Colorectal Cancer, Metastatic Cancer
Conditions
Keywords
recurrent rectal cancer, stage IV rectal cancer, recurrent colon cancer, stage IV colon cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum, liver metastases, lung metastases
Brief summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, irinotecan, fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab and cetuximab, 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. Giving combination chemotherapy together with monoclonal antibody therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with monoclonal antibody therapy works in treating patients with advanced colorectal cancer with liver metastases or lung metastases that are potentially removable by surgery.
Detailed description
OBJECTIVES: Primary * To determine the pathological complete response (CR) rate in resected patients assessed on lesions of less than or equal to 30 mm in size. Secondary * To determine the clinical CR rate in all patients. * To determine toxicity and tolerability of this regimen (pre- and postoperative toxicity). * To evaluate perioperative safety in these patients. * To determine disease-free survival (time to progression in unresected patients) and overall survival of the whole study population. * To determine resectability in these patients. * To evaluate markers that predict the occurrence of a pathological CR or a non-response in pathological material (resected liver metastasis) and biological material collected from these patients. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, and 29, oxaliplatin IV over 2 hours on days 1 and 15, irinotecan hydrochloride IV over 30 minutes on days 8 and 22, fluorouracil IV over 24 hours on days 1, 8, 15, and 22, leucovorin calcium IV on days 1, 8, 15, and 22, and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 5 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients who are able to undergo liver resection receive bevacizumab on day 1 only of course 3 and undergo liver resection 3 weeks after chemotherapy. Beginning 4 weeks after liver resection, patients receive 2 additional courses of chemotherapy as adjuvant therapy. Patients undergo tumor tissue and blood sample collection periodically for biological studies. Samples are analyzed for markers that predict the occurrence of a complete pathological response (pCR) or a non-response. After completion of study treatment, patients are followed every 3 months for the first 2 years and then every 6 months thereafter.
Interventions
BIOLOGICALbevacizumab
BIOLOGICALcetuximab
DRUGfluorouracil
DRUGirinotecan hydrochloride
DRUGleucovorin calcium
DRUGoxaliplatin
OTHERlaboratory biomarker analysis
PROCEDUREadjuvant therapy
PROCEDUREbiopsy
PROCEDUREconventional surgery
PROCEDUREneoadjuvant therapy
Sponsors
Centre Hospitalier Universitaire Vaudois
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion criteria: * Histologically confirmed metastatic colorectal adenocarcinoma * Bidimensionally measurable metastatic disease limited to the liver and considered curatively resectable after response to systemic therapy as assessed by a surgical board * Additional metastatic disease to the lungs consisting of no more than 3 potentially resectable lesions allowed * Must have at least one lesion of 30 mm or less
Exclusion criteria
* History or evidence upon physical examination of CNS disease unless adequately treated (e.g., uncontrolled seizure with standard medical therapy or history of stroke) PATIENT CHARACTERISTICS: Inclusion criteria: * Performance status ≤ 1 * Life expectancy \> 12 weeks * WBC ≥ 3,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Creatinine 1.25 x upper limit of normal (ULN) * Bilirubin 1.25 x ULN (1.5 x ULN if liver metastasis) * AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastasis) * Woman and men of childbearing age must use adequate contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological complete response rate of lesions of less than or equal to 30 mm in size assessed by pathologic examination in resected specimens | — |
Secondary
| Measure | Time frame |
|---|---|
| Response as assessed by NCIC criteria | — |
| Toxicity as assessed by NCIC criteria | — |
Countries
Switzerland
Outcome results
None listed