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); Dexamethasone (Drug)

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

Overall contact:
Shi-Ming Tu, MD, Phone: 713-792-2830

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 Strontium-89 Following Induction Chemotherapy in Androgen-Independent Prostate Cancer

Study design: Allocation: Randomized, Control: Active Control, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

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

Criteria:

Inclusion Criteria:

1. Rising PSA on at least 2 occasions >1 week apart (minimum value of 5 ng/ml), accompanied either by bone pain or, if the patient is asymptomatic, by a worsening bone scan with new lesions over a period of <6 months

2. Patients on antiandrogens should be discontinued from flutamide or nilutamide for at least 4 weeks and bicalutamide for 6 weeks; If progression is documented during this time interval as in inclusion criterion # 1, patients are eligible

3. Osteoblastic metastases on bone scan or CT scan

4. Androgen-independent prostate adenocarcinoma

5. Castrate testosterone level 6. >/= 18 years of age

7. Life expectancy of greater than or equal to 12 weeks

8. Zubrod performance status 9. Patients must have normal organ and marrow function as defined below: Leukocytes greater than 3,000/mcL Absolute neutrophil count greater than 1,500/mcL Platelets greater than 100,000/mcL Total bilirubin less than or equal to 2X institutional upper limit of normal AST(SGOT)/ALT(SGPT) less than or equal to 2X institutional upper limit of normal

10. The patient must have the ability to understand and the willingness to sign a written informed consent document

11. Participating subjects and their female partners agree to the use of adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation

Exclusion Criteria:

1. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used on this trial

2. Prior doxorubicin, or vinblastine in the KAVE arm and prior docetaxel in the prednisone plus docetaxel arm. However, previous treatment using other secondary hormonal agents (aminoglutimide, diethylstiphosterol, estramustine), steroids (dexamethasone, prednisone, hydrocortisone), angiogenesis inhibitors, gene therapy, or immunotherapy are allowed

3. More than one prior cytotoxic treatment

4. Prior Sr-89 or Sm-153 treatment

5. Patients who have had chemotherapy, immunotherapy, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

6. Previous vagotomy or other conditions (such as pernicious anemia) associated with achlorhydria. Patients with active peptic ulcer disease who still require regular use of H2 blockers (such as cimetidine [Tagamet], ranitidine [Zantac], famotidine [Pepcid], etc), proton pump inhibitors (omeprazole [Prilosec]), or antacids (Mylanta, Maalox, Tums, etc) at week 16 of induction chemotherapy (option 1 only) might not be suitable for randomization

7. Predominant visceral metastases in the liver, lungs, or brain

8. Symptomatic lymphadenopathy (scrotal or pedal edema) or significant local invasive disease (hematuria)

9. Small cell carcinoma

10. Recent history of transient ischemic attacks (TIA) or myocardial infarctions (MI) within 12 months, or active angina or claudication sufficient to limit activity

11. Active or likely to become active second malignancy (other than non-melanoma skin cancer)

12. Uncontrolled inter-current illness: including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Shi-Ming Tu, MD, Phone: 713-792-2830

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

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

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

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

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

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

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

Hematology-Oncology Centers of the Northern Rockies - Billings, Billings, Montana 59101, 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

Northern Rockies Radiation Oncology Center, Billings, Montana 59101, 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

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

St. James Healthcare Cancer Care, Butte, Montana 59701, 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

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

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

Great Falls, Montana 59405, 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

Kalispell Medical Oncology at KRMC, Kalispell, Montana 59901, 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

Kalispell Regional Medical Center, Kalispell, Montana 59901, 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

Guardian Oncology and Center for Wellness, Missoula, Montana 59804, 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

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: 252-559-2200, Ext: 201

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

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

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

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

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

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

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

UT MD Anderson Cancer Center Website

Starting date: October 2001
Last updated: August 20, 2010