Capecitabine and Oxaliplatin With or Without Cetuximab in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as 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. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving capecitabine and oxaliplatin together with cetuximab is more effective than capecitabine and oxaliplatin in treating colorectal cancer.
PURPOSE: This randomized phase II trial is studying how well giving capecitabine and oxaliplatin together with cetuximab works compared to capecitabine and oxaliplatin in treating patients with metastatic colorectal cancer that cannot be removed by surgery.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
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Compare the efficacy of capecitabine and oxaliplatin with vs without cetuximab in patients with epidermal growth factor receptor-positive metastatic unresectable colorectal cancer.
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Compare the objective response (complete and partial response) in patients treated with these regimens.
Secondary
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Compare the safety of these regimens in these patients.
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Compare the clinical benefit (complete response, partial response, or stable disease for at least 18 weeks) in patients treated with these regimens.
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Compare overall survival, time to progression, and time to treatment failure in patients treated with these regimens.
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to performance status (0 vs 1), type of metastases (synchronous vs metachronous), prior adjuvant chemotherapy (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.
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Arm I: Patients receive oral capecitabine twice daily on days 1-15 and oxaliplatin IV over 2 hours on day 1.
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Arm II: Patients receive capecitabine and oxaliplatin as in arm I and cetuximab IV over 1-2 hours on days 1 and 8.
In both arms, courses repeat every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients will be followed every 3 months for 1 year and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 74 patients (37 per treatment arm) will be accrued for this study within 1.5 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Arm I Patients receive oral capecitabine twice daily on days 1-15 and oxaliplatin IV over 2 hours on day 1. |
Drug: capecitabine and oxaliplatin
capecitabine and oxaliplatin without cetuximab
|
| Active Comparator: Arm II Patients receive capecitabine and oxaliplatin as in arm I and cetuximab IV over 1-2 hours on days 1 and 8 |
Drug: capecitabine and oxaliplatin + cetuximab
cetuximab
|
Outcome Measures
Primary Outcome Measures
- Objective response (complete response [CR] and partial response [PR]) measured after completion of study treatment []
Secondary Outcome Measures
- Clinical benefit (CR, PR, and stable disease [SD]) measured at 18 weeks after randomization []
- Time to progression []
- Overall survival []
- Time to treatment failure measured after completion of study treatment []
- Adverse drug reactions measured after completion of study treatment []
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Histologically or cytologically confirmed metastatic colorectal cancer
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Unresectable disease
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Primary tumor or metastases must be epidermal growth factor receptor-positive by immunohistochemistry
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Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by CT scan
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Measurable lesion must not be in a previously irradiated area
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No prior or current CNS metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- WHO 0-1
Life expectancy
- Not specified
Hematopoietic
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Absolute neutrophil count ≥ 1,500/mm^3
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Platelet count ≥ 100,000/mm^3
Hepatic
- Bilirubin normal
Renal
- Creatinine clearance > 50 ml/min
Cardiovascular
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No New York Heart Association class III or IV congestive heart failure
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No symptomatic coronary artery disease
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No uncontrolled cardiac arrhythmia
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No myocardial infarction within the past 12 months
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No other significant cardiac disease
Other
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Not pregnant or nursing
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Fertile patients must use effective contraception during and for 12 months after study participation
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Negative pregnancy test
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No peripheral neuropathy of any origin > grade 1 (e.g., alcohol or diabetes)
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No nausea, vomiting, or malabsorption syndrome that would preclude ingestion or absorption of oral medication
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No severe reaction attributed to fluoropyrimidine therapy
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No known hypersensitivity to fluorouracil or any other component of the trial drugs
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No known dihydropyrimidine dehydrogenase deficiency
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No other medical condition (e.g., uncontrolled diabetes or active autoimmune disease), geographical situation, or psychiatric disorder that would preclude study compliance
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No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
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No prior chemotherapy for advanced or metastatic cancer
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At least 6 months since prior adjuvant chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
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At least 30 days since prior experimental drugs
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No other concurrent experimental drugs
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No concurrent drugs that are contraindicated for use with the trial drugs
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No other concurrent anticancer therapy
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No concurrent sorivudine or any of its chemically-related analogues (e.g., lamivudine)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kantonspital Aarau | Aarau | Switzerland | 5001 | |
| 2 | Hirslanden Klinik Aarau | Aarau | Switzerland | CH-5001 | |
| 3 | Praxis Dr. Streit | Baden | Switzerland | 5404 | |
| 4 | Kantonsspital Baden | Baden | Switzerland | CH-5404 | |
| 5 | Saint Claraspital AG | Basel | Switzerland | CH-4016 | |
| 6 | Universitaetsspital-Basel | Basel | Switzerland | CH-4031 | |
| 7 | Inselspital Bern | Bern | Switzerland | CH-3010 | |
| 8 | Kantonsspital Bruderholz | Bruderholz | Switzerland | CH-4101 | |
| 9 | Spitaeler Chur AG | Chur | Switzerland | CH-7000 | |
| 10 | Hopital Cantonal Universitaire de Geneve | Geneva | Switzerland | CH-1211 | |
| 11 | Kantonsspital | Liestal | Switzerland | CH-4410 | |
| 12 | Ospedale Civico | Lugano | Switzerland | CH-6900 | |
| 13 | Praxis Dr. Beretta | Rheinfelden | Switzerland | 4310 | |
| 14 | Kantonsspital - St. Gallen | St. Gallen | Switzerland | CH-9007 | |
| 15 | Regionalspital | Thun | Switzerland | 3600 | |
| 16 | City Hospital Triemli | Zurich | Switzerland | 8063 | |
| 17 | Stadtspital Waid | Zurich | Switzerland | CH-8037 | |
| 18 | UniversitaetsSpital Zuerich | Zurich | Switzerland | CH-8091 |
Sponsors and Collaborators
- Swiss Group for Clinical Cancer Research
Investigators
- Study Chair: Markus M. Borner, MD, University Hospital Inselspital, Berne
- Principal Investigator: Dieter Koeberle, MD, Cantonal Hospital of St. Gallen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SAKK 41/04
- EU-20525