Chemotherapy and Bevacizumab With or Without Radiofrequency Ablation in Treating Unresectable Liver Metastases in Patients With Colorectal Cancer

NCT00043004 | Terminated Phase 2

• 3 other identifiers: EORTC-40004ALM-CAO-EORTC-40004NCRI-EORTC-40004
• Study Type: interventional
• Target: 119
• Locations: 10 countries
• Sites: 43

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread by blocking blood flow. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiofrequency ablation uses high-frequency electric current to kill tumor cells. It is not yet known if chemotherapy is more effective with or without radiofrequency ablation in treating liver metastases. PURPOSE: This randomized phase II trial is studying combination chemotherapy, bevacizumab, and radiofrequency ablation to see how well they work compared to combination chemotherapy and bevacizumab alone in treating unresectable liver metastases in patients with colorectal cancer.

Conditions

Colorectal Cancer; Metastatic Cancer

Keywords

liver metastases; stage IV colon cancer; stage IV rectal cancer

Outcome Measures

Primary Outcomes (1)

• Survival rate as measured by Kaplan Meier method at 30 months

Secondary Outcomes (5)

• Overall survival as measured by Logrank every 3 months for 30 months then every 6 months thereafter

• Progression-free survival as measured by Logrank every 3 months for 30 months then every 6 months thereafter

• Toxicity as measured by CTC version 2.0 every 3 months for 30 months then every 6 months thereafter

• Quality of life as measured by Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 at baseline, weeks 6, 12, 18, and 24, every 3 months for years 1-2 after start of treatment, then every 6 months thereafter

• Response to treatment (arm II) as measured by RECIST criteria from start of treatment until disease progression

Interventions

bevacizumab BIOLOGICAL

FOLFOX regimen DRUG

fluorouracil DRUG

leucovorin calcium DRUG

oxaliplatin DRUG

conventional surgery PROCEDURE

radiofrequency ablation PROCEDURE

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Unresectable liver metastases secondary to colorectal adenocarcinoma, including: * Metastases that cannot be radically resected due to size, location, or number of deposits * Metastases invading right and left branches of hepatic artery or portal vein * Metastases extended to the 3 main hepatic veins * No detectable extra-hepatic disease * Fewer than 10 metastatic deposits on liver * Total metastatic involvement of liver no more than 50% * Adequate treatment of all metastatic lesions deemed possible either by radiofrequency interstitial ablation (RFA) alone or by a combination of resection of resectable lesions and RFA of the remaining unresectable lesions * Maximum diameter of 4 cm for lesions to be treated with RFA * No maximum diameter of lesions to be resected as long as negative resection margins are obtainable * If synchronous liver metastases, must have undergone prior resection of primary tumor PATIENT CHARACTERISTICS: Age * 18 to 80 Performance status * WHO 0-1 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count greater than 1,500/mm\^3 * Platelet count greater than 100,000/mm\^3 * No bleeding disorder or coagulopathy or need for full-dose anticoagulation Hepatic * Bilirubin less than 3 times upper limit of normal (ULN) * Alkaline phosphatase less than 3 times ULN Renal * Creatinine less than 2 times ULN * Protein \< 0.5 g/24 hr urine collection if proteinuria positive by dipstick Cardiovascular * No uncontrolled congestive heart failure * No uncontrolled angina pectoris * No uncontrolled hypertension * No uncontrolled arrhythmia * No myocardial infarction within the past 12 months * No cerebrovascular accident or transient ischemic attack within the past 6 months Other * Not pregnant or nursing * Fertile patients must use effective contraception * No greater than grade 1 peripheral neuropathy * No significant neurologic or psychiatric disorder * No active infection * No contraindication to the use of fluorouracil, leucovorin calcium, oxaliplatin, or bevacizumab * No other malignancy within the past 10 years except nonmelanoma skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy except for metastatic disease confined to the liver * Prior fluorouracil, leucovorin calcium, and oxaliplatin allowed if administered for at least 3 courses (2 weeks each) but no longer than 3 months with at least stabilization of disease achieved * Prior adjuvant chemotherapy for primary cancer allowed except for patients who received oxaliplatin and have been diagnosed with metastatic disease within 12 months after completion of adjuvant treatment Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * More than 28 days since major surgery or open biopsy past 28 days * More than 28 days since significant traumatic injury Other * No other concurrent investigational treatment * No other concurrent anticancer therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Arbeitsgruppe Lebermetastasen und Tumoren: collaborator
• Institute of Cancer Research, United Kingdom: collaborator

Study Sites (43)

Allgemeines Krankenhaus - Universitatskliniken

Vienna, A-1090, Austria

Location

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, 2020, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, B-2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, B-9000, Belgium

Location

Clinique Universitaire De Mont-Godinne

Mont-Godinne Yvoir, 5530, Belgium

Location

National Cancer Institute - Cairo

Cairo, Egypt

Location

Centre Hospitalier Regional et Universitaire d'Angers

Angers, 49033, France

Location

Centre Hospitalier Universitaire Ambroise Pare - Boulogne

Boulogne-Billancourt, F-92104, France

Location

Hopital Universitaire Hautepierre

Strasbourg, 67098, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch

Berlin, D-13122, Germany

Location

Kliniken Essen - Mitte

Essen, D-45136, Germany

Location

Klinikum der J.W. Goethe Universitaet

Frankfurt, D-60590, Germany

Location

Staedtische Kliniken Frankfurt am Main - Hoechst

Frankfurt, D-65929, Germany

Location

Klinikum der Universitaet Regensburg

Regensburg, D-93053, Germany

Location

National Institute of Oncology

Budapest, 1122, Hungary

Location

Azienda Ospedaliera S. Camillo-Forlanini

Rome, 00152, Italy

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5211 NL, Netherlands

Location

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, 1066 CX, Netherlands

Location

Amphia Ziekenhuis - locatie Langendijk

Breda, 4800 RL, Netherlands

Location

Medisch Spectrum Twente

Enschede, 7500 KA, Netherlands

Location

Atrium Medical Centre - Heerlen

Heerlen, 6401 CX, Netherlands

Location

Medisch Centrum Leeuwarden - Zuid

Leeuwarden, 8934 AD, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, 6202 AZ, Netherlands

Location

Universitair Medisch Centrum St. Radboud - Nijmegen

Nijmegen, NL-6500 HB, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Maxima Medisch Centrum - Veldhoven

Veldhoven, 5500 MB, Netherlands

Location

Sahlgrenska University Hospital at Gothenburg University

Gothenburg (Goteborg), S-413 45, Sweden

Location

Karolinska University Hospital - Huddinge

Stockholm, S - 141 86, Sweden

Location

Uppsala University Hospital

Uppsala, SE 75185, Sweden

Location

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

Birmingham, England, B15 2TH, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, England, BS2 8ED, United Kingdom

Location

Leicester General Hospital

Leicester, England, LE5 4PW, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, England, L69 3GA, United Kingdom

Location

Cancer Research UK and University College London Cancer Trials Centre

London, England, NW1 2ND, United Kingdom

Location

University College of London Hospitals

London, England, WIT 3AA, United Kingdom

Location

Manchester Royal Infirmary

Manchester, England, M13 9WL, United Kingdom

Location

Clatterbridge Centre for Oncology NHS Trust

Merseyside, England, CH63 4JY, United Kingdom

Location

Churchill Hospital

Oxford, England, OX3 7LJ, United Kingdom

Location

Royal South Hants Hospital

Southampton, England, SO14 0YG, United Kingdom

Location

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, CF14 2TL, United Kingdom

Location

Glan Clywd District General Hospital

Rhyl, Denbighshire, Wales, LL 18 5UJ, United Kingdom

Location

Related Publications (2)

• Ruers T, van Coevorden F, Pierie J, et al.: Radiofrequency ablation (RFA) combined with chemotherapy for unresectable colorectal liver metastases (CRC LM): interim results of a randomised phase II study of the EORTC-NCRI CCSG-ALM Intergroup 40004 (CLOCC). [Abstract] J Clin Oncol 26 (Suppl 15): A-9535, 2008.

  RESULT

• Ruers T, Punt C, Van Coevorden F, Pierie JPEN, Borel-Rinkes I, Ledermann JA, Poston G, Bechstein W, Lentz MA, Mauer M, Van Cutsem E, Lutz MP, Nordlinger B; EORTC Gastro-Intestinal Tract Cancer Group; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO) and the National Cancer Research Institute Colorectal Clinical Study Group (NCRI CCSG). Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol. 2012 Oct;23(10):2619-2626. doi: 10.1093/annonc/mds053. Epub 2012 Mar 19.

  PMID: 22431703 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Folfox protocol; Fluorouracil; Leucovorin; Oxaliplatin; Radiofrequency Ablation

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Theo Ruers, MD

  Universitair Medisch Centrum St. Radboud - Nijmegen

  STUDY CHAIR

• Wolf O. Bechstein, MD

  Arbeitsgruppe Lebermetastasen und Tumoren

  STUDY CHAIR

• Jonathan A. Ledermann, MD

  Cancer Research UK

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2002
• First Posted: January 27, 2003
• Study Start: May 1, 2002
• Primary Completion: June 1, 2007
• Last Updated: September 24, 2012

Record last verified: 2012-09

Locations

EG (1); HU (1); FR (4); IT (1); NL (10); SE (3); BE (5); GB (12); DE (5); AU (1)