A Randomised Trial With Irinotecan, Cetuximab and Everolimus (ICE)Compared to Capecitabine and Oxaliplatin (CapOx) for Patients With Gemcitabin Resistant Pancreatic Cancer

Study Overview
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Brief Summary
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This is an open multicenter randomized phase I/II study. The main purpose with this study is to investigate dose and efficacy of a combination of Irinotecan, Cetuximab and Everolimus given biweekly to patients with local advanced or metastatic pancreatic cancer AFTER progression from 1. line treatment with Gemcitabine.

Official Title
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A Randomised Fase I/II Trial With Irinotecan, Cetuximab and Everolimus (ICE)Compared to Capecitabine and Oxaliplatin (CapOx) for Patients With Gemcitabin Resistant Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Everolimus, Cetuximab, Irinotecan
* Drug: Capecitabine, Oxaliplatine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained prior to study entry? Patient has histologically/cytologically proven, non-resectable or metastatic, adenocarcinoma of the pancreas? Progressive disease during adjuvant chemotherapy (or within 6 month after) or progressive disease during or after first line chemotherapy? Former treatment with chemotherapeutic agent containing gemcitabine? Is the age of the patient ≥ 18 years? Is the ECOG performance status 0-1? Is the absolute neutrophil count (ANC) ≥ 1.5 x 109/l? Is the platelet count ≥ 75 x 109/l? Is the total bilirubin ≤1.5 x UNL (upper normal limit)? Patient has normal liver function? (If liver metastases are present, there is no upper limit for ALAT/SPGT/alk phosph)? Creatinine clearance ≥ 30 ml/min Is the patient capable of following the treatment and the plan of evaluation? Exclusion Criteria: CTC Grade 3 hyperlipidaemia (>10.34 mmol/l) in spite of treatment Active former or concurrent history of malignant neoplasm, in the last 2 years? Any condition or therapy which, by the investigators opinion, will expose the patient to a risk or will affect the purpose of the clinical trial? Pregnant or breast feeding patient (fertile patients must use contraceptives)? Infections or other serious medical conditions, which can obstruct the patient's possibility of receiving the treatment? (for instance serious heart, metabolic or lung disease) Known hypersensitivity toward one or more of the parts in the treatment?

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase II: Arm A<br>Regime A-ICE On progression or unacceptable toxicity patients can cross-over from regime A to regime B | Drug: Everolimus, Cetuximab, Irinotecan<br>* Cetuximab 500 mg/m² iv biweekly Irinotecan 180 mg/m² iv biweekly Everolimus in daily MDT dosage<br>* Other names: RAD001;|
| Active Comparator: Arm B<br>Arm B: CapOx On progression or unacceptable toxicity patients can cross-over from regime B to regime A. | Drug: Capecitabine, Oxaliplatine<br>* Capecitabine 1250 mg/m² bid. Oxaliplatin 70 mg/m² biweekly<br>* Other names: Xeloda, Eloxatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Establish maximum tolerable (MTD) dose of ICE (Irinotecan, Cetuximab and Everolimus) |  | 4 months | 
| Phase I: Determine the maximum tolerated dose (MTD) of ICE in patients with gemcitabine resistant pancreatic cancer |  | 4 months | 
| Phase II: Progression-free survival as measured from inclusion to either documentation of disease progression or death |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival All events grade 1-5 according to NCI-CTCAE in fase I All Adverse events grade 1-5 according to NCI-CTCAEW in Fase II Correlation between effect of treatment and tumourmarkers Quality of life - EORTC QLQ Time to failure of Strategy |  | 22 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreas cancer, Everolimus, Irinotecan, Cetuximab, Capecitabine, Oxaliplatin, Gemcitabine resistant pancreascancer