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

Sponsored by:	Swiss Group for Clinical Cancer Research
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00227734

Purpose

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	Intervention	Phase
Colorectal Cancer	Drug: capecitabine Drug: cetuximab Drug: oxaliplatin	Phase II

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Capecitabine Oxaliplatin Cetuximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	Capecitabine and Oxaliplatin Alone or in Combination With Cetuximab as First-Line Treatment for Metastatic EGFR-Positive Colorectal Cancer, A Randomized Multicenter Phase II Trial

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Objective response (complete response [CR] and partial response [PR]) measured after completion of study treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical benefit (CR, PR, and stable disease [SD]) measured at 18 weeks after randomization [ Designated as safety issue: No ]
Time to progression [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Time to treatment failure measured after completion of study treatment [ Designated as safety issue: No ]
Adverse drug reactions measured after completion of study treatment [ Designated as safety issue: Yes ]

Study Start Date:

June 2004

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00227734

Locations

Switzerland

Rheinfelden, Switzerland, 4310
City Hospital Triemli
Zurich, Switzerland, 8063
Hirslanden Klinik Aarau
Aarau, Switzerland, CH-5001
Hopital Cantonal Universitaire de Geneve
Geneva, Switzerland, CH-1211
Inselspital Bern
Bern, Switzerland, CH-3010
Kantonspital Aarau
Aarau, Switzerland, 5001
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Kantonsspital Baden
Baden, Switzerland, CH-5404
Kantonsspital Bruderholz
Bruderholz, Switzerland, CH-4101
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Ospedale Civico
Lugano, Switzerland, CH-6900
Regionalspital
Thun, Switzerland, 3600
Saint Claraspital AG
Basel, Switzerland, CH-4016
Spitaeler Chur AG
Chur, Switzerland, CH-7000
Stadtspital Waid
Zurich, Switzerland, CH-8037

Baden, Switzerland, 5404
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Kantonsspital
Liestal, Switzerland, CH-4410

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

Study Chair:	Markus M. Borner, MD	University Hospital Inselspital, Berne
Investigator:	Dieter Koeberle, MD	Kantonsspital - St. Gallen

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications of Results:

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; for the 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 Mar 17; [Epub ahead of print]

Borner M, Mingrone W, Koeberle D, et al.: The impact of cetuximab on the capecitabine plus oxaliplatin (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC): a randomized phase II trial of the Swiss Group for Clinical Cancer Research (SAKK). [Abstract] J Clin Oncol 24 (Suppl 18): A-3551, 2006.

Study ID Numbers:	CDR0000445128, SWS-SAKK-41/04, EU-20525
Study First Received:	September 26, 2005
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00227734
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Study placed in the following topic categories:

Capecitabine
Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Cetuximab
Colonic Diseases
Intestinal Diseases
Rectal Diseases

Recurrence
Intestinal Neoplasms
Rectal neoplasm
Oxaliplatin
Digestive System Diseases
Gastrointestinal Neoplasms
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009