Cetuximab in Neoadjuvant Treatment of Non-Resectable Colorectal Liver Metastases (CELIM)

NCT00153998 | Completed Phase 2

• 1 other identifier: CELIM
• Study Type: interventional
• Target: 135
• Locations: 2 countries
• Sites: 21

Brief Summary

General Objectives:

• To test the feasibility of neoadjuvant treatment with cetuximab/chemotherapy followed by liver resection
• To determine the optimal combination (cetuximab/FOLFOX versus cetuximab/FOLFIRI) for further trials in preoperative chemotherapy

Conditions

Colorectal Cancer; Liver Metastases

Keywords

Cetuximab; Oxaliplatin; Irinotecan; 5-FU; Chemotherapy; Resection; Liver resection; Neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Tumor response, defined as partial and complete response according to RECIST (Response Evaluation Criteria in Solid Tumors) - criteria in the intention-to-treat [ITT-] population

Secondary Outcomes (6)

• Rate of R0 liver resection (ITT- population)

• Progression free survival (ITT- population)

• Disease free survival after resection (ITT- population)

• Overall survival (ITT- population)

• Safety (all patients that received any study drug)

Study Arms (2)

1

ACTIVE COMPARATOR

Cetuximab and FOLFIRI

Drug: Cetuximab; Procedure: Liver resection; Drug: Cetuximab and FOLFIRI

2

ACTIVE COMPARATOR

Cetuximab and FOLFOX

Drug: Cetuximab; Procedure: Liver resection; Drug: Cetuximab and FOLFOX

Interventions

Cetuximab DRUG

1; 2

Liver resection PROCEDURE

1; 2

Cetuximab and FOLFIRI DRUG

Cetuximab 400 mg/m² (2.0 h i.v.) (first dose only), followed by: Cetuximab 250 mg/m² (1.0 h i.v.) weekly Irinotecan 180 mg/m² (2.0 h i.v.) all compounds day 1, repeated at day 15 Folinic acid (D,L) 400 mg/m² (2.0 h i.v.) 5-FU 400 mg/m² (bolus i.v.) 5-FU 2400 (-3000) mg/m² (46 h i.v.)

Also known as: Cetuximab(C225, Erbitux®, Merck KGaA), Irinotecan (irinotecan HCl, CPT-11 or Campto®, Aventis), 5-Fluorouracil (5-FU), Folinic acid (FA, i.e. Leucovorin®, Wyeth)

1

Cetuximab and FOLFOX DRUG

Cetuximab 400 mg/m² (2.0 h i.v.) (first dose only), followed by: Cetuximab 250 mg/m² (1.0 h i.v.) weekly Oxaliplatin 100 mg/m² (2.0 h i.v.) all compounds day 1, repeated at day 15 Folinic acid (D,L) 400 mg/m² (2.0 h i.v.) 5-FU 400 mg/m² (bolus i.v.) 5-FU 2400 (-3000) mg/m² (46 h i.v.)

Also known as: Cetuximab(C225, Erbitux®, Merck KGaA), Oxaliplatin (L-OHP, Eloxatin®, Sanofi-Synthelabo), 5-Fluorouracil (5-FU), Folinic acid (FA, i.e. Leucovorin®, Wyeth)

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with non-resectable, histologically confirmed, synchronous or metachronous colorectal liver metastases. Patients with non-resectable metastases are defined as; patients with five or more liver metastases; and/or patients with liver metastases that are technically non-resectable (local surgeon in cooperation with local radiologist will define non-resectability on the basis of remaining functional liver tissue, infiltration of all liver veins, infiltration of both liver arteries, both portal branches or both bile ducts).
• Patients with simultaneous liver metastases are eligible, if the primary tumor has been resected at least 1 month prior to chemotherapy.
• Karnofsky Performance Status ≥ 80
• Informed consent
• Adequate bone marrow function, liver and renal function (neutrophils \> 1.5 x 10\^9/l; thrombocytes \> 100 x 10\^9/l; hemoglobin \> 8.0 g/l; bilirubin ≤ 1.5 x upper limit of normal \[ULN\] and not increasing more than 25% within the last 4 weeks; ALAT and ASAT \< 5 x UNL; serum creatinine ≤ 1.5 x UNL)
• Age ≥ 18 years

You may not qualify if:

• Any evidence of extrahepatic metastases, lymph node metastases and primary tumor recurrence
• Prior chemotherapy (except adjuvant chemotherapy with an interval of ≥ 6 months)
• Previous exposure to EGFR (epidermal growth factor receptor)-targeting therapy
• Radiotherapy or major abdominal or thoracic surgery (excluding diagnostic biopsy or port implantation) ≤ 4 weeks before study entry
• Concurrent systemic immune therapy, chemotherapy, or hormone therapy
• Investigational agents or participation in clinical trials within 30 days before start of the treatment in study
• Clinically relevant coronary disease or myocardial infarction within 12 months before study entry
• Peripheral neuropathy \> CTC grade I
• Inflammatory bowel disease
• Previous malignancy (except colorectal cancer, history of basal cell carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment)
• History of severe psychiatric illness
• Drug or alcohol abuse
• Breast feeding or pregnant women, no effective contraception if risk of conception exists (male and female patients)

Sponsors & Collaborators

• Technische Universität Dresden: lead

Study Sites (21)

Medizinische Universitaet Wien, Universitaetsklinik für Chirurgie

Vienna, A-1090, Austria

Location

Kreiskrankenhaus Aschersleben

Aschersleben, 06449, Germany

Location

Charite-Campus Benjamin Franklin, Innere Medizin

Berlin, 12200, Germany

Location

Charite-Campus, Virchow-Klinikum, Innere Medizin

Berlin, 13353, Germany

Location

Allgemeines Krankenhaus Celle

Celle, 29223, Germany

Location

University Hospital "Carl Gustav Carus"

Dresden, 01307, Germany

Location

Florence-Nightingale-Krankenhaus

Düsseldorf, 40489, Germany

Location

Universitaet Erlangen-Nuernberg, Chirurgie

Erlangen, 91054, Germany

Location

Westdeutsches Tumorzentrum, Universitaetsklinikum Essen

Essen, 45112, Germany

Location

Johann Wolfgang Goethe Universitaet, Chirurgie

Frankfurt am Main, 60596, Germany

Location

Westpfalz-Klinikum GmbH Innere Medizin I

Kaiserslautern, 67653, Germany

Location

UKSH Campus Kiel, II. Medizinische Klinik

Kiel, 24116, Germany

Location

Staedtisches Klinikum Magdeburg-Olvenstedt

Magdeburg, 39130, Germany

Location

Universitaetsklinik Mannheim gGmbH, III. Medizinische Klinik

Mannheim, 68167, Germany

Location

Klinikum Grosshadern, III. Medizinische Klinik

München, 81377, Germany

Location

Klinikum Oldenburg GmbH

Oldenburg, 26133, Germany

Location

Klinikum Passau, II. Medizinische Klinik

Passau, 94032, Germany

Location

Klinikum der Hansestadt Stralsund GmbH, Medizinische Klinik

Stralsund, 18435, Germany

Location

Krankenhaus der Barmherzigen Brueder Trier, Chirurgie

Trier, 54292, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

Universitaetsklinikum Wuerzburg, Chirurgie

Würzburg, 97080, Germany

Location

Related Publications (2)

• Folprecht G, Gruenberger T, Bechstein W, Raab HR, Weitz J, Lordick F, Hartmann JT, Stoehlmacher-Williams J, Lang H, Trarbach T, Liersch T, Ockert D, Jaeger D, Steger U, Suedhoff T, Rentsch A, Kohne CH. Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study). Ann Oncol. 2014 May;25(5):1018-25. doi: 10.1093/annonc/mdu088. Epub 2014 Feb 27.

  PMID: 24585720 DERIVED

• Folprecht G, Gruenberger T, Bechstein WO, Raab HR, Lordick F, Hartmann JT, Lang H, Frilling A, Stoehlmacher J, Weitz J, Konopke R, Stroszczynski C, Liersch T, Ockert D, Herrmann T, Goekkurt E, Parisi F, Kohne CH. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010 Jan;11(1):38-47. doi: 10.1016/S1470-2045(09)70330-4. Epub 2009 Nov 26.

  PMID: 19942479 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Hepatectomy; Irinotecan; Fluorouracil; Leucovorin; Folfox protocol; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Digestive System Surgical Procedures; Surgical Procedures, Operative; Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Claus-Henning Köhne, Prof. Dr.

  Klinikum Oldenburg GmbH, Dr.-Eden-Str.10; 26133 Oldenburg

  PRINCIPAL INVESTIGATOR

• Gunnar Folprecht, Dr.

  University Hospital Dresden, Fetscherstr. 74, 01307 Dresden, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: November 1, 2004
• Primary Completion: March 1, 2008
• Last Updated: February 27, 2009

Record last verified: 2007-04

Locations

DE (20); AU (1)