A Trial of Chemo & Radiation Therapy for Pancreatic Cancer

Study Overview
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Brief Summary
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This is an open-label, non-randomized, combination study of cetuximab, gemcitabine, 5-FU, and external beam radiotherapy in patients with locally advanced, non-metastatic pancreatic cancer.

Detailed Description
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During cycle I (chemoradiation), gemcitabine (200 mg/m2) and cetuximab 400mg/m2 initial dose followed by 250mg/m2 IV weekly will be given with continuous infusion 5-FU (200 mg/m2/day) delivered 5 of every 7 days and concurrent external beam radiation therapy. Cetuximab, gemcitabine and 5-FU will begin on the first week of external beam radiotherapy and will continue throughout the course of external beam radiation therapy, and will be discontinued following the conclusion of external beam radiation therapy. All patients will have a central venous access device placed to facilitate chemotherapy administration. During cycles 2 through 5 (chemotherapy), gemcitabine will be administered at a dose of 1000 mg/m2 over 30 minutes followed by cetuximab at a dose of 250mg/m2 over 30 minutes weekly for 3 weeks followed by one-week rest for four cycles.

Official Title
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A Phase II Trial of Cetuximab, Gemcitabine, 5-Fluorouracil and Radiation Therapy in Locally Advanced Non-metastatic Pancreatic Adenocarcinoma

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Gemcitabine/Fluorouracil with External Beam Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological confirmation of pancreatic adenocarcinoma is required. Only patients with unresectable, non-metastatic tumors are eligible. Documentation of disease extent by endoscopic ultrasound and either laparotomy or laparoscopy must be performed within 42 days of registration. All patients will also be assessed by chest x-ray and abdominal-pelvic CT scan. Confirmation of palliative surgical bypass at the time of laparotomy or whether a biliary stent was placed will be requested. Disease must be locoregional and not amenable to surgery based on one or more of the following criteria: size of pancreatic tumor > 5 cm. lymph nodes (bulky, > 2 cm, but within a radiation port) vascular involvement or impingement of major vessels (superior mesenteric artery, superior mesenteric vein, portal vein, hepatic artery). invasion into the adjacent structures. Patients with either measurable or evaluable disease are eligible. Patients with evidence of peritoneal seeding by malignancy are not eligible for the study. Patients with other evidence of metastatic disease are not eligible. Patients with concurrent malignancy of any site, except limited basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, are ineligible. Patients with any other malignancy within 5 years of study entry, except curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, are ineligible. Patients may not have had prior therapy for carcinoma of the pancreas, nor prior abdominal radiation therapy. Age > 18 years. CTC performance status < 2. No myocardial infarction in the past six months. No major surgery in the past two weeks. No uncontrolled serious medical or psychiatric illness. Required Initial Laboratory Data: Total bilirubin < 2.0 mg/dl AST < 3x upper limits of normal. Serum creatinine < 2.0 mg/dl WBC > 3,000/mm3 (ANC>1500/mm3) Platelets > 100,000 mm3 CA 19-9 Required Diagnostic procedures: Chest X-ray Abdominal pelvic CT scan EUS Staging laparoscopy or staging laparotomy Exclusion Criteria: Enrollment in this trial will be limited to patients for whom protocol therapy is safe and appropriate. Physicians should consider the risks and benefits of therapy together with all relevant medical and other considerations in deciding whether this protocol is appropriate for a particular patient. Specific considerations include: Psychiatric illness which would prevent the patient from giving informed consent. Serious medical illness such as uncontrolled infection, severe cardiovascular disease including recent (< 6 months) myocardial infarction or uncontrolled congestive heart failure, or other serious illness which would limit anticipated survival to < 12 weeks. Protocol treatment would pose significant risk to an unborn child. Pregnant women should not be enrolled, and women of child-bearing age should be strongly encouraged to practice effective birth control during and for three months after the trial. Inability to swallow medication. Patients should have adequate, unassisted oral intake.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Gemcitabine/Fluorouracil with External Beam Radiation<br>This protocol will assess the antitumor activity of Gemcitabine/Fluorouracil with External Beam Radiation in patients with non-metastatic, locally advanced pancreatic carcinoma. | Drug: Gemcitabine/Fluorouracil with External Beam Radiation<br>* This protocol will assess the antitumor activity of gemcitabine (200 mg/m2 per week) and cetuximab (400mg/m2 loading dose followed by 250 mg/m2 weekly) when given with continuous infusion 5-FU (200 mg/m2/day/M-F) and daily concurrent external beam radiation therapy (50.4 Gy) in patients with non-metastatic, locally advanced pancreatic carcinoma.<br>* Other names: EGFR Expression; Cetuximab & Radiosensitization of Cetuximab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival of Patients With Locally Advanced Pancreatic Cancer Treated With Concurrent Gemcitabine, 5-FU, Cetuximab and External Beam Radiation Therapy. | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | 1-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker Response to Chemoradiation Therapy | 20% decrease in biomarker (CA19-9) from baseline | 1-year | 
| Resection Rate |  | 1-Year | 
| Overall Survival |  | Up to 2 years | 
| Toxicity Associated With This Regimen. |  | 1-Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, gemcitabine, 5-FU, cetuximab, radiation