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
18 Years
80 Years
Both
Colorectal Cancer, Metastatic Cancer
Trial Information
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
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Survival rate as measured by Kaplan Meier method at 30 months
Safety Issue:
No
Principal Investigator
Theo Ruers, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Universitair Medisch Centrum St. Radboud - Nijmegen
Authority:
United States: Federal Government
Study ID:
EORTC-40004
NCT ID:
NCT00043004
Start Date:
May 2002
Completion Date:
Related Keywords:
- Colorectal Cancer
- Metastatic Cancer
- liver metastases
- stage IV colon cancer
- stage IV rectal cancer
- Colorectal Neoplasms
- Neoplasm Metastasis
- Neoplasms
- Neoplasms, Second Primary
- Liver Neoplasms
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