Docetaxel With or Without Imatinib Mesylate in Treating Patients With Androgen-Independent Prostate Cancer and Bone Metastases

Prostate Cancer Clinical Trial

Official title:

Randomized Double-Blind Phase II Trial of Docetaxel and Imatinib Versus Docetaxel and Placebo in Metastatic Androgen-Independent Prostate Cancer (AIPC) With Bone Metastases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00080678
• Other study ID #: CDR0000354505
• Secondary ID: MDA-ID-030008NOV
• Status: Completed
• Phase: Phase 2
• First received: April 7, 2004
• Last updated: October 10, 2012
• Start date: May 2003
• Est. completion date: March 2008

Study information

• Verified date: October 2012
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining docetaxel with imatinib mesylate may be effective treatment for androgen-independent prostate cancer and bone metastases.

PURPOSE: This randomized phase II trial is studying docetaxel and imatinib mesylate to see how well they work compared to docetaxel alone in treating patients with androgen-independent prostate cancer and bone metastases.

Description:

OBJECTIVES:

Primary

• Compare time to progression in patients with androgen-independent prostate cancer and bone metastases treated with docetaxel with vs without imatinib mesylate.

Secondary

• Compare the response rates in patients treated with these regimens.

• Compare the toxic effects of these regimens in these patients.

• Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to hemoglobin (< 11g/dL vs ≥ 11 g/dL), alkaline phosphatase (normal vs elevated), number of prior regimens (0 vs 1 or 2), and ECOG performance score (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive docetaxel IV on days 1, 8, 15, and 22 and oral imatinib mesylate once daily on days 1-43.

• Arm II: Patients receive docetaxel as in arm I and oral placebo once daily on days 1-43.

In both arms, courses repeat every 43 days in the absence of disease progression or unacceptable toxicity. Patients who progress on arm II may cross over to arm I.

PROJECTED ACCRUAL: A total of 152 patients (76 per treatment arm) will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: March 2008
• Est. primary completion date: August 2005
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of adenocarcinoma of the prostate

• Osseous metastases confirmed by radiography

• Lytic bone lesions considered for biopsy if there is clinical suspicion of histologic conversion to small cell carcinoma

• Failed prior hormonal therapy

• Progressive disease, as evidenced by one of the following:

• 2 consecutive rises in prostate-specific antigen (PSA) of at least 1 ng/mL over 4 weeks

• Increase of 25% of the product of bidimensional disease or 30% in maximum diameter

• Increase in number of osseous metastases by bone scan

• Worsening symptoms attributable to disease progression (e.g., worsening bony pain)

• PSA = 1 ng/mL

• Castrate serum testosterone = 50 ng/dL

• Concurrent luteinizing-hormone releasing-hormone analog required for medically castrated patients

• No small cell or sarcomatoid prostate cancers

• No uncontrolled CNS metastases

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• Eastern Cooperative Oncology Group (ECOG) 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute granulocyte count = 1,500/mm^3

• Platelet count = 100,000/mm^3

Hepatic

• Bilirubin = 1.5 mg/dL

• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) = 2 times upper limit of normal

• No chronic liver disease

Renal

• Creatinine clearance = 40 mL/min

Cardiovascular

• No New York Heart Association class III or IV congestive heart failure

• No unstable angina

• No myocardial infarction within the past 6 months

• No evidence of myocardial ischemia on electrocardiogram

• No uncontrolled severe hypertension

Pulmonary

• No oxygen-dependent lung disease

Other

• HIV negative

• No concurrent severe infection

• No contraindication to corticosteroids

• No uncontrolled diabetes mellitus

• No grade 2 or greater peripheral neuropathy

• No other malignancy within the past 2 years except nonmelanoma skin cancer

• No overt psychosis, mental disability, or incompetency that would preclude giving informed consent

• No history of noncompliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy

Chemotherapy

• No prior taxanes

• No more than 2 prior chemotherapy regimens

• At least 30 days since prior chemotherapy and recovered

• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics

• At least 4 weeks since prior flutamide or nilutamide*

• At least 6 weeks since prior bicalutamide* NOTE: *Unless there is evidence of interim disease progression

Radiotherapy

• At least 90 days since prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium and recovered

• At least 30 days since other prior radiotherapy and recovered

Surgery

• Fully recovered from prior surgery

Other

• No concurrent ketoconazole

• No concurrent warfarin

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Docetaxel

• Imatinib Mesylate

Locations

Country	Name	City	State
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

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)

Mathew P, Thall PF, Johnson MM, et al.: Preliminary results of a randomized placebo-controlled double-blind trial of weekly docetaxel combined with imatinib in men with metastatic androgen-independent prostate cancer (AIPC) and bone metastases (BM). [Abst

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression		Baseline to 3 years, or until disease progression	No
Secondary	Response rate		Up to 3 years	No
Secondary	Toxic effects		3 years	Yes