersey
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University
state: New York
city: Akron
country: United States
facility: Akron General Medical Center
state: Ohio
city: Akron
country: United States
facility: Akron City Hospital
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Allentown
country: United States
facility: John and Dorothy Morgan Cancer Center at Lehigh Valley Hospital
state: Pennsylvania
city: Bethlehem
country: United States
facility: St. Luke's Hospital Cancer Center
state: Pennsylvania
city: Drexel Hill
country: United States
facility: Delaware County Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: CCOP - MainLine Health
state: Pennsylvania
city: York
country: United States
facility: Wellspan Health - York Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Saint George
country: United States
facility: Dixie Regional Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: St. Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Racine
country: United States
facility: All Saints Cancer Center at All Saints Healthcare
state: Wisconsin
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Howard M. Sandler, MD
role: STUDY_CHAIR
References:
citation: 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.
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 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.