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

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

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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Everolimus, Cetuximab, Irinotecan; Drug: Capecitabine, Oxaliplatine

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Department of Oncology, Aarhus Hospital
  • Odense, Denmark, 5000
    • Department of Oncology, Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent obtained prior to study entry?
2. Patient has histologically/cytologically proven, non-resectable or metastatic, adenocarcinoma of the pancreas?
3. Progressive disease during adjuvant chemotherapy (or within 6 month after) or progressive disease during or after first line chemotherapy?
4. Former treatment with chemotherapeutic agent containing gemcitabine?
5. Is the age of the patient ≥ 18 years?
6. Is the ECOG performance status 0-1?
7. Is the absolute neutrophil count (ANC) ≥ 1.5 x 109/l?
8. Is the platelet count ≥ 75 x 109/l?
9. Is the total bilirubin ≤1.5 x UNL (upper normal limit)?
10. Patient has normal liver function? (If liver metastases are present, there is no upper limit for ALAT/SPGT/alk phosph)?
11. Creatinine clearance ≥ 30 ml/min
12. Is the patient capable of following the treatment and the plan of evaluation?

Exclusion Criteria:

1. CTC Grade 3 hyperlipidaemia (>10.34 mmol/l) in spite of treatment
2. Active former or concurrent history of malignant neoplasm, in the last 2 years?
3. 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?
4. Pregnant or breast feeding patient (fertile patients must use contraceptives)?
5. 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)
6. Known hypersensitivity toward one or more of the parts in the treatment?

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Per Pfeiffer
• Collaborators: Odense University Hospital; Aarhus University Hospital
• Investigators: Principal Investigator: Per Pfeiffer, MD, Odense University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: January 4, 2010
• First Submitted That Met QC Criteria: January 4, 2010
• First Posted (Estimate): January 5, 2010

Study Record Updates

• Last Update Posted (Estimate): October 20, 2015
• Last Update Submitted That Met QC Criteria: October 18, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Capecitabine; Everolimus; Cetuximab; Irinotecan; Pancreas cancer; Oxaliplatin; Gemcitabine resistant pancreascancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Capecitabine; Oxaliplatin; Irinotecan; Everolimus; Cetuximab
• Other Study ID Numbers: ICE