Cetuximab/FOLFIRI With or Without Oxaliplatin and FOLFOXIRI With or Without Bevacizumab in Neoadjuvant Treatment of Non-resectable Colorectal Liver Metastases

NCT01802645 | Unknown Phase 2 DMC

• 2 other identifiers: TUD-CELIM2-0502011-003288-31
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 15

Brief Summary

The aim of this study is to investigate the following schedules for efficacy with regard to response rate in neoadjuvant treatment of patients with non-resectable liver metastases:

• Cetuximab/FOLFOXIRI and cetuximab/FOLFIRI in patients with ras wild type tumours and
• Bevacizumab/FOLFOXIRI and FOLFOXIRI in patients with ras mutant tumours.

Conditions

Colorectal Cancer

Keywords

neoadjuvant; cetuximab; irinotecan; bevacizumab; oxaliplatin; 5-FU; Resection; colorectal liver metastases; liver resection; Chemotherapy; k-ras; non-resectable

Outcome Measures

Primary Outcomes (1)

• Response rate

  Rate of patients with partial or complete response according to modified RECIST criteria.

  up to 1 year after randomization

Secondary Outcomes (1)

• Rate of resected patients without early relaps

  6 months after resection

Other Outcomes (8)

• R0 resection rate

  up to 1 year after randomization

• Resection rate

  up to 1 year after randomization

• Progression free survival

  up to 3 years after randomization

Study Arms (4)

Cetuximab/FOLFIRI

ACTIVE COMPARATOR

Cetuximab 250 mg/m² (1 h) weekly Irinotecan 180 mg/m² (1 h)\*, d-l Folinic acid 400 mg/m² (2 h), 5-FU 400 mg/m² (Bolus), 5-FU 2400 mg/m² (46 h) every 2 weeks \*reduced in UGT1A1 7/7 patients

Drug: Cetuximab; Drug: Irinotecan; Drug: 5-FU; Drug: Folinic Acid

Cetuximab/FOLFOXIRI

EXPERIMENTAL

Cetuximab 250 mg/m² (1 h) weekly Irinotecan 125 mg/m² (1 h),\* Oxaliplatin 85 mg/m² (2 h), d-l Folinic acid 400 mg/m² (2 h), 5-FU 3200 mg/m² (46 h) every 2 weeks \*reduced in UGT1A1 7/7 patients

Drug: Cetuximab; Drug: Irinotecan; Drug: Oxaliplatin; Drug: 5-FU; Drug: Folinic Acid

FOLFOXIRI

ACTIVE COMPARATOR

Irinotecan 165 mg/m² (1 h)\*, Oxaliplatin 85 mg/m² (2 h), d-l Folinic acid 400 mg/m² (2 h), 5-FU 3200 mg/m² (46 h) every 2 weeks \*reduced in UGT1A1 7/7 patients

Drug: Irinotecan; Drug: Oxaliplatin; Drug: 5-FU; Drug: Folinic Acid

Bevacizumab/FOLFOXIRI

EXPERIMENTAL

Bevacizumab 5 mg/kg (30-90 min i.v.), Irinotecan 165 mg/m² (1 h),\* Oxaliplatin 85 mg/m² (2 h), d-l Folinic acid 400 mg/m² (2 h), 5-FU 3200 mg/m² (46 h) every 2 weeks \*reduced in UGT1A1 7/7 patients

Drug: Bevacizumab; Drug: Irinotecan; Drug: Oxaliplatin; Drug: 5-FU; Drug: Folinic Acid

Interventions

Cetuximab DRUG

Also known as: Erbitux

Cetuximab/FOLFIRI; Cetuximab/FOLFOXIRI

Bevacizumab DRUG

Also known as: Avastin

Bevacizumab/FOLFOXIRI

Irinotecan DRUG

Also known as: Campto

Bevacizumab/FOLFOXIRI; Cetuximab/FOLFIRI; Cetuximab/FOLFOXIRI; FOLFOXIRI

Oxaliplatin DRUG

Also known as: Eloxatin

Bevacizumab/FOLFOXIRI; Cetuximab/FOLFOXIRI; FOLFOXIRI

5-FU DRUG

Also known as: 5-Fluorouracil

Bevacizumab/FOLFOXIRI; Cetuximab/FOLFIRI; Cetuximab/FOLFOXIRI; FOLFOXIRI

Folinic Acid DRUG

Also known as: Leukovorin

Bevacizumab/FOLFOXIRI; Cetuximab/FOLFIRI; Cetuximab/FOLFOXIRI; FOLFOXIRI

Eligibility Criteria

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

You may not qualify if:

• Any evidence of extrahepatic metastases, distant lymph node metastases and primary tumour recurrence
• (deleted)
• Prior systemic anti-tumour therapy with anti- EGFR-, anti-angiogenetic drugs or with chemotherapy (except adjuvant chemotherapy with an interval of ≥ 6 months or in combination with radiation as radio sensitizer)
• Radiotherapy or major abdominal or thoracic surgery (excluding diagnostic interventions or venous port implantation) ≤ 4 weeks before study entry
• Renal insufficiency with serum creatinine ≥ 1.5 x UNL. If serum creatinine is between 1.0 and 1.5 x UNL, the creatinine clearance according to the Cockroft-Gault formula should be ≥ 60 ml/min
• Hypertension with an arterial blood pressure \> 150/90 mmHg
• Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction within the last 12 months, significant arrhythmias)
• Known proteinuria \> 1 g/day (to be tested if proteinuria more than 1+ in the urinary dipstick analysis)
• Peripheral neuropathy \> CTC grade I
• Concurrent systemic immune therapy, chemotherapy, hormone therapy, or patients receiving immune suppressive treatment (i.e. for transplantation, severe rheumatologic disease)
• Participation in clinical trials with investigational agents within 30 days before start of the treatment in study
• Active treatment of
• peptic ulcers or bleeding erosive esophagitis / gastritis within 3 months before study
• pulmonary embolism, severe or unstable angina pectoris or myocardial infarction, stroke or transient ischemic attack within 12 months before study
• deep vein thrombosis within 4 weeks before study

Sponsors & Collaborators

• Technische Universität Dresden: lead

Study Sites (15)

Universitätsklinikum der RWTH Aachen

Aachen, 52074, Germany

Location

Charité Campus Virchow

Berlin, 13353, Germany

Location

Überörtliche Gemeinschaftspraxis Hämatologie/ Onkologie

Bocholt, 46397, Germany

Location

Klinikum Coburg GmbH

Coburg, 96450, Germany

Location

Onkologie Dülmen GbR

Coesfeld, 48653, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Klinikum der Johann Wolfgang Goethe Universität Frankfurt am Main

Frankfurt am Main, 60590, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Klinikum Landshut gGmbH

Landshut, 84034, Germany

Location

University hospital Leipzig

Leipzig, 04103, Germany

Location

Johannes-Gutenberg-Universität

Mainz, 55131, Germany

Location

Klinikum Oldenburg GmbH

Oldenburg, 26133, Germany

Location

Rems-Murr-Klinikum Winnenden

Winnenden, 71364, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Bevacizumab; Irinotecan; Oxaliplatin; Fluorouracil; Leucovorin

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; Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; 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

Study Officials

• Gunnar Folprecht, PD Dr.

  University hospital "Carl Gustav Carus" Dresden

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 11, 2013
• First Posted: March 1, 2013
• Study Start: March 1, 2013
• Primary Completion: September 1, 2019
• Study Completion: December 1, 2020
• Last Updated: September 11, 2019

Record last verified: 2019-09

Locations

DE (15)