Hormone Therapy Plus Chemotherapy in Treating Patients With Prostate Cancer

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00030654
• Other study ID #: RTOG-P-0014
• Secondary ID: CDR0000069186ECO
• Status: Completed
• Phase: Phase 3
• Start date: October 2002
• Est. completion date: February 4, 2005

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: February 4, 2005
• Est. primary completion date: February 4, 2005
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• bicalutamide

• docetaxel

• doxorubicin hydrochloride

• estramustine phosphate sodium

• flutamide

• ketoconazole

• paclitaxel

• releasing hormone agonist therapy

• vinblastine sulfate

Locations

Country	Name	City	State
Australia	Westmead Hospital	Westmead	New South Wales
Peru	Instituto de Enfermedades Neoplasicas	Lima
Puerto Rico	San Juan City Hospital	San Juan
United States	Akron City Hospital at Summa Health System	Akron	Ohio
United States	Akron General's McDowell Cancer Center	Akron	Ohio
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico
United States	Veterans Affairs Medical Center - Amarillo	Amarillo	Texas
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Medical Center of Aurora - South Campus	Aurora	Colorado
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Boulder Community Hospital	Boulder	Colorado
United States	Veterans Affairs Medical Center - Charleston	Charleston	South Carolina
United States	Erlanger Cancer Center	Chattanooga	Tennessee
United States	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio
United States	Memorial Hospital Cancer Center	Colorado Springs	Colorado
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Mercy Fitzgerald Hospital	Darby	Pennsylvania
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rocky Mountain Cancer Centers - Denver Rose	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Veterans Affairs Medical Center - Detroit	Detroit	Michigan
United States	Wendt Regional Cancer Center at Finley Hospital	Dubuque	Iowa
United States	Swedish Medical Center	Englewood	Colorado
United States	Shands Cancer Center at the University of Florida Health Science Center	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	CCOP - Greenville	Greenville	South Carolina
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Veterans Affairs Medical Center - Hines	Hines	Illinois
United States	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Little Rock	Little Rock	Arkansas
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California
United States	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Cottonwood Hospital Medical Center	Murray	Utah
United States	Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center	Nashville	Tennessee
United States	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Gulf Coast Cancer Treatment Center	Panama City	Florida
United States	Midlands Cancer Center at Midlands Community Hospital	Papillion	Nebraska
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Foundation for Cancer Research and Education	Phoenix	Arizona
United States	Veterans Affairs Medical Center - Portland	Portland	Oregon
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	St. Mary-Corwin Regional Medical Center	Pueblo	Colorado
United States	All Saints Cancer Center at All Saints Healthcare	Racine	Wisconsin
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Lipson Cancer and Blood Center at Rochester General Hospital	Rochester	New York
United States	Dixie Regional Medical Center	Saint George	Utah
United States	Cancer Care Center, Incorporated	Salem	Ohio
United States	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania
United States	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	Cancer Research for the Ozarks	Springfield	Missouri
United States	Tallahassee Memorial Hospital	Tallahassee	Florida
United States	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida
United States	Veterans Affairs Medical Center - Temple	Temple	Texas
United States	Rocky Mountain Cancer Centers - Thornton	Thornton	Colorado
United States	Veterans Affairs Medical Center - Tucson	Tucson	Arizona
United States	Veterans Affairs Medical Center - Wichita	Wichita	Kansas
United States	Cancer Treatment Center	Wooster	Ohio

Sponsors (6)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, National Cancer Institute (NCI), NRG Oncology, Southwest Oncology Group

Countries where clinical trial is conducted

United States,  Australia,  Peru,  Puerto Rico, 

References & Publications (1)

Sandler HM, Pienta KJ. Rationale for the Radiation Therapy Oncology Group Study RTOG P-0014. Rev Urol. 2003;5 Suppl 2:S28-34. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		From date of randomization to the date of death due to any cause
Secondary	Biochemical control		From date of randomization to the date of first PSA failure defined as a PSA doubling time <= 32 weeks
Secondary	Time to Clinical Failure		Time from study entry to positive scan or positive disease evaluation of the pelvis or chest or a PSA doubling time = 32 weeks
Secondary	Frequency of non-hematologic (>= grade 3), hematologic (grade >=4) and fatal (grade 5) toxicities		From the beginning of treatment to 90 days post treatment