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

Pancreatic Cancer Clinical Trial

Official title:

Phase I/II Study of Gleevec (Imatinib Mesylate, Formerly Known as STI571) and Gemcitabine for Advanced Pancreas Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00281996
• Other study ID #: NU 02I8
• Secondary ID: NU-02I8NU-0948-0
• Status: Terminated
• Phase: Phase 1
• First received: January 24, 2006
• Last updated: August 24, 2011
• Start date: March 2005
• Est. completion date: October 2008

Study information

• Verified date: August 2011
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Gemcitabine
Administered intravenously over 30 minutes on days 1 and 8 of a 21-day cycle starting at a dose of 700 mg/m2 and increasing to 1000mg/m2 by cohorts
• Imatinib mesylate
Administered orally once daily with 8 ounces of water at a starting dose of 300 mg/day and increased to 600 mg/day according to cohort.

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine maximum tolerated dose according to toxicity		After 1 cycle of therapy (1 cycle = 21 days)	Yes
Primary	Clinical response rate		After every 2 cycles of study therapy (1 cycle = 21 days)	No
Primary	Overall survival at 6 months		After 6 months of study treatment	No