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

NCT ID: NCT00024167

Last Updated: 2016-03-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 265 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-04-30

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Induction regimen A

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.

Group Type: EXPERIMENTAL

Doxorubicin hydrochloride

Intervention Type: DRUG

20 mg/m2 IV, day 1 on Weeks 1, 3, 5

Estramustine phosphate sodium

Intervention Type: DRUG

140 mg orally 3 x day, Days 1 through 7 on Weeks 2, 4, 6

Ketoconazole

Intervention Type: DRUG

400 mg orally (po) 3 x day, Days 1 through 7

Vinblastine

Intervention Type: DRUG

4 mg/m2 IVPB, Day 1 on Weeks 2, 4, 6

Induction regimen B

Oral Prednisone 2 x daily on days 1-21 (days 1-14 of course 5 only) and Docetaxel IV over 1 hour Day 1.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

75 mg/m2 intravenous piggyback (IVPB) over 1 hour, Day 1, every 3 weeks.

Prednisone

Intervention Type: DRUG

5 mg orally 2 x daily, weeks 1-14

Dexamethasone

Intervention Type: DRUG

4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel.

Consolidation arm I

Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy.

Group Type: EXPERIMENTAL

Doxorubicin hydrochloride

Intervention Type: DRUG

20 mg/m2 IV, day 1 on Weeks 1, 3, 5

Strontium chloride Sr 89

Intervention Type: RADIATION

One dose (4 mCi total dose) IV

Consolidation arm II

Doxorubicin as in Consolidation arm I.

Group Type: EXPERIMENTAL

Doxorubicin hydrochloride

Intervention Type: DRUG

20 mg/m2 IV, day 1 on Weeks 1, 3, 5

Interventions

Docetaxel

75 mg/m2 intravenous piggyback (IVPB) over 1 hour, Day 1, every 3 weeks.

Intervention Type: DRUG

Doxorubicin hydrochloride

20 mg/m2 IV, day 1 on Weeks 1, 3, 5

Intervention Type: DRUG

Estramustine phosphate sodium

140 mg orally 3 x day, Days 1 through 7 on Weeks 2, 4, 6

Intervention Type: DRUG

Ketoconazole

400 mg orally (po) 3 x day, Days 1 through 7

Intervention Type: DRUG

Prednisone

5 mg orally 2 x daily, weeks 1-14

Intervention Type: DRUG

Vinblastine

4 mg/m2 IVPB, Day 1 on Weeks 2, 4, 6

Intervention Type: DRUG

Strontium chloride Sr 89

One dose (4 mCi total dose) IV

Intervention Type: RADIATION

Dexamethasone

4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel.

Intervention Type: DRUG

Other Intervention Names

Taxotere; Adriamycin PFS; Adriamycin RDF; Doxorubicin; Estramustine; Nizoral; Velban; strontium-89 chloride; Sr-89; strontium-89; Metastron; Decadron

Eligibility 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 </= 50 ng/ml; treatment to maintain castrate levels of testosterone must be continued

6. >/= 18 years of age

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

8. Zubrod performance status </= 3

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 (aminoglutethimide, diethylstilbesterol, 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shi-Ming Tu, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, United States

Veterans Affairs Medical Center - Hines

Hines, Illinois, United States

Swedish-American Regional Cancer Center

Rockford, Illinois, United States

Hematology Oncology Associates of the Quad Cities

Bettendorf, Iowa, United States

Genesis Regional Cancer Center at Genesis Medical Center

Davenport, Iowa, United States

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, United States

Mercy Medical Center - Sioux City

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

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, United States

Northern Rockies Radiation Oncology Center

Billings, Montana, United States

St. Vincent Healthcare Cancer Care Services

Billings, Montana, United States

Billings Clinic - Downtown

Billings, Montana, United States

Bozeman Deaconess Cancer Center

Bozeman, Montana, United States

St. James Healthcare Cancer Care

Butte, Montana, United States

Big Sky Oncology

Great Falls, Montana, United States

Great Falls Clinic - Main Facility

Great Falls, Montana, United States

Sletten Cancer Institute at Benefis Healthcare

Great Falls, Montana, United States

Great Falls, Montana, United States

St. Peter's Hospital

Helena, Montana, United States

Glacier Oncology, PLLC

Kalispell, Montana, United States

Kalispell Medical Oncology at KRMC

Kalispell, Montana, United States

Kalispell Regional Medical Center

Kalispell, Montana, United States

Community Medical Center

Missoula, Montana, United States

Guardian Oncology and Center for Wellness

Missoula, Montana, United States

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, United States

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

Missoula, Montana, United States

Good Samaritan Cancer Center at Good Samaritan Hospital

Kearney, Nebraska, United States

Kinston Medical Specialists

Kinston, North Carolina, United States

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States

Barberton Citizens Hospital

Barberton, Ohio, United States

Cancer Care Center, Incorporated

Salem, Ohio, United States

Cancer Treatment Center

Wooster, Ohio, United States

McLeod Regional Medical Center

Florence, South Carolina, United States

CCOP - Greenville

Greenville, South Carolina, United States

Medical City Dallas Hospital

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, United States

Countries

United States

References

Tu SM, Kim J, Pagliaro LC, Vakar-Lopez F, Wong FC, Wen S, General R, Podoloff DA, Lin SH, Logothetis CJ. Therapy tolerance in selected patients with androgen-independent prostate cancer following strontium-89 combined with chemotherapy. J Clin Oncol. 2005 Nov 1;23(31):7904-10. doi: 10.1200/JCO.2005.01.2310.

Reference Type: RESULT

PMID: 16258090 (View on PubMed)

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

U10CA045809

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA016672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MDA-ID-00156

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-3410

Identifier Type: -

Identifier Source: secondary_id

CDR0000068897

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2009-00009

Identifier Type: REGISTRY

Identifier Source: secondary_id

ID00-156

Identifier Type: -

Identifier Source: org_study_id