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Hormone Therapy Plus Chemotherapy in Treating Patients With Prostate Cancer

Sponsor
Radiation Therapy Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT00030654
Collaborator
National Cancer Institute (NCI) (NIH), Eastern Cooperative Oncology Group (Other), Cancer and Leukemia Group B (Other), Southwest Oncology Group (Other), NRG Oncology (Other)
21
Enrollment
78
Locations
2
Arms
28.2
Duration (Months)
0.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date :
Oct 1, 2002
Actual Primary Completion Date :
Feb 4, 2005
Actual Study Completion Date :
Feb 4, 2005

Arms and Interventions

Arm Intervention/Treatment
Experimental: Androgen blockade + immediate chemotherapy

Androgen blockade with immediate chemotherapy

Drug: bicalutamide

Drug: docetaxel

Drug: doxorubicin hydrochloride

Drug: estramustine phosphate sodium

Drug: flutamide

Drug: ketoconazole

Drug: paclitaxel

Drug: releasing hormone agonist therapy

Drug: vinblastine sulfate
Experimental: Androgen blockade + delayed chemotherapy

Androgen blockade with delayed chemotherapy

Drug: bicalutamide

Drug: docetaxel

Drug: doxorubicin hydrochloride

Drug: estramustine phosphate sodium

Drug: flutamide

Drug: ketoconazole

Drug: paclitaxel

Drug: releasing hormone agonist therapy

Drug: vinblastine sulfate

Outcome Measures

Primary Outcome Measures

  1. Overall Survival [From date of randomization to the date of death due to any cause]

Secondary Outcome Measures

  1. Biochemical control [From date of randomization to the date of first PSA failure defined as a PSA doubling time <= 32 weeks]

  2. 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]

  3. Frequency of non-hematologic (>= grade 3), hematologic (grade >=4) and fatal (grade 5) toxicities [From the beginning of treatment to 90 days post treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 120 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Foundation for Cancer Research and Education Phoenix Arizona United States 85013
2 Veterans Affairs Medical Center - Tucson Tucson Arizona United States 85723
3 Veterans Affairs Medical Center - Little Rock Little Rock Arkansas United States 72205
4 Veterans Affairs Outpatient Clinic - Martinez Martinez California United States 94553
5 Medical Center of Aurora - South Campus Aurora Colorado United States 80012-0000
6 Boulder Community Hospital Boulder Colorado United States 80301-9019
7 Memorial Hospital Cancer Center Colorado Springs Colorado United States 80909
8 Penrose Cancer Center at Penrose Hospital Colorado Springs Colorado United States 80933
9 Porter Adventist Hospital Denver Colorado United States 80210
10 St. Joseph Hospital Denver Colorado United States 80218-1191
11 Presbyterian - St. Luke's Medical Center Denver Colorado United States 80218
12 Rocky Mountain Cancer Centers - Denver Rose Denver Colorado United States 80220
13 CCOP - Colorado Cancer Research Program, Incorporated Denver Colorado United States 80224
14 Swedish Medical Center Englewood Colorado United States 80112
15 Sky Ridge Medical Center Lone Tree Colorado United States 80124
16 Hope Cancer Care Center at Longmont United Hospital Longmont Colorado United States 80501
17 St. Mary-Corwin Regional Medical Center Pueblo Colorado United States 81004
18 Rocky Mountain Cancer Centers - Thornton Thornton Colorado United States 80221
19 Shands Cancer Center at the University of Florida Health Science Center Gainesville Florida United States 32610-0385
20 University of Miami Sylvester Comprehensive Cancer Center Miami Florida United States 33136
21 Gulf Coast Cancer Treatment Center Panama City Florida United States 32405-4587
22 Tallahassee Memorial Hospital Tallahassee Florida United States 32308
23 Veterans Affairs Medical Center - Tampa (Haley) Tampa Florida United States 33612
24 Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center Boise Idaho United States 83706
25 Veterans Affairs Medical Center - Hines Hines Illinois United States 60141
26 John Stoddard Cancer Center at Iowa Methodist Medical Center Des Moines Iowa United States 50309
27 Mercy Cancer Center at Mercy Medical Center - Des Moines Des Moines Iowa United States 50314
28 John Stoddard Cancer Center at Iowa Lutheran Hospital Des Moines Iowa United States 50316-2301
29 Wendt Regional Cancer Center at Finley Hospital Dubuque Iowa United States 52001
30 Veterans Affairs Medical Center - Wichita Wichita Kansas United States 67218
31 Veterans Affairs Medical Center - Lexington Lexington Kentucky United States 40502-2236
32 Veterans Affairs Medical Center - New Orleans New Orleans Louisiana United States 70112
33 Veterans Affairs Medical Center - Shreveport Shreveport Louisiana United States 71101-4295
34 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland United States 21231
35 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109-0010
36 Veterans Affairs Medical Center - Detroit Detroit Michigan United States 48201-1932
37 West Michigan Cancer Center Kalamazoo Michigan United States 49007
38 Veterans Affairs Medical Center - Jackson Jackson Mississippi United States 39216
39 Cancer Research for the Ozarks Springfield Missouri United States 65807
40 Midlands Cancer Center at Midlands Community Hospital Papillion Nebraska United States 68128-4157
41 Veterans Affairs Medical Center - Albuquerque Albuquerque New Mexico United States 87108-5138
42 MBCCOP - University of New Mexico HSC Albuquerque New Mexico United States 87131
43 NYU School of Medicine's Kaplan Comprehensive Cancer Center New York New York United States 10016
44 Lipson Cancer and Blood Center at Rochester General Hospital Rochester New York United States 14621
45 CCOP - Southeast Cancer Control Consortium Goldsboro North Carolina United States 27534-9479
46 Akron General's McDowell Cancer Center Akron Ohio United States 44302
47 Akron City Hospital at Summa Health System Akron Ohio United States 44304
48 Veterans Affairs Medical Center - Cincinnati Cincinnati Ohio United States 45220-2288
49 Veterans Affairs Medical Center - Dayton Dayton Ohio United States 45428-1002
50 Cancer Care Center, Incorporated Salem Ohio United States 44460
51 Cancer Treatment Center Wooster Ohio United States 44691
52 Veterans Affairs Medical Center - Portland Portland Oregon United States 97207
53 Mercy Fitzgerald Hospital Darby Pennsylvania United States 19023
54 Penn State Cancer Institute at Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033-0850
55 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
56 Mercy Hospital Cancer Center - Scranton Scranton Pennsylvania United States 18501
57 Veterans Affairs Medical Center - Charleston Charleston South Carolina United States 29401-5799
58 CCOP - Greenville Greenville South Carolina United States 29615
59 Rapid City Regional Hospital Rapid City South Dakota United States 57709
60 Erlanger Cancer Center Chattanooga Tennessee United States 37403
61 Veterans Affairs Medical Center - Memphis Memphis Tennessee United States 38104
62 Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center Nashville Tennessee United States 37232-5671
63 Veterans Affairs Medical Center - Amarillo Amarillo Texas United States 79106
64 University of Texas Medical Branch Galveston Texas United States 77555-0209
65 Veterans Affairs Medical Center - San Antonio (Murphy) San Antonio Texas United States 78229
66 Veterans Affairs Medical Center - Temple Temple Texas United States 76504
67 Cottonwood Hospital Medical Center Murray Utah United States 84107
68 McKay-Dee Hospital Center Ogden Utah United States 84403
69 Utah Valley Regional Medical Center - Provo Provo Utah United States 84604
70 Dixie Regional Medical Center Saint George Utah United States 84770
71 Veterans Affairs Medical Center - Salt Lake City Salt Lake City Utah United States 84148
72 Veterans Affairs Medical Center - Seattle Seattle Washington United States 98108
73 CCOP - St. Vincent Hospital Cancer Center, Green Bay Green Bay Wisconsin United States 54301
74 CCOP - Marshfield Clinic Research Foundation Marshfield Wisconsin United States 54449
75 All Saints Cancer Center at All Saints Healthcare Racine Wisconsin United States 53405
76 Westmead Hospital Westmead New South Wales Australia 2145
77 Instituto de Enfermedades Neoplasicas Lima Peru 34
78 San Juan City Hospital San Juan Puerto Rico 00936-7344

Sponsors and Collaborators

  • Radiation Therapy Oncology Group
  • National Cancer Institute (NCI)
  • Eastern Cooperative Oncology Group
  • Cancer and Leukemia Group B
  • Southwest Oncology Group
  • NRG Oncology

Investigators

  • Study Chair: Kenneth J. Pienta, MD, FACP, University of Michigan Rogel Cancer Center
  • Study Chair: Naomi S. Balzer-Haas, MD, Fox Chase Cancer Center
  • Study Chair: Arif Hussain, MD, University of Maryland Greenebaum Cancer Center
  • Study Chair: Gregory P. Swanson, MD, Deaconess Medical Center, Spokane, Washington
  • Study Chair: Primo N. Lara, MD, University of California, Davis

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00030654
Other Study ID Numbers:
  • RTOG-P-0014
  • CDR0000069186
  • ECOG-RTOG-P-0014
  • CALGB-RTOG-P-0014
  • SWOG-RTOG-P-0014
First Posted:
Jan 27, 2003
Last Update Posted:
Oct 22, 2020
Last Verified:
Mar 1, 2017
Keywords provided by Radiation Therapy Oncology Group
adenocarcinoma of the prostate
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer
recurrent prostate cancer
Additional relevant MeSH terms:
Prostatic Neoplasms
Ketoconazole
Vinblastine
Docetaxel
Doxorubicin
Liposomal doxorubicin
Bicalutamide
Flutamide
Estramustine
Hormones

Study Results

No Results Posted as of Oct 22, 2020