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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00024167
• Other study ID #: ID00-156
• Secondary ID: U10CA045809P30CA
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2001
• Last updated: September 24, 2014
• Start date: April 2002

Study information

• Verified date: September 2014
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 265
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Docetaxel
75 mg/m2 intravenous piggyback (IVPB) over 1 hour, Day 1, every 3 weeks.
• Doxorubicin hydrochloride
20 mg/m2 IV, day 1 on Weeks 1, 3, 5
• Estramustine phosphate sodium
140 mg orally 3 x day, Days 1 through 7 on Weeks 2, 4, 6
• Ketoconazole
400 mg orally (po) 3 x day, Days 1 through 7
• Prednisone
5 mg orally 2 x daily, weeks 1-14
• Vinblastine
4 mg/m2 IVPB, Day 1 on Weeks 2, 4, 6

Radiation:
• Strontium chloride Sr 89
One dose (4 mCi total dose) IV

Drug:
• Dexamethasone
4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel.

Locations

Country	Name	City	State
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Barberton Citizens Hospital	Barberton	Ohio
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Billings Clinic - Downtown	Billings	Montana
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	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Northeast Georgia Medical Center	Gainesville	Georgia
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	CCOP - Greenville	Greenville	South Carolina
United States	St. Peter's Hospital	Helena	Montana
United States	Veterans Affairs Medical Center - Hines	Hines	Illinois
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
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	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	Cancer Care Center, Incorporated	Salem	Ohio
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Cancer Treatment Center	Wooster	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Duration of overall response measured from time measurement criteria met for complete response/partial response (CR/PR) (whichever is first recorded) until first date recurrent or progressive disease is objectively documented.; Duration of overall complete response measured from time measurement criteria first met for CR until first date that recurrent disease is objectively documented.	Followed every 4 weeks until PSA progression then every 3 months	No

External Links

•   University of Texas MD Anderson Cancer Center Website