Randomized Phase II Trial Evaluating the Feasibility and Tolerance of the Combination of FOLFOX With Cetuximab and the Combination of FOLFOX With Cetuximab and Bevacizumab as Perioperative Treatment in Patients With Resectable Liver Metastases From Colorectal Cancer
18 Years
80 Years
Both
Colorectal Cancer, Metastatic Cancer
Trial Information
Randomized Phase II Trial Evaluating the Feasibility and Tolerance of the Combination of FOLFOX With Cetuximab and the Combination of FOLFOX With Cetuximab and Bevacizumab as Perioperative Treatment in Patients With Resectable Liver Metastases From Colorectal Cancer
OBJECTIVES:
- Compare the safety and activity of neoadjuvant and adjuvant cetuximab, leucovorin
calcium, oxaliplatin, and fluorouracil with vs without bevacizumab in patients with
resectable liver metastases secondary to colorectal cancer.
OUTLINE: This is an open-label, randomized, multicenter study. Patient are stratified
according to participating center and planned liver resection (major [≥ 3 segments] vs minor
[< 3 segments]). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2
hours on day 1 and fluorouracil IV over 46 hours (FOLFOX) beginning on day 1. Patients
also receive cetuximab IV over 1-2 hours on days 1 and 8. Treatment repeats every 14
days for 6 courses in the absence of disease progression or unacceptable toxicity.
Between 3-5 weeks after completion of FOLFOX and cetuximab, patients undergo liver
resection. Beginning between 4-8 weeks after surgery, patients receive another 6 courses of
FOLFOX and cetuximab as in neoadjuvant therapy.
- Arm II: Patients receive FOLFOX and cetuximab as in arm I and bevacizumab IV over 30-90
minutes on day 1. Treatment repeats every 14 days for 6 courses* in the absence of
disease progression or unacceptable toxicity.
NOTE: *Patients do not receive bevacizumab during course 6
Between 3-5 weeks after completion of FOLFOX, cetuximab, and bevacizumab, patients undergo
liver resection. Beginning between 4-8 weeks after surgery, patients receive another 6
courses of FOLFOX, cetuximab, and bevacizumab as in neoadjuvant therapy.
After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for at least 3 years.
PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of metastatic colorectal cancer, meeting all of the following criteria:
- Metachronous or synchronous liver metastases
- Metastases potentially completely resectable
- No requirement for resection combined with cryotherapy or
radiofrequency ablation
- Must have undergone complete resection (R0) of the primary tumor within the past
4 weeks
- Measurable liver metastases
- No evidence of extrahepatic disease
- 1 or 2 resectable lung metastases allowed
PATIENT CHARACTERISTICS:
- WHO performance status 0-1
- Absolute neutrophil count > 1,500/mm³
- Platelet count > 100,000/mm³
- Hemoglobin > 9 g/dL
- WBC > 3,000/mm³
- Creatinine < 1.5 times upper limit of normal (ULN)
- Bilirubin < 1.5 times ULN
- AST and ALT < 5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No significant proteinuria (i.e., protein > 500 mg/24-hour urine collection)
- No known allergy to any of the study drugs (including excipients) or any related
compound, including hypersensitivity to Chinese hamster ovary cell products or other
recombinant human or humanized antibodies
- No bleeding diathesis or coagulopathy
- No peripheral neuropathy > grade 1
- No serious nonhealing wound, ulcer, or bone fracture
- No clinically significant cardiovascular disease, including any of the following:
- Uncontrolled hypertension
- New York Heart Association class II-IV congestive heart failure
- Unstable angina pectoris within the past 12 months
- Peripheral vascular disease ≥ grade 2
- Serious cardiac arrhythmia requiring medication
- Myocardial infarction within the past 12 months
- Cerebrovascular accident or transient ischemic attack within the past 12 months
- No symptomatic diverticulitis or known gastroduodenal ulceration
- No significant traumatic injury within the past 4 weeks
- No known alcohol or drug abuse
- No psychological, familial, social, or geographical condition that would preclude
study compliance
- No other significant disease that would preclude study participation
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior chemotherapy for metastatic disease
- At least 1 month since prior major surgical procedure or open biopsy
- More than 30 days since prior participation in another clinical study
- Prior adjuvant chemotherapy for primary cancer allowed provided the following
criteria are met:
- At least 12 months since prior oxaliplatin-containing adjuvant therapy
- No persistent neuropathy
- No prior therapy targeting the epidermal growth factor receptor or vascular
endothelial growth factor (VEGF)/VEGF receptor
- No concurrent regular use of acetylsalicylic acid (> 325 mg/day) or other
nonsteroidal anti-inflammatory drugs
- No concurrent full-dose anticoagulation
- No concurrent prophylactic hematopoietic growth factors
- No concurrent allopurinol
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response rate (preoperative response rate)
Safety Issue:
No
Principal Investigator
Bernard Nordlinger, MD
Investigator Affiliation:
Hopital Ambroise Pare
Authority:
United States: Federal Government
Study ID:
CDR0000530116
NCT ID:
NCT00438737
Start Date:
January 2007
Completion Date:
Related Keywords:
- Colorectal Cancer
- Metastatic Cancer
- liver metastases
- stage IV colon cancer
- stage IV rectal cancer
- recurrent colon cancer
- recurrent rectal cancer
- Colorectal Neoplasms
- Neoplasm Metastasis
- Neoplasms
- Neoplasms, Second Primary
- Liver Neoplasms
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