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About
This phase I trial is studying the side effects and best dose of erlotinib when given together with gemcitabine and radiation therapy in treating patients with locally advanced unresectable pancreatic cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining erlotinib with gemcitabine may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells.
Full description
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of erlotinib given concurrently with gemcitabine and radiotherapy in patients with locally advanced unresectable pancreatic cancer.
SECONDARY OBJECTIVES:
I. Determine the toxicity of this regimen in these patients. II. Determine, preliminarily, the antitumor efficacy of this regimen, in terms of response rate, in these patients.
III. Determine the time to tumor progression and overall survival of patients treated with this regimen.
OUTLINE: This is a non-randomized, open-label, dose-escalation study of erlotinib.
Chemoradiotherapy: Patients undergo radiotherapy 5 days a week for 5.5 weeks. Beginning on day 1 and continuing concurrently with radiotherapy, patients receive gemcitabine IV over 30 minutes twice weekly and oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients receive treatment at that dose.
Patients are radiologically restaged 3-4 weeks after completion of radiotherapy. Patients with stable or responsive disease proceed to maintenance therapy. Patients whose imaging studies suggest a potential for curative resection are referred for a surgical evaluation before initiating maintenance therapy.
Maintenance therapy: Beginning 4-7 weeks after the completion of chemoradiotherapy, patients receive maintenance chemotherapy comprising gemcitabine IV over 30 minutes on days 1 and 8 and oral erlotinib once daily. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 19-28 patients will be accrued for this study.
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Inclusion and exclusion criteria
Inclusion Criteria:
Histologically or cytologically confirmed adenocarcinoma of the pancreas
Locally advanced, unresectable disease, defined by all of the following:
Locally recurrent disease after prior curative surgery allowed provided the following are true:
No islet cell pancreatic cancer or lymphoma or sarcoma of the pancreas
Measurable or evaluable disease
No known brain metastases
Performance status - ECOG 0-2
More than 12 weeks
WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ 1.5 mg/dL
AST and ALT ≤ 2.5 times upper limit of normal
Creatinine ≤ 2.0 mg/dL
Creatinine clearance ≥ 60 mL/min
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No abnormalities of the cornea based on history (e.g., dry eye syndrome or Sjögren's syndrome)
No congenital abnormality (e.g., Fuch's dystrophy)
No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
No abnormal corneal sensitivity test (Schirmer test or similar tear production test)
No Crohn's disease or inflammatory bowel disease that would preclude undergoing external beam radiotherapy
Able to tolerate oral medication
No requirement for IV alimentation
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No ongoing or active infection
No other concurrent uncontrolled illness
No psychiatric illness or social situation that would preclude study compliance
See Disease Characteristics
No prior gemcitabine
See Disease Characteristics
See Disease Characteristics
No prior epidermal growth factor receptor-targeting therapy
No prior therapy for pancreatic cancer (except surgery)
No concurrent commercial or other investigational agents or therapies intended to treat the malignancy
No concurrent combination antiretroviral therapy for HIV-positive patients
Primary purpose
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28 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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