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

This study has been completed.
Sponsor:
Information provided by:
Technische Universität Dresden
ClinicalTrials.gov Identifier:
NCT00153998
First received: September 8, 2005
Last updated: February 26, 2009
Last verified: April 2007
  Purpose

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

Condition Intervention Phase
Colorectal Cancer
Liver Metastases
Drug: Cetuximab
Procedure: Liver resection
Drug: Cetuximab and FOLFIRI
Drug: Cetuximab and FOLFOX
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open, Randomized, Multicenter, Randomized Phase II Trial Comparing the Combination of Cetuximab With Oxaliplatin/5-FU/FA Versus the Combination of Cetuximab With Irinotecan/5-FU/FA as Neoadjuvant Treatment in Patients With Non-Resectable Colorectal Liver Metastases

Resource links provided by NLM:


Further study details as provided by Technische Universität Dresden:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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)
  • Molecular predictive markers for response and toxicity

Enrollment: 135
Study Start Date: November 2004
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Cetuximab and FOLFIRI
Drug: Cetuximab Procedure: Liver resection Drug: Cetuximab and FOLFIRI

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.)

Other Names:
  • Cetuximab(C225, Erbitux®, Merck KGaA)
  • Irinotecan (irinotecan HCl, CPT-11 or Campto®, Aventis)
  • 5-Fluorouracil (5-FU)
  • Folinic acid (FA, i.e. Leucovorin®, Wyeth)
Active Comparator: 2
Cetuximab and FOLFOX
Drug: Cetuximab Procedure: Liver resection Drug: Cetuximab and FOLFOX

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.)

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

Detailed Description:

Patients with liver metastasis will be screened for this study. Eligible patients will complete the pretreatment evaluation including an abdominal CT scan that will be presented to the local surgeon and the radiologist for proving of resectability of hepatic lesions. Additionally, CT scans will be reviewed by three reference surgeons. In case of non-resectability, as defined above, CT- or ultrasound- guided biopsy of one of the liver metastases will be performed, unless biopsy material is available from prior biopsy of one of the liver metastases.

Instead of an ultrasound-guided biopsy, a CT-guided biopsy may be performed.

Formalin-fixed, paraffin embedded metastatic tissue will be sent to reference laboratory (Prof. Störkel, Wuppertal) for immunohistochemical analysis of EGFR- expression.

Additionally tissue will be stored in "RNA later" for gene expression analysis if agreed by the patient.

Additionally, the primary tumor will be collected and sent to the reference laboratory for analysis of EGFR- expression (if agreement of the patient exists).

Patients will be randomized to a combination of:

Cetuximab/FOLFIRI (irinotecan/5-FU/FA) or Cetuximab/FOLFOX6 (oxaliplatin/5-FU/FA)

All patients receive a four month treatment (eight cycles) of the allocated treatment.

Resection is planned after completion of neoadjuvant treatment and should be performed between 4 and 6 weeks after the last dose of chemotherapy. Probes of the resected material (in liquid nitrogen and paraffin embedded material will be collected).

If a resection is not possible after eight administrations of chemotherapy, chemotherapy will be continued until tumor progression (maximal duration of treatment 2 years) and the patient will be evaluated for a potential resection every two months.

After resection, postoperative treatment is planned for 3 months (6 cycles). Treatment start is planned between 4 and 8 weeks after the operation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00153998

Locations
Austria
Medizinische Universitaet Wien, Universitaetsklinik für Chirurgie
Wien, Austria, A-1090
Germany
Kreiskrankenhaus Aschersleben
Aschersleben, Germany, 06449
Charite-Campus Benjamin Franklin, Innere Medizin
Berlin, Germany, 12200
Charite-Campus, Virchow-Klinikum, Innere Medizin
Berlin, Germany, 13353
Allgemeines Krankenhaus Celle
Celle, Germany, 29223
University Hospital "Carl Gustav Carus"
Dresden, Germany, 01307
Florence-Nightingale-Krankenhaus
Duesseldorf, Germany, 40489
Universitaet Erlangen-Nuernberg, Chirurgie
Erlangen, Germany, 91054
Westdeutsches Tumorzentrum, Universitaetsklinikum Essen
Essen, Germany, 45112
Johann Wolfgang Goethe Universitaet, Chirurgie
Frankfurt Main, Germany, 60596
Westpfalz-Klinikum GmbH Innere Medizin I
Kaiserslautern, Germany, 67653
UKSH Campus Kiel, II. Medizinische Klinik
Kiel, Germany, 24116
Staedtisches Klinikum Magdeburg-Olvenstedt
Magdeburg, Germany, 39130
Universitaetsklinik Mannheim gGmbH, III. Medizinische Klinik
Mannheim, Germany, 68167
Klinikum Grosshadern, III. Medizinische Klinik
Muenchen, Germany, 81377
Klinikum Oldenburg GmbH
Oldenburg, Germany, 26133
Klinikum Passau, II. Medizinische Klinik
Passau, Germany, 94032
Klinikum der Hansestadt Stralsund GmbH, Medizinische Klinik
Stralsund, Germany, 18435
Krankenhaus der Barmherzigen Brueder Trier, Chirurgie
Trier, Germany, 54292
Universitaetsklinikum Tuebingen
Tuebingen, Germany, 72076
Universitaetsklinikum Wuerzburg, Chirurgie
Wuerzburg, Germany, 97080
Sponsors and Collaborators
Technische Universität Dresden
Investigators
Principal Investigator: 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
  More Information

No publications provided by Technische Universität Dresden

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Dr. Claus-Henning Köhne, now: Klinikum Oldenburg gGmbH
ClinicalTrials.gov Identifier: NCT00153998     History of Changes
Other Study ID Numbers: CELIM
Study First Received: September 8, 2005
Last Updated: February 26, 2009
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Technische Universität Dresden:
Cetuximab
Oxaliplatin
Irinotecan
5-FU
Chemotherapy
Resection
Liver resection
Neoadjuvant

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases
Fluorouracil
Oxaliplatin
Irinotecan
Cetuximab
Leucovorin
Folic Acid
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014