Official Title: “A Randomised Phase II Feasibility Study of Docetaxel (Taxotere®) Plus Prednisolone vs. Docetaxel (Taxotere®) Plus Prednisolone Plus Zoledronic Acid (Zometa®) vs. Docetaxel (Taxotere®) Plus Prednisolone Plus Strontium-89 vs. Docetaxel (Taxotere®) Plus Prednisolone Plus Zoledronic Acid (Zometa®) Plus Strontium-89 in Hormone Refractory Prostate Cancer Metastatic to Bone.”

RATIONALE: Drugs used in chemotherapy, such as docetaxel and prednisolone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Zoledronic acid may help relieve some of the symptoms caused by bone metastases.

Radioactive substances, such as strontium chloride Sr 89, may help relieve bone pain caused by prostate cancer. Giving docetaxel together with prednisolone with or without zoledronic acid and/or strontium chloride Sr 89 may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying the side effects and how well giving docetaxel together with prednisolone works with or without zoledronic acid and/or strontium chloride Sr 89 in treating patients with prostate cancer metastatic to bone that has not responded to hormone therapy.

Study Type: Interventional

Study Design: Treatment, Randomized

Study Primary Completion Date: December 2008

OBJECTIVES:

Primary - To assess the toxicity and tolerability of docetaxel with zoledronic acid. - To assess the toxicity and tolerability of docetaxel with strontium chloride Sr 89. - To assess the toxicity and tolerability of docetaxel with zoledronic acid and strontium chloride Sr 89.

Secondary - Compare health economic endpoints between the treatment groups. - Compare changes in bone mineral density between the treatment groups. - Compare the biological profiling for prognostic and predictive indicators between the treatment groups.

Tertiary - Compare median time to disease progression between the treatment groups. - Compare pain progression-free survival (PFS) between the treatment groups. - Compare PSA PFS between the treatment groups. - Compare pain response between the treatment groups. - Compare overall survival between the treatment groups. - Compare quality of life between the treatment groups.

OUTLINE: This is a multicenter study. Patients are stratified according to treatment center and ECOG performance status (0 vs 1 vs 2). Patients are randomized to 1 of 4 treatment arms. - Arm I: Patients receive docetaxel IV on day 1 and oral prednisolone once daily. - Arm II: Patients receive docetaxel and prednisolone as in arm I and zoledronic acid IV over 15 minutes on day 1. - Arm III: Patients receive docetaxel and prednisolone as in arm I and a single dose of strontium chloride Sr 89 IV on day 7 of course 2. - Arm IV: Patients receive docetaxel and prednisolone as in arm I, zoledronic acid as in arm II, and strontium chloride Sr 89 as in arm III.

Treatment with docetaxel, prednisolone, and zoledronic acid repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Strontium chloride Sr 89 is given as a one time single dose.

Quality of life is assessed using the Euroqual (EQ-5D) and FACT-P at baseline and every 3 months during follow up.

After completion of study, patients are followed every 3 months.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

Intervention(s) in this Clinical Trial

• Drug: docetaxel
• Drug: prednisolone
• Drug: strontium chloride Sr 89
• Drug: zoledronic acid
• Procedure: quality-of-life assessment

Primary Measures

• Safety
  • Safety Issue?: Yes
• Toxicity and tolerability of docetaxel and zoledronic acid
  • Safety Issue?: Yes
• Toxicity and tolerability of docetaxel and strontium chloride Sr 89
  • Safety Issue?: Yes
• Toxicity and tolerability of docetaxel, zoledronic acid, and strontium chloride Sr 89
  • Safety Issue?: Yes

Secondary Measures

• Health Care economic analysis
  • Safety Issue?: No
• Changes in bone mineral density
  • Safety Issue?: No
• Median time to disease progression
  • Safety Issue?: No
• Pain progression-free survival (PFS)
  • Safety Issue?: No
• PSA PFS
  • Safety Issue?: No
• Pain response
  • Safety Issue?: No
• Overall survival
  • Safety Issue?: No
• Quality of life
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:
• Histologically or cytologically proven prostate adenocarcinoma
• Multiple sclerotic bone metastases with PSA ≥ 100 ng/mL without histological confirmation
• Radiological evidence of bone metastasis
• Prior hormonal therapy for prostate cancer including ≥ 1 of the following:
• Bilateral orchidectomy
• Medical castration by luteinizing hormone-releasing hormone (LHRH) agonist therapy
• If receiving LHRH agonist therapy alone, this therapy should be continued
• Documented disease progression, defined by one of the following:
• Progressive disease after discontinuing hormone therapy
• Elevated and rising PSA, defined as 2 consecutive increases in PSA documented over a previous reference value
• PSA > 5ng/mL
• Progression of any unidimensionally or bidimensionally measurable malignant lesion
• At least 1 new lesion identified on bone scan
• No known brain or leptomeningeal metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• Hemoglobin ≥ 10g/dL
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 1.5 times ULN (unless related to hepatic metastatic disease, where patients may be entered after discussion with one of the clinical advisors)
• Serum bilirubin ≤ 1.5 times ULN
• Physically fit enough to receive trial treatment
• No malignant disease within the past 5 years, other than adequately treated basal cell carcinoma
• No symptomatic peripheral neuropathy ≥ grade 2 (NCI CTC)
• No known hypersensitivity to bisphosphonates
• No condition, in the opinion of the investigator, that may interfere with the safety of the patient or evaluation of the study objectives

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior flutamide, nilutamide, or cyproterone acetate with evidence of disease progression since cessation
• At least 6 weeks since prior bicalutamide with evidence of disease progression since cessation
• At least 4 weeks since prior estramustine and any adverse events must have resolved
• At least 2 months since prior treatment with a bisphosphonate for any reason
• No treatment with any other investigational compound within the past 30 days
• No prior cytotoxic chemotherapy for hormone refractory prostate cancer (HRPC), other than estramustine monotherapy
• No prior radionuclide therapy for HRPC
• No prior radiotherapy to more than 25% of the bone marrow or whole pelvic irradiation
• No concurrent enrollment in any other investigational clinical trial

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University Hospital Birmingham

Overall Clinical Trial Officials and Contacts

Nicholas D. James, MD Study Chair University Hospital Birmingham  

Information obtained from ClinicalTrials.gov on August 08, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00554918

Study ID Number: CDR0000574585

ClinicalTrials.gov Identifier: NCT00554918

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database