Clinical trial NCT00080678: Docetaxel With or Without Imatinib Mesylate in Treating Patients With Androgen-Independent Prostate Cancer and Bone Metastases
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Cancer
Prostate Cancer
Keywords: adenocarcinoma of the prostate
recurrent prostate cancer
stage IV prostate cancer
bone metastases
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-08
Enrollment: 116
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Time to progression
timeFrame: Baseline to 3 years, or until disease progression
Secondary outcomes:
measure: Response rate
timeFrame: Up to 3 years
measure: Toxic effects
timeFrame: 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: M.D. Anderson Cancer Center at University of Texas
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Paul Mathew
role: STUDY_CHAIR
affiliation: M.D. Anderson Cancer Center
name: Christopher Logothetis, MD
role: STUDY_CHAIR
References:
citation: 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.