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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00024167
First received: September 13, 2001
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: Docetaxel
Drug: Doxorubicin hydrochloride
Drug: Estramustine phosphate sodium
Drug: Ketoconazole
Drug: Prednisone
Drug: Vinblastine
Radiation: Strontium chloride Sr 89
Drug: Dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Randomized Phase III, Trial Comparing Consolidation Therapy With or Without Strontium-89 Following Induction Chemotherapy in Androgen-Independent Prostate Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Followed every 4 weeks until PSA progression then every 3 months ] [ Designated as safety issue: No ]

    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.



Enrollment: 265
Study Start Date: April 2002
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Doxorubicin hydrochloride
20 mg/m2 IV, day 1 on Weeks 1, 3, 5
Other Names:
  • Adramycin PFS
  • Adramycin RDF
  • Doxorubicin
Drug: Estramustine phosphate sodium
140 mg orally 3 x day, Days 1 through 7 on Weeks 2, 4, 6
Other Name: Estramustine
Drug: Ketoconazole
400 mg orally (po) 3 x day, Days 1 through 7
Other Name: Nizoral
Drug: Vinblastine
4 mg/m2 IVPB, Day 1 on Weeks 2, 4, 6
Other Name: Velban
Experimental: 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.
Drug: Docetaxel
75 mg/m2 intravenous piggyback (IVPB) over 1 hour, Day 1, every 3 weeks.
Other Name: Taxotere
Drug: Prednisone
5 mg orally 2 x daily, weeks 1-14
Drug: Dexamethasone
4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel.
Other Name: Decadron
Experimental: Consolidation arm I
Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy.
Drug: Doxorubicin hydrochloride
20 mg/m2 IV, day 1 on Weeks 1, 3, 5
Other Names:
  • Adramycin PFS
  • Adramycin RDF
  • Doxorubicin
Radiation: Strontium chloride Sr 89
One dose (4 mCi total dose) IV
Other Names:
  • strontium-89 chloride
  • Sr-89
  • strontium-89
  • Metastron
Experimental: Consolidation arm II
Doxorubicin as in Consolidation arm I.
Drug: Doxorubicin hydrochloride
20 mg/m2 IV, day 1 on Weeks 1, 3, 5
Other Names:
  • Adramycin PFS
  • Adramycin RDF
  • Doxorubicin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00024167

  Show 40 Study Locations
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Shi-Ming Tu, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00024167     History of Changes
Other Study ID Numbers: ID00-156, U10CA045809, P30CA016672, MDA-ID-00156, NCI-3410, CDR0000068897, NCI-2009-00009
Study First Received: September 13, 2001
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
adenocarcinoma of the prostate
stage IV prostate cancer
recurrent prostate cancer
Strontium-89
Induction Chemotherapy
Androgen-Independent Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Dexamethasone
Docetaxel
Doxorubicin
Estramustine
Ketoconazole
Liposomal doxorubicin
Prednisone
Vinblastine
14-alpha Demethylase Inhibitors
Alkylating Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antifungal Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014