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

Primary Purpose

Prostate Cancer

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Docetaxel
Doxorubicin hydrochloride
Estramustine phosphate sodium
Ketoconazole
Prednisone
Vinblastine
Strontium chloride Sr 89
Dexamethasone
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer, Strontium-89, Induction Chemotherapy, Androgen-Independent Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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

Sites / Locations

  • Northeast Georgia Medical Center
  • Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Veterans Affairs Medical Center - Hines
  • Swedish-American Regional Cancer Center
  • Hematology Oncology Associates of the Quad Cities
  • Genesis Regional Cancer Center at Genesis Medical Center
  • Siouxland Hematology-Oncology Associates, LLP
  • Mercy Medical Center - Sioux City
  • St. Luke's Regional Medical Center
  • University of Mississippi Cancer Clinic
  • CCOP - Montana Cancer Consortium
  • Hematology-Oncology Centers of the Northern Rockies - Billings
  • Northern Rockies Radiation Oncology Center
  • St. Vincent Healthcare Cancer Care Services
  • Billings Clinic - Downtown
  • Bozeman Deaconess Cancer Center
  • St. James Healthcare Cancer Care
  • Big Sky Oncology
  • Great Falls Clinic - Main Facility
  • Sletten Cancer Institute at Benefis Healthcare
  • St. Peter's Hospital
  • Glacier Oncology, PLLC
  • Kalispell Medical Oncology at KRMC
  • Kalispell Regional Medical Center
  • Community Medical Center
  • Guardian Oncology and Center for Wellness
  • Montana Cancer Specialists at Montana Cancer Center
  • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • Good Samaritan Cancer Center at Good Samaritan Hospital
  • Kinston Medical Specialists
  • Summa Center for Cancer Care at Akron City Hospital
  • Barberton Citizens Hospital
  • Cancer Care Center, Incorporated
  • Cancer Treatment Center
  • McLeod Regional Medical Center
  • CCOP - Greenville
  • Medical City Dallas Hospital
  • University of Texas MD Anderson Cancer Center
  • Welch Cancer Center at Sheridan Memorial Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Induction regimen A

Induction regimen B

Consolidation arm I

Consolidation arm II

Arm Description

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.

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

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

Doxorubicin as in Consolidation arm I.

Outcomes

Primary Outcome Measures

Overall Survival From Randomization
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

Overall Survival From Registration
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.

Full Information

First Posted
September 13, 2001
Last Updated
February 19, 2016
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00024167
Brief Title
Chemotherapy With or Without Strontium-89 in Treating Patients With Prostate Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Terminated
Why Stopped
Terminated due to slow accrual
Study Start Date
April 2002 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer, Strontium-89, Induction Chemotherapy, Androgen-Independent Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
265 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Induction regimen A
Arm Type
Experimental
Arm Description
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.
Arm Title
Induction regimen B
Arm Type
Experimental
Arm Description
Oral Prednisone 2 x daily on days 1-21 (days 1-14 of course 5 only) and Docetaxel IV over 1 hour Day 1.
Arm Title
Consolidation arm I
Arm Type
Experimental
Arm Description
Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy.
Arm Title
Consolidation arm II
Arm Type
Experimental
Arm Description
Doxorubicin as in Consolidation arm I.
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
Taxotere
Intervention Description
75 mg/m2 intravenous piggyback (IVPB) over 1 hour, Day 1, every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin hydrochloride
Other Intervention Name(s)
Adriamycin PFS, Adriamycin RDF, Doxorubicin
Intervention Description
20 mg/m2 IV, day 1 on Weeks 1, 3, 5
Intervention Type
Drug
Intervention Name(s)
Estramustine phosphate sodium
Other Intervention Name(s)
Estramustine
Intervention Description
140 mg orally 3 x day, Days 1 through 7 on Weeks 2, 4, 6
Intervention Type
Drug
Intervention Name(s)
Ketoconazole
Other Intervention Name(s)
Nizoral
Intervention Description
400 mg orally (po) 3 x day, Days 1 through 7
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
5 mg orally 2 x daily, weeks 1-14
Intervention Type
Drug
Intervention Name(s)
Vinblastine
Other Intervention Name(s)
Velban
Intervention Description
4 mg/m2 IVPB, Day 1 on Weeks 2, 4, 6
Intervention Type
Radiation
Intervention Name(s)
Strontium chloride Sr 89
Other Intervention Name(s)
strontium-89 chloride, Sr-89, strontium-89, Metastron
Intervention Description
One dose (4 mCi total dose) IV
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Decadron
Intervention Description
4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel.
Primary Outcome Measure Information:
Title
Overall Survival From Randomization
Description
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.
Time Frame
Followed every 4 weeks from randomization until death, up to 7 years.
Secondary Outcome Measure Information:
Title
Overall Survival From Registration
Description
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.
Time Frame
Followed every 4 weeks from registration until death, up to 7 years.

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shi-Ming Tu, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Northeast Georgia Medical Center
City
Gainesville
State/Province
Georgia
ZIP/Postal Code
30501
Country
United States
Facility Name
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31403-3089
Country
United States
Facility Name
Veterans Affairs Medical Center - Hines
City
Hines
State/Province
Illinois
ZIP/Postal Code
60141
Country
United States
Facility Name
Swedish-American Regional Cancer Center
City
Rockford
State/Province
Illinois
ZIP/Postal Code
61104-2315
Country
United States
Facility Name
Hematology Oncology Associates of the Quad Cities
City
Bettendorf
State/Province
Iowa
ZIP/Postal Code
52722
Country
United States
Facility Name
Genesis Regional Cancer Center at Genesis Medical Center
City
Davenport
State/Province
Iowa
ZIP/Postal Code
52803
Country
United States
Facility Name
Siouxland Hematology-Oncology Associates, LLP
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51101
Country
United States
Facility Name
Mercy Medical Center - Sioux City
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51104
Country
United States
Facility Name
St. Luke's Regional Medical Center
City
Sioux City
State/Province
Iowa
ZIP/Postal Code
51104
Country
United States
Facility Name
University of Mississippi Cancer Clinic
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
CCOP - Montana Cancer Consortium
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
Hematology-Oncology Centers of the Northern Rockies - Billings
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
Northern Rockies Radiation Oncology Center
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
St. Vincent Healthcare Cancer Care Services
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
Billings Clinic - Downtown
City
Billings
State/Province
Montana
ZIP/Postal Code
59107-7000
Country
United States
Facility Name
Bozeman Deaconess Cancer Center
City
Bozeman
State/Province
Montana
ZIP/Postal Code
59715
Country
United States
Facility Name
St. James Healthcare Cancer Care
City
Butte
State/Province
Montana
ZIP/Postal Code
59701
Country
United States
Facility Name
Big Sky Oncology
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405-5309
Country
United States
Facility Name
Great Falls Clinic - Main Facility
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405
Country
United States
Facility Name
Sletten Cancer Institute at Benefis Healthcare
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405
Country
United States
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405
Country
United States
Facility Name
St. Peter's Hospital
City
Helena
State/Province
Montana
ZIP/Postal Code
59601
Country
United States
Facility Name
Glacier Oncology, PLLC
City
Kalispell
State/Province
Montana
ZIP/Postal Code
59901
Country
United States
Facility Name
Kalispell Medical Oncology at KRMC
City
Kalispell
State/Province
Montana
ZIP/Postal Code
59901
Country
United States
Facility Name
Kalispell Regional Medical Center
City
Kalispell
State/Province
Montana
ZIP/Postal Code
59901
Country
United States
Facility Name
Community Medical Center
City
Missoula
State/Province
Montana
ZIP/Postal Code
59801
Country
United States
Facility Name
Guardian Oncology and Center for Wellness
City
Missoula
State/Province
Montana
ZIP/Postal Code
59804
Country
United States
Facility Name
Montana Cancer Specialists at Montana Cancer Center
City
Missoula
State/Province
Montana
ZIP/Postal Code
59807-7877
Country
United States
Facility Name
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
City
Missoula
State/Province
Montana
ZIP/Postal Code
59807
Country
United States
Facility Name
Good Samaritan Cancer Center at Good Samaritan Hospital
City
Kearney
State/Province
Nebraska
ZIP/Postal Code
68848-1990
Country
United States
Facility Name
Kinston Medical Specialists
City
Kinston
State/Province
North Carolina
ZIP/Postal Code
28501
Country
United States
Facility Name
Summa Center for Cancer Care at Akron City Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44309-2090
Country
United States
Facility Name
Barberton Citizens Hospital
City
Barberton
State/Province
Ohio
ZIP/Postal Code
44203
Country
United States
Facility Name
Cancer Care Center, Incorporated
City
Salem
State/Province
Ohio
ZIP/Postal Code
44460
Country
United States
Facility Name
Cancer Treatment Center
City
Wooster
State/Province
Ohio
ZIP/Postal Code
44691
Country
United States
Facility Name
McLeod Regional Medical Center
City
Florence
State/Province
South Carolina
ZIP/Postal Code
29501
Country
United States
Facility Name
CCOP - Greenville
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
Medical City Dallas Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
Welch Cancer Center at Sheridan Memorial Hospital
City
Sheridan
State/Province
Wyoming
ZIP/Postal Code
82801
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16258090
Citation
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.
Results Reference
result
Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website

Learn more about this trial

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

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