PhI Study of Erbitux & Gemcitabine w/Radiation Therapy for Locally Adv. Pancreas Ca

Study Overview
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Brief Summary
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RATIONALE: 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. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and help kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Cetuximab may also stop the growth of tumor cells by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Gemcitabine and cetuximab may make tumor cells more sensitive to radiation therapy. Giving gemcitabine together with cetuximab and radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of gemcitabine when given together with cetuximab and radiation therapy in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of gemcitabine hydrochloride when administered with cetuximab and radiotherapy in patients with unresectable locally advanced pancreatic or periampullary region cancer. Determine the toxicity of this regimen in these patients. OUTLINE: This is a dose-escalation study of gemcitabine hydrochloride. Patients receive cetuximab IV over 1-2 hours once weekly in weeks 1-7 and gemcitabine hydrochloride IV over 15-40 minutes once weekly in weeks 2-7. Patients also undergo radiotherapy 5 days a week in weeks 2-7. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride 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. After completion of study treatment, patients are followed for 30 days and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 12-30 patients will be accrued for this study.

Official Title
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A Phase I Study of Erbitux and Gemcitabine With Radiation Therapy for Locally Advanced Pancreas Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: gemcitabine hydrochloride
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the pancreas (head, body, or tail) or periampullary region, meeting both of the following criteria: Unresectable disease Locally advanced disease Measurable or evaluable disease by CT scan or MRI No evidence of metastatic disease outside of the planned irradiation field ECOG performance status 0-2 WBC ≥ 3,000/mm³ ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 8.5 g/dL AST and ALT ≤ 5 times upper limit of normal Bilirubin ≤ 2.0 mg/dL Creatinine ≤ 2.0 mg/dL No clinical indication of compromised function of nonirradiated kidney No secondary malignancies within the past 5 years except for resected nonmelanoma skin cancer or carcinoma in situ of the cervix Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Exclusion Criteria: No acute hepatitis No known HIV infection No other active or uncontrolled infection No significant history of uncontrolled cardiac disease, including any of the following: Hypertension Unstable angina Myocardial infarction within the past 6 months Congestive heart failure Cardiomyopathy with decreased ejection fraction No prior severe infusion reaction to a monoclonal antibody PRIOR CONCURRENT THERAPY: No prior radiotherapy to planned field of treatment No prior therapy that specifically and directly targets EGFR pathway At least 14 days since prior surgery or biopsy At least 28 days since prior bypass procedures More than 5 years since prior and no other concurrent chemotherapy No other concurrent investigational agent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic Intervention<br> | Biological: cetuximab<br>* 400mg/m2 initial dose week 1; followed by 250mg/m2/weekly starting week 2 with gemcitabine at fixed dose rate (10 mg/m2/min) + XRT. Cetuximab will start 1 week prior to all other treatment.<br>* Other names: Erbitux;Drug: gemcitabine hydrochloride<br>* Dose Level Gemcitabine dose Gemcitabine infusion -1 150mg/m2 15 Minutes 0 200mg/m2 20 minutes 300mg/m2 30 minutes 400mg/m2 40 minutes<br>* Other names: Gemzar;Radiation: radiation therapy<br>* 50.4 Gy, 28 fractions, 5.5 weeks (1.8 Gy/day). A cone down after 45 Gy will be performed to encompass gross disease with a margin of 1-1.5 cm. The prescription point will be designated at the intersection of the multiple beams. There are no planned interruptions > 3 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose |  | Weekly and 4 weeks after last dose of radiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity |  | Weekly and 4 weeks after last dose of radiation | 
| Toxicity |  | Weekly and 4 weeks after last dose of radiation | 
| Tumor response rate |  | 4 weeks after last dose of radiation and every 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III pancreatic cancer, adenocarcinoma of the pancreas, stage II pancreatic cancer, recurrent pancreatic cancer