A Phase 1 Study Investigating the Combination of RAD001, Cetuximab and Irinotecan as Second-line Therapy After FOLFOX (or XELOX) Plus Bevacizumab in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This study will assess the safety of RAD001 when given together with cetuximab and irinotecan

Official Title
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An Open-label, Multicenter Phase 1 Study Investigating the Combination of RAD001, Cetuximab and Irinotecan as Second-line Therapy After FOLFOX (or XELOX) Plus Bevacizumab (if Given as Part of Local Standard Practice) in Patient With Metastatic Colorectal Adenocarcinoma

Conditions
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Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors, Neoplasms, Colorectal

Intervention / Treatment
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* Drug: RAD001, Cetuximab, Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age ≥ 18 years old and ≤ 65 years old. Patients with metastatic CRC. Confirmation of CRC diagnosis by histological or cytological specimen from original resection of primary tumor. Patients who progressed despite prior therapy with FOLFOX (5FU and oxaliplatin) plus bevacizumab or XELOX (capecitabine and oxaliplatin) plus bevacizumab. Patients with at least one measurable lesion by RECIST as determined by Computer Tomography (CT) Scan, Magnetic Resonance Imaging (MRI) or physical examination. Patients with a WHO performance status of 0 or 1. Exclusion criteria: Patients with Gilbert's syndrome or any other syndrome associated with deficient glucoronidation of bilirubin. Patients who are homozygous for the UGT1A1*28 allele as determined by sequencing. Patients who have received previous irinotecan-based therapy. Prior treatment with an mTOR inhibitor. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1: RAD001 + cetuximab + irinotecan<br>RAD001 30mg weekly oral, 400mg/m2, loading i.v. (250mg/m2 for subsequent weekly dose i.v.), 350mg/m2 every 3 weeks i.v. | Drug: RAD001, Cetuximab, Irinotecan<br> <br> |
| Experimental: B1 dose: RAD001 + cetuximab + irinotecan<br>RAD001 30mg weekly oral, 400mg/m2 loading i.v (250mg/m2 for subsequent weekly dose i.v.), 250mg/m2 every 3 weeks i.v. | Drug: RAD001, Cetuximab, Irinotecan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities | each cycle was 21 days | at end of cycle 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of RAD001, Irinotecan and SN-38 |  |  | 
| Progressions Free Survival |  |  | 
| Overall Survival |  |  | 
| Objective Response Rate |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors, Neoplasms, Colorectal