Cetuximab, Leucovorin, Oxaliplatin, and Fluorouracil With or Without Bevacizumab in Treating Patients With Resectable Liver Metastases From Colorectal Cancer

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Unknown status

CT.gov ID

NCT00438737

Collaborator

(none)

100

Enrollment

Location

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as cetuximab and bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.Drugs used in chemotherapy, such as leucovorin, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with combination chemotherapy and bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase II trial is studying the side effects and how well giving cetuximab together with leucovorin, oxaliplatin, and fluorouracil works with or without bevacizumab in treating patients with resectable liver metastases from colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic Cancer	Biological: bevacizumab Biological: cetuximab Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2007

Outcome Measures

Primary Outcome Measures

Response rate (preoperative response rate) []
Safety (rate of perioperative safety findings) []

Secondary Outcome Measures

Progression-free survival []
Pathological resection rate []
Overall survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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