A Clinical Study of UFT/Leucovorin, Radiotherapy With or Without Cetuximab Following Induction Gemcitabine Plus Capecitabine in Patients With Locally Advanced Pancreatic Cancer (PERU)

Study Overview
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Brief Summary
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The purpose is to assess the overall survival of patients receiving either UFT/LV + radiotherapy (RT) or UFT/LV + Cetuximab + RT after neo-adjuvant chemotherapy.

Detailed Description
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Locally advanced pancreatic cancer carries a poor prognosis with no survival advantage of CRT over chemotherapy alone. 4 Phase II- III studies patients without disease progression after 3 months of systemic chemotherapy and CRT had a longer survival than those continuing on chemotherapy. Therefore chemotherapy followed by CRT may be a better approach. Also the effect of blocking EGFR will be evaluated in locally advanced pancreatic cancer. Gemcitabine and capecitabine combination will be used as neo-adjuvant chemotherapy.

Official Title
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A Multicentre Randomised Phase II Clinical Study of UFT/Leucovorin, Radiotherapy With or Without Cetuximab Following Induction Gemcitabine Plus Capecitabine in Patients With Locally Advanced Pancreatic Cancer (PERU)

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Other: UFT, Leucovorin
* Other: UFT/ Leucovorin + Cetuximab + Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 Histological or cytological diagnosis of adeno- or undifferentiated non-small cell carcinoma of pancreas. Considered to be unresectable based on following: extensive peri-pancreatic lymph node involvement, encasement or occlusion of the SMV or SMV/portal vein confluence, direct involvement of SMA, coeliac axis, inferior vena cava or aorta. Performance status 0-2 No evidence of metastatic disease as determined by CT scan/ other investigations Adequate bone marrow function with platelets>100^9/l; WBC>3x10^9/l;neutrophils> 1.5x10^9/l Serum bilirubin ,1.5 x ULN and transaminases < 2.5 x ULN Calculated/measured GFR >50ml/min No concurrent uncontrolled medical condition No active malignant disease other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix over the last 10 years Life expectancy > 3months Adequate contraceptive precautions Informed written consent Exclusion Criteria: medical or psychiatric conditions that compromise the patient's ability to give informed consent Presence of met. disease Concurrent uncontrolled medical conditions Any previous chemo/RT or any investigational treatment for advanced pancreatic cancer. Adjuvant chemo + fluoropyrimidine or gemcitabine within 12months of trial entry Adjuvant RT with/without chemo for pancreatic cancer. Pregnancy/breast feeding Patients with known malabsorption syndromes ro a lack of physical treatment of the upper GI tract. Patients with a known hypersensitivity to 5-FU or with a DPD deficiency. Clinically significant CVD

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>UFT/LV + RT | Other: UFT, Leucovorin<br>* UFT 300mg/m2/day in 3 equal doses and Leucovorin 90mg/day in 3 divided doses per day given daily on the days of radiotherapy only (30 days in total)<br>|
| Active Comparator: Group 2<br>UFT/LV + RT + Cetuximab | Other: UFT/ Leucovorin + Cetuximab + Radiotherapy<br>* UFT 300mg/m2 + LV 90mg/day on days of RT only (30 days in total), Cetuximab 400mg/m2 week 1, thereafter 250mg/m2 weeks 2-6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One year overall survival, measured from the date of registration. |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | three years | 
| Characterise safety profile of UFT/leucovorin, radiotherapy with or without cetuximab following induction gemcitabine plus capecitabine in patients with locally advanced pancreatic cancer |  | three years | 
| Objective response rate |  | three years | 
| Pattern of failure |  | up to 3 years | 
| Quality of life |  | up to 3 years | 
| Evaluation of molecular and genetic predictors of response to anti-EGFR treatment |  | up to 3 years | 
| Evaluation of changes in diffusion weighted MRI parameters in pancreatic cancer patients before and after treatment. |  | up to 3 years | 
| Evaluation of the role of FDG-PET in predicting overall survival, progression free survival and objective response rate in locally advanced pancreatic cancer. |  | up to 3 years |