Chemotherapy With or Without Strontium-89 in Treating Patients With Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT00024167
- Lead Sponsor
- M.D. Anderson Cancer Center
- Brief Summary
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.
- 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), Eastern Cooperative Oncology (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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Male
- Target Recruitment
- 265
- 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
- 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
- Osteoblastic metastases on bone scan or CT scan
- Androgen-independent prostate adenocarcinoma
- Castrate testosterone level </= 50 ng/ml; treatment to maintain castrate levels of testosterone must be continued
- >/= 18 years of age
- Life expectancy of greater than or equal to 12 weeks
- Zubrod performance status </= 3
- 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
- The patient must have the ability to understand and the willingness to sign a written informed consent document
- 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
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used on this trial
- 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 (aminoglutethimide, diethylstilbesterol, estramustine), steroids (dexamethasone, prednisone, hydrocortisone), angiogenesis inhibitors, gene therapy, or immunotherapy are allowed
- More than one prior cytotoxic treatment
- Prior Sr-89 or Sm-153 treatment
- 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
- 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
- Predominant visceral metastases in the liver, lungs, or brain
- Symptomatic lymphadenopathy (scrotal or pedal edema) or significant local invasive disease (hematuria)
- Small cell carcinoma
- Recent history of transient ischemic attacks (TIA) or myocardial infarctions (MI) within 12 months, or active angina or claudication sufficient to limit activity
- Active or likely to become active second malignancy (other than non-melanoma skin cancer)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Induction regimen A Vinblastine Doxorubicin IV over 24 hours day 1; Oral ketoconazole 3 x daily on days 1-7 of weeks 1, 3, and 5; Vinblastine IV over 30 minutes Day 1, oral Estramustine 3 x daily on Days 1-7 of weeks 2, 4, and 6. Consolidation arm I Strontium chloride Sr 89 Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy. Induction regimen A Estramustine phosphate sodium Doxorubicin IV over 24 hours day 1; Oral ketoconazole 3 x daily on days 1-7 of weeks 1, 3, and 5; Vinblastine IV over 30 minutes Day 1, oral Estramustine 3 x daily on Days 1-7 of weeks 2, 4, and 6. Induction regimen A Doxorubicin hydrochloride Doxorubicin IV over 24 hours day 1; Oral ketoconazole 3 x daily on days 1-7 of weeks 1, 3, and 5; Vinblastine IV over 30 minutes Day 1, oral Estramustine 3 x daily on Days 1-7 of weeks 2, 4, and 6. Induction regimen A Ketoconazole Doxorubicin IV over 24 hours day 1; Oral ketoconazole 3 x daily on days 1-7 of weeks 1, 3, and 5; Vinblastine IV over 30 minutes Day 1, oral Estramustine 3 x daily on Days 1-7 of weeks 2, 4, and 6. Induction regimen B Docetaxel Oral Prednisone 2 x daily on days 1-21 (days 1-14 of course 5 only) and Docetaxel IV over 1 hour Day 1. Induction regimen B Dexamethasone Oral Prednisone 2 x daily on days 1-21 (days 1-14 of course 5 only) and Docetaxel IV over 1 hour Day 1. Induction regimen B Prednisone Oral Prednisone 2 x daily on days 1-21 (days 1-14 of course 5 only) and Docetaxel IV over 1 hour Day 1. Consolidation arm I Doxorubicin hydrochloride Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy. Consolidation arm II Doxorubicin hydrochloride Doxorubicin as in Consolidation arm I.
- Primary Outcome Measures
Name Time Method Overall Survival From Randomization Followed every 4 weeks from randomization until death, up to 7 years. Overall survival (OS) was computed using the number of months from the date of randomization to the date of death. Participants still alive were censored at the last follow-up date. Kaplan-Meier methodology was used to evaluate OS.
- Secondary Outcome Measures
Name Time Method Overall Survival From Registration Followed every 4 weeks from registration until death, up to 7 years. Overall survival (OS) was computed using the number of months from the date of registration to the date of death. Participants still alive were censored at the last follow-up date. Kaplan-Meier methodology was used to evaluate OS.
Trial Locations
- Locations (39)
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
St. Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
University of Mississippi Cancer Clinic
🇺🇸Jackson, Mississippi, United States
St. James Healthcare Cancer Care
🇺🇸Butte, Montana, United States
Big Sky Oncology
🇺🇸Great Falls, Montana, United States
Kalispell Medical Oncology at KRMC
🇺🇸Kalispell, Montana, United States
Guardian Oncology and Center for Wellness
🇺🇸Missoula, Montana, United States
Montana Cancer Specialists at Montana Cancer Center
🇺🇸Missoula, Montana, United States
Summa Center for Cancer Care at Akron City Hospital
🇺🇸Akron, Ohio, United States
Cancer Care Center, Incorporated
🇺🇸Salem, Ohio, United States
Northern Rockies Radiation Oncology Center
🇺🇸Billings, Montana, United States
Bozeman Deaconess Cancer Center
🇺🇸Bozeman, Montana, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Billings Clinic - Downtown
🇺🇸Billings, Montana, United States
Mercy Medical Center - Sioux City
🇺🇸Sioux City, Iowa, United States
Veterans Affairs Medical Center - Hines
🇺🇸Hines, Illinois, United States
Northeast Georgia Medical Center
🇺🇸Gainesville, Georgia, United States
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Swedish-American Regional Cancer Center
🇺🇸Rockford, Illinois, United States
Hematology Oncology Associates of the Quad Cities
🇺🇸Bettendorf, Iowa, United States
Barberton Citizens Hospital
🇺🇸Barberton, Ohio, United States
McLeod Regional Medical Center
🇺🇸Florence, South Carolina, United States
Genesis Regional Cancer Center at Genesis Medical Center
🇺🇸Davenport, Iowa, United States
CCOP - Montana Cancer Consortium
🇺🇸Billings, Montana, United States
Hematology-Oncology Centers of the Northern Rockies - Billings
🇺🇸Billings, Montana, United States
St. Vincent Healthcare Cancer Care Services
🇺🇸Billings, Montana, United States
Glacier Oncology, PLLC
🇺🇸Kalispell, Montana, United States
Great Falls Clinic - Main Facility
🇺🇸Great Falls, Montana, United States
St. Peter's Hospital
🇺🇸Helena, Montana, United States
Sletten Cancer Institute at Benefis Healthcare
🇺🇸Great Falls, Montana, United States
Good Samaritan Cancer Center at Good Samaritan Hospital
🇺🇸Kearney, Nebraska, United States
Kalispell Regional Medical Center
🇺🇸Kalispell, Montana, United States
Community Medical Center
🇺🇸Missoula, Montana, United States
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
🇺🇸Missoula, Montana, United States
Kinston Medical Specialists
🇺🇸Kinston, North Carolina, United States
Cancer Treatment Center
🇺🇸Wooster, Ohio, United States
Welch Cancer Center at Sheridan Memorial Hospital
🇺🇸Sheridan, Wyoming, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
CCOP - Greenville
🇺🇸Greenville, South Carolina, United States