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

NCT ID: NCT00227734

Last Updated: 2012-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-30
• Study Completion Date: 2006-02-28

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.

Detailed 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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

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

Group Type: ACTIVE_COMPARATOR

capecitabine and oxaliplatin

Intervention Type: DRUG

capecitabine and oxaliplatin without cetuximab

Arm II

Patients receive capecitabine and oxaliplatin as in arm I and cetuximab IV over 1-2 hours on days 1 and 8

Group Type: ACTIVE_COMPARATOR

capecitabine and oxaliplatin + cetuximab

Intervention Type: DRUG

cetuximab

Interventions

capecitabine and oxaliplatin + cetuximab

cetuximab

Intervention Type: DRUG

capecitabine and oxaliplatin

capecitabine and oxaliplatin without cetuximab

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Markus M. Borner, MD

Role: STUDY_CHAIR

Insel Gruppe AG, University Hospital Bern

Dieter Koeberle, MD

Role: PRINCIPAL_INVESTIGATOR

Cantonal Hospital of St. Gallen

Locations

Kantonspital Aarau

Aarau, , Switzerland

Hirslanden Klinik Aarau

Aarau, , Switzerland

Praxis Dr. Streit

Baden, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Saint Claraspital AG

Basel, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Inselspital Bern

Bern, , Switzerland

Kantonsspital Bruderholz

Bruderholz, , Switzerland

Spitaeler Chur AG

Chur, , Switzerland

Hopital Cantonal Universitaire de Geneve

Geneva, , Switzerland

Kantonsspital

Liestal, , Switzerland

Ospedale Civico

Lugano, , Switzerland

Praxis Dr. Beretta

Rheinfelden, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Regionalspital

Thun, , Switzerland

City Hospital Triemli

Zurich, , Switzerland

Stadtspital Waid

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Switzerland

References

Borner M, Koeberle D, Von Moos R, Saletti P, Rauch D, Hess V, Trojan A, Helbling D, Pestalozzi B, Caspar C, Ruhstaller T, Roth A, Kappeler A, Dietrich D, Lanz D, Mingrone W; Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland. Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK. Ann Oncol. 2008 Jul;19(7):1288-1292. doi: 10.1093/annonc/mdn058. Epub 2008 Mar 17.

Reference Type: RESULT

PMID: 18349029 (View on PubMed)

Other Identifiers

EU-20525

Identifier Type: -

Identifier Source: secondary_id

SAKK 41/04

Identifier Type: -

Identifier Source: org_study_id