Imatinib Mesylate and Gemcitabine in Treating Patients With Locally Advanced, Metastatic, or Recurrent Pancreatic Cancer

Northwestern University

Status and phase

Terminated

Phase 1

Conditions

Pancreatic Cancer

Treatments

Drug: Gemcitabine

Drug: Imatinib mesylate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00281996

NU-02I8

NU 02I8

NU-0948-003

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. Drugs used in chemotherapy, such as gemcitabine, 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 gemcitabine may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving imatinib mesylate together with gemcitabine and to see how well they work in treating patients with locally advanced, metastatic, or recurrent pancreatic cancer.

Full description

OBJECTIVES:

Primary

Determine the maximum tolerated dose of imatinib mesylate and gemcitabine hydrochloride in patients with locally advanced, metastatic, or recurrent pancreatic cancer.
Determine the clinical response rate in patients treated with this regimen.
Determine the 6-month and overall survival of patients treated with this regimen.

Secondary

Determine the toxicity profile of this regimen in these patients.
Correlate response with expression of platelet-derived growth factor (PDGF) and PDGF receptor in tumor tissue from patients treated with this regimen.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Phase I: Patients receive oral imatinib mesylate once daily on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8*. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-5 patients receive escalating doses of imatinib mesylate and gemcitabine hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 5 or 3 of 5 patients experience dose-limiting toxicity.

NOTE: *The first cohort receives gemcitabine hydrochloride on days 1, 8, and 15

Phase II: Patients receive imatinib mesylate and gemcitabine hydrochloride at the MTD determined in phase I in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Enrollment

19 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed pancreatic cancer
- Locally advanced, metastatic, or recurrent disease
Measurable or evaluable disease by physical exam, plain radiographs, CT scan, or MRI
No brain metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy of 12 weeks or greater
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
No chronic liver disease (i.e., chronic active hepatitis or cirrhosis)
Creatinine ≤ 2.0 mg/dL
No chronic renal disease
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier-method contraception during and for ≥ 3 months after completion of study treatment
No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix
No uncontrolled diabetes
No active uncontrolled infection
No other severe and/or uncontrolled medical disease
HIV negative

PRIOR CONCURRENT THERAPY:

No prior therapy for metastatic disease
- Prior fluorouracil as a radiosensitizer for adjuvant therapy after surgery or for locally advanced disease is permitted if local disease has recurred or progressed ≥ 3 months after completion of therapy or disease is present outside the radiation field
At least 2 weeks since prior major surgery
No concurrent grapefruit or grapefruit juice