Docetaxel and Prednisolone 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

Prostate Cancer Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00554918
• Other study ID #: CRUK-TRAPEZE-2100
• Secondary ID: CDR0000574585EUD
• Status: Completed
• Phase: Phase 2
• First received: November 6, 2007
• Last updated: August 6, 2013
• Start date: February 2005
• Est. completion date: June 2013

Study information

• Verified date: April 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: June 2013
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bone Marrow Diseases
• Bone Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• docetaxel

• prednisolone

• zoledronic acid

Procedure:
• quality-of-life assessment

Radiation:
• strontium chloride Sr 89

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Ayr Hospital	Ayr	Scotland
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Gloucestershire Royal Hospital	Gloucester	England
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	Crosshouse Hospital	Kilmarnock	Scotland
United Kingdom	Mid Kent Oncology Centre at Maidstone Hospital	Maidstone	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Glan Clwyd Hospital	Rhyl, Denbighshire	Wales
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	Walsall Manor Hospital	Walsall	England
United Kingdom	Wishaw General Hospital	Wishaw	Scotland

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Birmingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety			Yes
Primary	Toxicity and tolerability of docetaxel and zoledronic acid			Yes
Primary	Toxicity and tolerability of docetaxel and strontium chloride Sr 89			Yes
Primary	Toxicity and tolerability of docetaxel, zoledronic acid, and strontium chloride Sr 89			Yes
Secondary	Health Care economic analysis			No
Secondary	Changes in bone mineral density			No
Secondary	Median time to disease progression			No
Secondary	Pain progression-free survival (PFS)			No
Secondary	PSA PFS			No
Secondary	Pain response			No
Secondary	Overall survival			No
Secondary	Quality of life			No

External Links

•   Clinical outcomes in patients with castrate-refractory prostate cancer (CRPC) metastatic to bone randomized in the factorial TRAPEZE trial to docetaxel (D) with strontium-89 (Sr89), zoledronic acid (ZA), neither, or both (ISRCTN 12808747).