Chemotherapy and Bevacizumab With or Without Radiofrequency Ablation in Treating Unresectable Liver Metastases in Patients With Colorectal Cancer
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.
Drug: FOLFOX regimen
Drug: leucovorin calcium
Procedure: conventional surgery
Procedure: radiofrequency ablation
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||CLOCC Trial (Chemotherapy + Local Ablation Versus Chemotherapy) Randomized Phase II Study Of Local Treatment Of Liver Metastases By Radiofrequency Combined With Chemotherapy Versus Chemotherapy Alone In Patients With Unresectable Colorectal Liver Metastases|
- Survival rate as measured by Kaplan Meier method at 30 months [ Designated as safety issue: No ]
- Overall survival as measured by Logrank every 3 months for 30 months then every 6 months thereafter [ Designated as safety issue: No ]
- Progression-free survival as measured by Logrank every 3 months for 30 months then every 6 months thereafter [ Designated as safety issue: No ]
- Toxicity as measured by CTC version 2.0 every 3 months for 30 months then every 6 months thereafter [ Designated as safety issue: Yes ]
- 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 [ Designated as safety issue: No ]
- Response to treatment (arm II) as measured by RECIST criteria from start of treatment until disease progression [ Designated as safety issue: No ]
|Study Start Date:||May 2002|
|Primary Completion Date:||June 2007 (Final data collection date for primary outcome measure)|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00043004
Show 43 Study Locations
|Study Chair:||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|