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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00227734
• Other study ID #: SAKK 41/04
• Secondary ID: EU-20525
• Status: Completed
• Phase: Phase 2
• First received: September 26, 2005
• Last updated: June 4, 2012
• Start date: June 2004
• Est. completion date: February 2006

Study information

• Verified date: June 2012
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: February 2006
• Est. primary completion date: October 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• capecitabine and oxaliplatin + cetuximab
cetuximab
• capecitabine and oxaliplatin
capecitabine and oxaliplatin without cetuximab

Locations

Country	Name	City	State
Switzerland	Hirslanden Klinik Aarau	Aarau
Switzerland	Kantonspital Aarau	Aarau
Switzerland	Kantonsspital Baden	Baden
Switzerland	Praxis Dr. Streit	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	St. Gallen
Switzerland	Regionalspital	Thun
Switzerland	City Hospital Triemli	Zurich
Switzerland	Stadtspital Waid	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

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 cetuxi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response (complete response [CR] and partial response [PR]) measured after completion of study treatment			No
Secondary	Clinical benefit (CR, PR, and stable disease [SD]) measured at 18 weeks after randomization			No
Secondary	Time to progression			No
Secondary	Overall survival			No
Secondary	Time to treatment failure measured after completion of study treatment			No
Secondary	Adverse drug reactions measured after completion of study treatment			Yes