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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00080678
First received: April 7, 2004
Last updated: October 10, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Metastatic Cancer
Prostate Cancer
Drug: Docetaxel
Drug: Imatinib Mesylate
Phase 2

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Time to progression [ Time Frame: Baseline to 3 years, or until disease progression ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Toxic effects [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 116
Study Start Date: May 2003
Study Completion Date: March 2008
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Docetaxel
Other Name: taxotere
Drug: Imatinib Mesylate
Other Names:
  • Imatinib
  • Gleevec
  • STI571
  • NSC-716051
Placebo Comparator: 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.
Drug: Docetaxel
Other Name: taxotere

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.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  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: NCT00080678

Locations
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Paul Mathew M.D. Anderson Cancer Center
Study Chair: Christopher Logothetis, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
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.

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00080678     History of Changes
Other Study ID Numbers: CDR0000354505, MDA-ID-030008, NOVARTIS-MDA-ID-030008, MSKCC-03132, DFCI-03187
Study First Received: April 7, 2004
Last Updated: October 10, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
adenocarcinoma of the prostate
recurrent prostate cancer
stage IV prostate cancer
bone metastases

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Prostatic Neoplasms
Bone Neoplasms
Bone Marrow Diseases
Neoplastic Processes
Pathologic Processes
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Androgens
Docetaxel
Imatinib
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014