Chemotherapy and Bevacizumab With or Without Radiofrequency Ablation in Treating Unresectable Liver Metastases in Patients With Colorectal Cancer
- Conditions
- Colorectal CancerMetastatic Cancer
- Registration Number
- NCT00043004
- 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.
- Detailed Description
OBJECTIVES:
Primary
* Compare the 30-month overall survival rate of patients with unresectable liver metastases secondary to colorectal adenocarcinoma treated with chemotherapy and bevacizumab with or without radiofrequency interstitial ablation.
Secondary
* Compare overall survival of patients treated with these regimens.
* Compare quality of life of patients treated with these regimens.
* Determine the health economics associated with this study.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to treatment center, prior adjuvant chemotherapy for primary cancer (yes vs no), prior chemotherapy for liver metastases (yes vs no), and route of randomization (before surgery vs during surgery). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Within 4 weeks of randomization, patients undergo radiofrequency interstitial ablation (RFA) with or without additional resection of resectable lesions. Within 8 weeks after RFA, patients receive chemotherapy and bevacizumab.
* Arm II: Within 4 weeks of randomization, patients receive chemotherapy and bevacizumab.
In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.
Patients in both arms receive one of the following chemotherapy and bevacizumab regimens to be determined by participating center:
* Regimen A: Patients receive oxaliplatin IV over 2 hours on day 1 of weeks 1, 3, and 5 and leucovorin calcium IV over 2 hours followed by fluorouracil IV continuously over 24 hours on day 1 of weeks 1-6 and bevacizumab IV over 30-90 minutes on days 1 or 2, 15 or 16, and 29 or 30. Treatment repeats every 7 weeks for 4 courses.
* Regimen B: Patients receive oxaliplatin IV and leucovorin calcium IV over 2 hours on day 1 followed by fluorouracil IV continuously over 46 hours and bevacizumab IV over 30-90 minutes on day 1 or 3. Treatment repeats every 15 days for 12 courses.
* Regimen C: Patients receive oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours followed by fluorouracil IV continuously over 22 hours on days 1 and 2 and bevacizumab IV over 30-90 minutes on day 1 or 3. Treatment repeats every 15 days for 12 courses.
Quality of life is assessed at baseline, within 1 week after completion of RFA (arm I only), within 1 week before start of chemotherapy (arm I only), at weeks 6, 12, 18, and 24 during chemotherapy, every 3 months for 2 years after treatment, and then every 6 months thereafter.
After completion of study treatment, patients are followed every 3 months for 2½ years and then every 6 months thereafter.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: A total of 152 patients (71 per treatment arm) will be accrued for this study within 3 years.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 119
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Survival rate as measured by Kaplan Meier method at 30 months
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (43)
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
National Institute of Oncology
🇭🇺Budapest, Hungary
Churchill Hospital
🇬🇧Oxford, England, United Kingdom
Clatterbridge Centre for Oncology NHS Trust
🇬🇧Merseyside, England, United Kingdom
Cancer Research UK and University College London Cancer Trials Centre
🇬🇧London, England, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, England, United Kingdom
Royal South Hants Hospital
🇬🇧Southampton, England, United Kingdom
Glan Clywd District General Hospital
🇬🇧Rhyl, Denbighshire, Wales, United Kingdom
Velindre Cancer Center at Velindre Hospital
🇬🇧Cardiff, Wales, United Kingdom
Allgemeines Krankenhaus - Universitatskliniken
🇦🇹Vienna, Austria
Bristol Haematology and Oncology Centre
🇬🇧Bristol, England, United Kingdom
University College of London Hospitals
🇬🇧London, England, United Kingdom
Ziekenhuis Netwerk Antwerpen Middelheim
🇧🇪Antwerp, Belgium
Institut Jules Bordet
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Hopital Universitaire Hautepierre
🇫🇷Strasbourg, France
National Cancer Institute - Cairo
🇪🇬Cairo, Egypt
Azienda Ospedaliera S. Camillo-Forlanini
🇮🇹Rome, Italy
Jeroen Bosch Ziekenhuis
🇳🇱's-Hertogenbosch, Netherlands
Amphia Ziekenhuis - locatie Langendijk
🇳🇱Breda, Netherlands
Clinique Universitaire De Mont-Godinne
🇧🇪Mont-Godinne Yvoir, Belgium
Kliniken Essen - Mitte
🇩🇪Essen, Germany
Centre Hospitalier Regional et Universitaire d'Angers
🇫🇷Angers, France
Staedtische Kliniken Frankfurt am Main - Hoechst
🇩🇪Frankfurt, Germany
Centre Hospitalier Universitaire Ambroise Pare - Boulogne
🇫🇷Boulogne Billancourt, France
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
🇳🇱Amsterdam, Netherlands
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Maxima Medisch Centrum - Veldhoven
🇳🇱Veldhoven, Netherlands
Klinikum der Universitaet Regensburg
🇩🇪Regensburg, Germany
Klinikum der J.W. Goethe Universitaet
🇩🇪Frankfurt, Germany
Sahlgrenska University Hospital at Gothenburg University
🇸🇪Gothenburg (Goteborg), Sweden
Karolinska University Hospital - Huddinge
🇸🇪Stockholm, Sweden
Uppsala University Hospital
🇸🇪Uppsala, Sweden
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
🇬🇧Birmingham, England, United Kingdom
Atrium Medical Centre - Heerlen
🇳🇱Heerlen, Netherlands
Centre Alexis Vautrin
🇫🇷Vandoeuvre-les-Nancy, France
Medisch Centrum Leeuwarden - Zuid
🇳🇱Leeuwarden, Netherlands
Universitair Medisch Centrum St. Radboud - Nijmegen
🇳🇱Nijmegen, Netherlands
Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
🇩🇪Berlin, Germany
Universitair Ziekenhuis Gent
🇧🇪Ghent, Belgium
Leicester General Hospital
🇬🇧Leicester, England, United Kingdom
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands
Royal Liverpool University Hospital
🇬🇧Liverpool, England, United Kingdom