Clinical trial NCT00030654: Hormone Therapy Plus Chemotherapy in Treating Patients With Prostate Cancer
Official title: A Phase III Randomized Study of Patients With High Risk, Hormone-Naive Prostate Cancer: Androgen Blockade With 4 Cycles of Immediate Chemotherapy Versus Androgen Blockade With Delayed Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer
recurrent prostate cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Eastern Cooperative Oncology Group
name: Cancer and Leukemia Group B
name: SWOG Cancer Research Network
name: NRG Oncology
First posted: 2003-01-27
Enrollment: 21
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as luteinizing hormone-releasing hormone agonist, flutamide, and bicalutamide may stop the adrenal glands from producing androgens. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with chemotherapy may kill more tumor cells. It is not yet known whether chemotherapy given at the same time as hormone therapy is more effective than chemotherapy given after hormone therapy in treating prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy given at the same time as hormone therapy with that of chemotherapy given after hormone therapy in treating patients who have prostate cancer.

Detailed description: OBJECTIVES:

Primary

* Compare the survival of patients with high-risk hormone-naive prostate cancer treated with androgen blockade with concurrent chemotherapy vs delayed chemotherapy.

Secondary

* Compare biochemical control in patients treated with these regimens.
* Determine the toxicity of these regimens in these patients.
* Compare the time to clinical failure, as measured by progression on bone scan or CT scan or a prostate-specific antigen (PSA) doubling time of ≤ 32 weeks, in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior therapy (surgery vs radiotherapy and/or brachytherapy vs both), original combined Gleason score (6 vs 7 vs 8-10), and prior vaccine therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive androgen blockade (AB) comprising a luteinizing-hormone releasing-hormone agonist continuously and oral flutamide or oral bicalutamide once daily for at least 1 month. Within 4 weeks of initiation of AB, patients begin chemotherapy. Patients receive 1, and only 1, of the following chemotherapy regimens:

  * Regimen A: Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV on day 3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  * Regimen B: Patients receive oral estramustine 3 times daily on days 1-5 and paclitaxel IV on days 3, 10, 17, 24, 31, and 38. Treatment repeats every 56 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  * Regimen C: Patients receive oral ketoconazole 3 times daily on days 1-7, 15-21, and 29-35; doxorubicin IV on days 1, 15, and 29; vinblastine IV on days 8, 22, and 36; and oral estramustine 3 times daily on days 8-14, 22-28, and 36-42. Treatment repeats every 56 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  * Regimen D: Patients receive oral estramustine 3 times daily on days 1-4 and docetaxel IV over 1 hour on days 3, 10, and 17. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  * Regimen E: Patients receive docetaxel IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  * Regimen F: Patients receive docetaxel IV on days 1, 8, and 15. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  * Regimen G: With approval from the protocol chair, patients may receive a regimen that has been demonstrated in a published phase II study to have at least a 50% response rate as measured by PSA decrease from baseline over 2 measurements 28 days apart or a decrease in measurable soft tissue disease by 50% in 2 dimensions.
* Arm II: Patients receive AB as in arm I. Patients continue with AB until clinical failure, at which time patients receive chemotherapy as in arm I. Patients who have a response may continue to receive chemotherapy beyond 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 1,050 patients will be accrued for this study within 4-6 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of adenocarcinoma of the prostate

  * Failed local treatments (surgery and/or radiotherapy and/or brachytherapy) as defined by a rising prostate-specific antigen level of at least 2.0 ng/mL (confirmed by 2 measurements at least 2 weeks apart) and a doubling time of 32 weeks or less
  * No clinical or radiographic evidence of disease
  * Original Gleason score of at least 7 OR Gleason score of 6 with capsular penetration or positive seminal vesicles or lymph nodes
* No metastases

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Zubrod 0-1

Life expectancy:

* Not specified

Hematopoietic:

* Absolute granulocyte count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 10 g/dL
* No history of bleeding disorders that would contraindicate warfarin, including clotting factor defects

Hepatic:

* Bilirubin no greater than 1.5 mg/dL
* AST/ALT no greater than 1.5 times upper limit of normal

Renal:

* Creatinine no greater than 1.5 mg/dL
* Blood Urea Nitrogen (BUN) no greater than 1.2 times normal

Cardiovascular:

* No symptomatic heart disease
* No history of myocardial infarction
* No history of thromboembolic events (e.g., deep vein thrombosis, symptomatic cerebrovascular events, or pulmonary embolism)

Other:

* No other major medical or psychiatric illness that would preclude study entry
* No other prior or concurrent invasive malignancy within the past 5 years except superficial skin cancer
* No history of esophageal varices
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 6 weeks since prior vaccine therapy

Chemotherapy:

* At least 5 years since prior chemotherapy

Endocrine therapy:

* Prior adjuvant or neoadjuvant hormonal therapy of less than 8 months duration allowed
* At least 1 year since prior androgen therapy

Radiotherapy:

* See Disease Characteristics
* At least 5 years since prior radiotherapy to sites other than prostate

Surgery:

* See Disease Characteristics

Other:

* Concurrent warfarin allowed
* Concurrent bisphosphonate therapy initiated prior to or after randomization allowed

Primary outcomes:
measure: Overall Survival
timeFrame: From date of randomization to the date of death due to any cause
Secondary outcomes:
measure: Biochemical control
timeFrame: From date of randomization to the date of first PSA failure defined as a PSA doubling time <= 32 weeks
measure: Time to Clinical Failure
timeFrame: Time from study entry to positive scan or positive disease evaluation of the pelvis or chest or a PSA doubling time ≤ 32 weeks
measure: Frequency of non-hematologic (>= grade 3), hematologic (grade >=4) and fatal (grade 5) toxicities
timeFrame: From the beginning of treatment to 90 days post treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Foundation for Cancer Research and Education
state: Arizona
city: Tucson
country: United States
facility: Veterans Affairs Medical Center - Tucson
state: Arizona
city: Little Rock
country: United States
facility: Veterans Affairs Medical Center - Little Rock
state: Arkansas
city: Martinez
country: United States
facility: Veterans Affairs Outpatient Clinic - Martinez
state: California
city: Aurora
country: United States
facility: Medical Center of Aurora - South Campus
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Memorial Hospital Cancer Center
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - St. Luke's Medical Center
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - Denver Rose
state: Colorado
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Incorporated
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Hope Cancer Care Center at Longmont United Hospital
state: Colorado
city: Pueblo
country: United States
facility: St. Mary-Corwin Regional Medical Center
state: Colorado
city: Thornton
country: United States
facility: Rocky Mountain Cancer Centers - Thornton
state: Colorado
city: Gainesville
country: United States
facility: Shands Cancer Center at the University of Florida Health Science Center
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Panama City
country: United States
facility: Gulf Coast Cancer Treatment Center
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: Veterans Affairs Medical Center - Tampa (Haley)
state: Florida
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
state: Idaho
city: Hines
country: United States
facility: Veterans Affairs Medical Center - Hines
state: Illinois
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Dubuque
country: United States
facility: Wendt Regional Cancer Center at Finley Hospital
state: Iowa
city: Wichita
country: United States
facility: Veterans Affairs Medical Center - Wichita
state: Kansas
city: Lexington
country: United States
facility: Veterans Affairs Medical Center - Lexington
state: Kentucky
city: New Orleans
country: United States
facility: Veterans Affairs Medical Center - New Orleans
state: Louisiana
city: Shreveport
country: United States
facility: Veterans Affairs Medical Center - Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Veterans Affairs Medical Center - Detroit
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Jackson
country: United States
facility: Veterans Affairs Medical Center - Jackson
state: Mississippi
city: Springfield
country: United States
facility: Cancer Research for the Ozarks
state: Missouri
city: Papillion
country: United States
facility: Midlands Cancer Center at Midlands Community Hospital
state: Nebraska
city: Albuquerque
country: United States
facility: Veterans Affairs Medical Center - Albuquerque
state: New Mexico
city: Albuquerque
country: United States
facility: MBCCOP - University of New Mexico HSC
state: New Mexico
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: Rochester
country: United States
facility: Lipson Cancer and Blood Center at Rochester General Hospital
state: New York
city: Goldsboro
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Akron
country: United States
facility: Akron General's McDowell Cancer Center
state: Ohio
city: Akron
country: United States
facility: Akron City Hospital at Summa Health System
state: Ohio
city: Cincinnati
country: United States
facility: Veterans Affairs Medical Center - Cincinnati
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Salem
country: United States
facility: Cancer Care Center, Incorporated
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Portland
country: United States
facility: Veterans Affairs Medical Center - Portland
state: Oregon
city: Darby
country: United States
facility: Mercy Fitzgerald Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Scranton
country: United States
facility: Mercy Hospital Cancer Center - Scranton
state: Pennsylvania
city: Charleston
country: United States
facility: Veterans Affairs Medical Center - Charleston
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Chattanooga
country: United States
facility: Erlanger Cancer Center
state: Tennessee
city: Memphis
country: United States
facility: Veterans Affairs Medical Center - Memphis
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
state: Tennessee
city: Amarillo
country: United States
facility: Veterans Affairs Medical Center - Amarillo
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: San Antonio
country: United States
facility: Veterans Affairs Medical Center - San Antonio (Murphy)
state: Texas
city: Temple
country: United States
facility: Veterans Affairs Medical Center - Temple
state: Texas
city: Murray
country: United States
facility: Cottonwood Hospital Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: Veterans Affairs Medical Center - Salt Lake City
state: Utah
city: Seattle
country: United States
facility: Veterans Affairs Medical Center - Seattle
state: Washington
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Clinic Research Foundation
state: Wisconsin
city: Racine
country: United States
facility: All Saints Cancer Center at All Saints Healthcare
state: Wisconsin
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Lima
country: Peru
facility: Instituto de Enfermedades Neoplasicas
city: San Juan
country: Puerto Rico
facility: San Juan City Hospital
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Kenneth J. Pienta, MD, FACP
role: STUDY_CHAIR
affiliation: Fox Chase Cancer Center
name: Naomi S. Balzer-Haas, MD
role: STUDY_CHAIR
affiliation: University of Maryland Greenebaum Cancer Center
name: Arif Hussain, MD
role: STUDY_CHAIR
affiliation: Deaconess Medical Center, Spokane, Washington
name: Gregory P. Swanson, MD
role: STUDY_CHAIR
affiliation: University of California, Davis
name: Primo N. Lara, MD
role: STUDY_CHAIR
References:
citation: Sandler HM, Pienta KJ. Rationale for the Radiation Therapy Oncology Group Study RTOG P-0014. Rev Urol. 2003;5 Suppl 2(Suppl 2):S28-34.