Imatinib Mesylate and Capecitabine in Treating Patients With Advanced Solid Tumors

Herbert Hurwitz

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: imatinib mesylate

Drug: capecitabine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00253565

CDR0000448905 (Other Identifier)

DUMC-3992-05-8R3

Pro00009521

NOVARTIS-DUMC-3992-05-8R3

ROCHE-DUMC-3992-05-8R3

Details and patient eligibility

About

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imatinib mesylate together with capecitabine may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate when given together with capecitabine in treating patients with advanced solid tumors.

Full description

OBJECTIVES:

Primary

Determine the maximum tolerated dose and recommended phase II dose of imatinib mesylate when administered with capecitabine in patients with advanced malignant solid tumors.

Secondary

Determine the non-dose-limiting toxic effects of this regimen in these patients.
Determine, preliminarily, the clinical activity of this regimen in these patients.
Determine the pharmacokinetics and pharmacogenetics of this regimen in these patients.
Determine, preliminarily, the effect of this regimen on wound angiogenesis in these patients.
Correlate pharmacokinetic parameters with clinical toxicity, clinical activity, or surrogate biomarker activity of this regimen in these patients.

OUTLINE: This is a dose escalation study of imatinib mesylate.

Patients receive oral capecitabine twice daily on days 1-14 and oral imatinib mesylate once or twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of patients receive escalating doses of imatinib mesylate until the maximum tolerated dose is determined.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed malignant solid tumors for which no standard effective therapy exists OR such therapy is refused
Previously treated brain metastases that are currently asymptomatic allowed

PATIENT CHARACTERISTICS:

Performance status

Karnofsky 70-100%

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count > 2,000/mm^3
Platelet count > 100,000 mm^3
Hemoglobin > 9.0 g/dL

Hepatic

Alkaline phosphatase < 2.5 times upper limit of normal (ULN)
SGOT and SGPT < 2.5 times ULN
Bilirubin < 1.5 times ULN

Renal

Creatinine clearance > 50 mL/min

Cardiovascular

No congestive heart failure
No symptomatic coronary artery disease
No uncontrolled cardiac arrhythmias
No myocardial infarction within the past 12 months
No other clinically significant cardiac disease

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
No prior unanticipated severe reaction to fluoropyrimidine therapy
No known sensitivity to fluorouracil

PRIOR CONCURRENT THERAPY:

Biologic therapy