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

NCT ID: NCT00080678

Last Updated: 2012-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-05-31
• Study Completion Date: 2008-03-31

Brief 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.

Detailed 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.

Conditions

Metastatic Cancer; Prostate Cancer

Keywords

adenocarcinoma of the prostate; recurrent prostate cancer; stage IV prostate cancer; bone metastases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Docetaxel + Imatinib Mesylate

Docetaxel 30 mg/m\^2 intravenous over 60 minutes on days 1, 8, 15, and 22 in 42-day cycles, with daily oral 600 mg imatinib mesylate.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Imatinib Mesylate

Intervention Type: DRUG

Docetaxel + Placebo

Docetaxel 30 mg/m\^2 intravenous (IV) over 60 minutes on days 1, 8, 15, and 22 in 42-day cycles, with daily oral placebo.

Group Type: PLACEBO_COMPARATOR

Docetaxel

Intervention Type: DRUG

Interventions

Docetaxel

Intervention Type: DRUG

Imatinib Mesylate

Intervention Type: DRUG

Other Intervention Names

taxotere; Imatinib; Gleevec; STI571; NSC-716051

Eligibility Criteria

Inclusion Criteria

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

• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Mathew

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Christopher Logothetis, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Countries

United States

References

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). [Abstract] J Clin Oncol 24 (Suppl 18): A-4562, 232s, 2006.

Reference Type: RESULT

Other Identifiers

MDA-ID-030008

Identifier Type: -

Identifier Source: secondary_id

NOVARTIS-MDA-ID-030008

Identifier Type: -

Identifier Source: secondary_id

MSKCC-03132

Identifier Type: -

Identifier Source: secondary_id

DFCI-03187

Identifier Type: -

Identifier Source: secondary_id

CDR0000354505

Identifier Type: -

Identifier Source: org_study_id