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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00227734
First received: September 26, 2005
Last updated: June 4, 2012
Last verified: June 2012
  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 and oxaliplatin + cetuximab
Drug: capecitabine and oxaliplatin
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

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 ]

Enrollment: 74
Study Start Date: June 2004
Study Completion Date: February 2006
Primary Completion Date: October 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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
Hirslanden Klinik Aarau
Aarau, Switzerland, CH-5001
Kantonspital Aarau
Aarau, Switzerland, 5001
Kantonsspital Baden
Baden, Switzerland, CH-5404
Praxis Dr. Streit
Baden, Switzerland, 5404
Universitaetsspital-Basel
Basel, Switzerland, CH-4031
Saint Claraspital AG
Basel, Switzerland, CH-4016
Inselspital Bern
Bern, Switzerland, CH-3010
Kantonsspital Bruderholz
Bruderholz, Switzerland, CH-4101
Spitaeler Chur AG
Chur, Switzerland, CH-7000
Hopital Cantonal Universitaire de Geneve
Geneva, Switzerland, CH-1211
Kantonsspital
Liestal, Switzerland, CH-4410
Ospedale Civico
Lugano, Switzerland, CH-6900
Praxis Dr. Beretta
Rheinfelden, Switzerland, 4310
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Regionalspital
Thun, Switzerland, 3600
City Hospital Triemli
Zurich, Switzerland, 8063
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Stadtspital Waid
Zurich, Switzerland, CH-8037
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
  More Information

Publications:
Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00227734     History of Changes
Other Study ID Numbers: SAKK 41/04, EU-20525
Study First Received: September 26, 2005
Last Updated: June 4, 2012
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Capecitabine
Cetuximab
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 15, 2014