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
- 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
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
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.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Survival rate as measured by Kaplan Meier method at 30 months
Theo Ruers, MD
Universitair Medisch Centrum St. Radboud - Nijmegen
United States: Federal Government