Chemotherapy With or Without Strontium-89 in Treating Patients With Prostate Cancer

Condition(s) targeted: Prostate Cancer

Intervention: docetaxel (Drug); doxorubicin hydrochloride (Drug); estramustine phosphate sodium (Drug); ketoconazole (Drug); prednisone (Drug); vinblastine (Drug); strontium chloride Sr 89 (Radiation)

Phase: Phase 3

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Shi-Ming Tu, MD, Study Chair, Affiliation: M.D. Anderson Cancer Center

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radioactive substances such as strontium-89 may relieve bone pain associated with prostate cancer. It is not yet known whether chemotherapy is more effective with or without strontium-89 in treating bone metastases.

PURPOSE: This randomized phase III trial is studying giving chemotherapy together with strontium-89 to see how well it works compared to chemotherapy alone in treating patients with prostate cancer that has spread to the bone.

Official title: A Prospective Randomized Phase III, Trial Comparing Consolidation Therapy With or Without Stronium-89 Following Induction Chemotherapy in Androgen-Independent Prostate Cancer

Study design: Treatment, Randomized, Active Control

Primary outcome: Overall survival

Detailed description: OBJECTIVES:

- Compare the effectiveness, in terms of overall survival, of consolidation therapy with

or without strontium chloride Sr 89 after induction chemotherapy in patients with androgen-independent prostate cancer.

OUTLINE: This is a randomized study. Patients are stratified according to type of induction chemotherapy (KAVE vs prednisone and docetaxel), number of bony metastases (no more than 20 vs more than 20), ECOG performance status (0-1 vs 2-3), and use of zoledronate (yes vs no).

- Induction therapy: Patients receive 1 of 2 induction therapy regimens.

- Regimen A (KAVE): Patients receive doxorubicin IV over 24 hours on day 1 and oral

ketoconazole three times daily on days 1-7 of weeks 1, 3, and 5. Patients receive vinblastine IV over 30 minutes on day 1 and oral estramustine three times daily on days 1-7 of weeks 2, 4, and 6. Patients receive no treatment on weeks 7 and 8. Treatment repeats every 8 weeks for at least 2 courses* in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients continue to receive oral ketoconazole three times daily until disease progression.

- Regimen B (prednisone and docetaxel): Patients receive oral prednisone twice daily on

days 1-21 (days 1-14 of course 5 only) and docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for at least 5 courses in the absence of disease progression or unacceptable toxicity.

- Consolidation therapy: Patients with a prostate-specific antigen (PSA) response

(at least 50% decline in PSA level from baseline at week 16 OR at least 2 PSA levels decreased at least 50% from baseline) are randomized to 1 of 2 consolidation treatment arms.

- Arm I: Patients receive doxorubicin IV over 24 hours once weekly for 6 weeks plus

strontium chloride Sr 89 IV once at the beginning of chemotherapy.

- Arm II: Patients receive doxorubicin as in arm I. Patients are followed every 4 weeks

until PSA progression and then every 3 months thereafter.

PROJECTED ACCRUAL: Approximately 480 patients (240 randomized) will be accrued for this study within 48 months.

Minimum age: N/A. Maximum age: N/A. Gender(s): Male.

Criteria:

DISEASE CHARACTERISTICS:

- Diagnosis of adenocarcinoma of the prostate

- No small cell carcinoma

- Androgen-independent

- No evidence of response after either of the following anti-androgen withdrawal

periods:

- Within 4 weeks for flutamide

- Within 6 weeks for bicalutamide or nilutamide

- Rising prostate-specific antigen (PSA) (at least 5 ng/mL) on at least 2 occasions at

least 1 week apart AND bone pain OR worsening bone scan with new lesions in less than 6 months

- Castrate testosterone level no greater than 50 ng/mL (must continue treatment to

maintain castrate levels)

- No symptomatic lymphadenopathy (scrotal or pedal edema) or significant local invasive

disease (hematuria)

- Osteoblastic metastases on bone scan or CT scan

- No predominant visceral metastases to liver, lungs, or brain

PATIENT CHARACTERISTICS:

Age:

- Any age

Performance status:

- Zubrod 0-3

Life expectancy:

- At least 12 weeks

Hematopoietic:

- WBC greater than 3,000/mm^3

- Absolute neutrophil count greater than 1,500/mm^3

- Platelet count greater than 100,000/mm^3

Hepatic:

- Bilirubin no greater than 2 times upper limit of normal (ULN)

- AST and ALT no greater than 2 times ULN

Renal:

- Not specified

Cardiovascular:

- No transient ischemic attack or myocardial infarction within the past 12 months

- No active angina or claudication sufficient to limit activity

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

Other:

- Fertile patients must use effective contraception

- No prior allergic reaction to compounds of similar biologic or chemical composition

to study drugs

- No other conditions (e. g., pernicious anemia) associated with achlorhydria

- No other active malignancy or malignancy that is likely to become active except

non-melanoma skin cancer

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study participation

- No other uncontrolled concurrent illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 4 weeks since prior immunotherapy and recovered

- Prior angiogenesis inhibitors and gene therapy allowed

Chemotherapy:

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and

recovered

- No prior doxorubicin or vinblastine for patients receiving induction chemotherapy

with KAVE (ketoconazole, doxorubicin, vinblastine, estramustine)

- No prior docetaxel for patients receiving induction chemotherapy with prednisone plus

docetaxel

Endocrine therapy:

- See Disease Characteristics

- Prior secondary hormonal agents (e. g., aminoglutethimide, diethylstilbestrol, or

estramustine) allowed

- Prior steroid therapy (e. g., dexamethasone, prednisone, or hydrocortisone) allowed

Radiotherapy:

- At least 4 weeks since prior radiotherapy and recovered

- No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium

Surgery:

- No prior vagotomy

Other:

- No more than 1 prior cytotoxic regimen

Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah, Georgia 31403-3089, United States; Recruiting
Clinical Trials Office - Curtis and Elizabeth Anderson Cancer, Phone: 912-350-8568

Northeast Georgia Medical Center, Gainesville, Georgia 30501, United States; Recruiting
Richard J. LoCicero, MD, Phone: 770-297-5700

Resurrection Medical Center, Chicago, Illinois 60631, United States; Recruiting
Christopher G. Rose, MD, Phone: 847-965-3200

Swedish-American Regional Cancer Center, Rockford, Illinois 61104-2315, United States; Recruiting
Clinical Trials Office - Swedish-American Regional Cancer Cent, Phone: 815-489-4413

Veterans Affairs Medical Center - Hines, Hines, Illinois 60141, United States; Recruiting
Nirmala Bhoopalam, MD, Phone: 708-202-2782

Genesis Regional Cancer Center at Genesis Medical Center, Davenport, Iowa 52803, United States; Recruiting
George Kovach, MD, Phone: 563-421-1960

Hematology Oncology Associates of the Quad Cities, Bettendorf, Iowa 52722, United States; Recruiting
Shobha R. Chitneni, MD, MBBS, Phone: 563-355-7733

Mercy Medical Center - Sioux City, Sioux City, Iowa 51104, United States; Recruiting
Donald B. Wender, MD, PhD, Phone: 712-252-0088

Siouxland Hematology-Oncology Associates, LLP, Sioux City, Iowa 51101, United States; Recruiting
Donald B. Wender, MD, PhD, Phone: 712-252-0088

St. Luke's Regional Medical Center, Sioux City, Iowa 51104, United States; Recruiting
Donald B. Wender, MD, PhD, Phone: 712-252-0088

University of Mississippi Cancer Clinic, Jackson, Mississippi 39216, United States; Recruiting
Ralph B. Vance, Phone: 601-984-5590

Big Sky Oncology, Great Falls, Montana 59405-5309, United States; Recruiting
Clinical Trail Office - Big Sky Oncology, Phone: 406-731-8217

Billings Clinic - Downtown, Billings, Montana 59107-7000, United States; Recruiting
Clinical Trials Office - Billings Clinic - Downtown, Phone: 800-996-2663, Email: research@billingsclinic.org

Bozeman Deaconess Cancer Center, Bozeman, Montana 59715, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

CCOP - Montana Cancer Consortium, Billings, Montana 59101, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Community Medical Center, Missoula, Montana 59801, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Glacier Oncology, PLLC, Kalispell, Montana 59901, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Great Falls Clinic - Main Facility, Great Falls, Montana 59405, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Guardian Oncology and Center for Wellness, Missoula, Montana 59804, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Hematology-Oncology Centers of the Northern Rockies - Billings, Billings, Montana 59101, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Kalispell Medical Oncology at KRMC, Kalispell, Montana 59901, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Kalispell Regional Medical Center, Kalispell, Montana 59901, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Great Falls, Montana 59405, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center, Missoula, Montana 59807, United States; Recruiting
Clinical Trials Office - Montana Cancer Center at St. Patrick, Phone: 406-329-7029

Montana Cancer Specialists at Montana Cancer Center, Missoula, Montana 59807-7877, United States; Recruiting
Clinical Trials Office - Montana Cancer Specialists at Montana, Phone: 406-238-6962

Northern Rockies Radiation Oncology Center, Billings, Montana 59101, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Sletten Cancer Institute at Benefis Healthcare, Great Falls, Montana 59405, United States; Recruiting
Grant W. Harrer, MD, FACP, CCTI, Phone: 406-731-8100

St. James Healthcare Cancer Care, Butte, Montana 59701, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

St. Peter's Hospital, Helena, Montana 59601, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

St. Vincent Healthcare Cancer Care Services, Billings, Montana 59101, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Good Samaritan Cancer Center at Good Samaritan Hospital, Kearney, Nebraska 68848-1990, United States; Recruiting
Clinical Trials Office - Good Samaritan Cancer Center at Good, Phone: 308-865-7963

Kinston Medical Specialists, Kinston, North Carolina 28501, United States; Recruiting
Peter R. Watson, MD, Phone: 252-559-2200ext.201

Southeastern Medical Oncology Center - Goldsboro, Goldsboro, North Carolina 27534, United States; Recruiting
James N. Atkins, MD, Phone: 919-580-0000

Wayne Memorial Hospital, Incorporated, Goldsboro, North Carolina 27534, United States; Recruiting
James N. Atkins, MD, Phone: 919-580-0000

Barberton Citizens Hospital, Barberton, Ohio 44203, United States; Recruiting
William F. Demas, MD, Phone: 330-375-3557

Cancer Care Center, Incorporated, Salem, Ohio 44460, United States; Recruiting
William F. Demas, MD, Phone: 330-375-3557

Cancer Treatment Center, Wooster, Ohio 44691, United States; Recruiting
Clinical Trials Office - Cancer Treatment Center, Phone: 330-375-4221

Summa Center for Cancer Care at Akron City Hospital, Akron, Ohio 44309-2090, United States; Recruiting
Clinical Trials Office - Akron City Hospital, Phone: 330-375-6101

CCOP - Greenville, Greenville, South Carolina 29615, United States; Recruiting
Jeffrey K. Giguere, MD, FACP, Phone: 864-987-7000

McLeod Regional Medical Center, Florence, South Carolina 29501, United States; Recruiting
Clinical Trials Office - McLeod Regional Medical Center, Phone: 843-679-7256

M. D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States; Recruiting
Clinical Trials Office - M. D. Anderson Cancer Center at the U, Phone: 713-792-3245

Medical City Dallas Hospital, Dallas, Texas 75230, United States; Recruiting
Barry C. Mirtsching, MD, Phone: 972-566-5588

Welch Cancer Center at Sheridan Memorial Hospital, Sheridan, Wyoming 82801, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-238-6290

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: October 2001
Last updated: October 16, 2009