Capecitabine and Oxaliplatin With or Without Cetuximab in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

Swiss Group for Clinical Cancer Research

Status and phase

Completed

Phase 2

Conditions

Colorectal Cancer

Treatments

Drug: capecitabine and oxaliplatin

Drug: capecitabine and oxaliplatin + cetuximab

Study type

Interventional

Funder types

Other

Identifiers

NCT00227734

SAKK 41/04

EU-20525

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

Compare the efficacy of capecitabine and oxaliplatin with vs without cetuximab in patients with epidermal growth factor receptor-positive metastatic unresectable colorectal cancer.
Compare the objective response (complete and partial response) in patients treated with these regimens.

Secondary

Compare the safety of these regimens in these patients.
Compare the clinical benefit (complete response, partial response, or stable disease for at least 18 weeks) in patients treated with these regimens.
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.

Arm I: Patients receive oral capecitabine twice daily on days 1-15 and oxaliplatin IV over 2 hours on day 1.
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.

Enrollment

74 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed metastatic colorectal cancer
- Unresectable disease
- Primary tumor or metastases must be epidermal growth factor receptor-positive by immunohistochemistry
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by CT scan
- Measurable lesion must not be in a previously irradiated area
No prior or current CNS metastases

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

WHO 0-1

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin normal

Renal

Creatinine clearance > 50 ml/min

Cardiovascular

No New York Heart Association class III or IV congestive heart failure
No symptomatic coronary artery disease
No uncontrolled cardiac arrhythmia
No myocardial infarction within the past 12 months
No other significant cardiac disease

Other

Not pregnant or nursing
Fertile patients must use effective contraception during and for 12 months after study participation
Negative pregnancy test
No peripheral neuropathy of any origin > grade 1 (e.g., alcohol or diabetes)
No nausea, vomiting, or malabsorption syndrome that would preclude ingestion or absorption of oral medication
No severe reaction attributed to fluoropyrimidine therapy
No known hypersensitivity to fluorouracil or any other component of the trial drugs
No known dihydropyrimidine dehydrogenase deficiency
No other medical condition (e.g., uncontrolled diabetes or active autoimmune disease), geographical situation, or psychiatric disorder that would preclude study compliance
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

No prior chemotherapy for advanced or metastatic cancer
At least 6 months since prior adjuvant chemotherapy

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

At least 30 days since prior experimental drugs
No other concurrent experimental drugs
No concurrent drugs that are contraindicated for use with the trial drugs
No other concurrent anticancer therapy
No concurrent sorivudine or any of its chemically-related analogues (e.g., lamivudine)