Cetuximab and Capecitabine in Treating Patients With Metastatic Colorectal Cancer That Failed Irinotecan Treatment

Study Overview
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Brief Summary
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RATIONALE: 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 colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with capecitabine may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab together with capecitabine work in treating patients with metastatic colorectal cancer.

Detailed Description
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OBJECTIVES: Primary Determine the response rate in patients with metastatic colorectal cancer treated with cetuximab and capecitabine that progressed on prior fluoropyrimidine-containing therapy comprising irinotecan with or without oxaliplatin. Secondary To determine the progression-free survival and overall survival of patients treated with this regimen. To determine the tolerance to therapy in these patients. To assess biological correlates of response in available tissue biopsies and blood samples. OUTLINE: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor tissue and blood collection periodically for correlative studies. Samples are analyzed for expression of genes correlated with fluoropyrimidine responsiveness via quantitation RT-PCR; degree of expression of EGFR via immunohistochemistry; and expression pattern analysis via gene expression profiling and polymorphism. After completion of study treatment, patients are followed periodically.

Official Title
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CA225103: A Phase II Study of a Combination of Cetuximab and Capecitabine in Patients With Metastatic Colorectal Cancer After Progression on Previous Fluoropyrimidine Containing Therapy

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: capecitabine
* Genetic: gene expression analysis
* Genetic: microarray analysis
* Genetic: polymorphism analysis
* Genetic: reverse transcriptase-polymerase chain reaction
* Other: immunohistochemistry staining method


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of metastatic colorectal cancer Measurable disease Disease progression during prior fluoropyrimidine-containing therapy comprising irinotecan with or without oxaliplatin Received standard first- and second-line irinotecan and oxaliplatin-based therapy Patients who completed 1 prior treatment for metastatic disease but refused standard second-line therapy are eligible Patients who's disease progressed within 6 months of previous therapy are eligible EGFR negative patients allowed No untreated or uncontrolled brain metastasis PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/μL Platelet count ≥ 100,000/μL ALT ≤ 5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 5 times ULN Serum creatinine ≤ 1.5 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No serious intercurrent infections or medical problems No active or uncontrolled infections No significant history of uncontrolled cardiac disease, including any of the following: Uncontrolled hypertension Unstable angina Myocardial infarction within the past 6 months Uncontrolled congestive heart failure Cardiomyopathy with decreased ejection fraction No prior severe infusion reaction to a monoclonal antibody No known dihydropyrimidine dehydrogenase deficiency or evidence of past hypersensitivity to fluoropyrimidine PRIOR CONCURRENT THERAPY: See Disease Characteristics No more than 2 prior treatments for metastatic colorectal cancer More than 2 weeks since prior therapy Prior radiotherapy allowed if < 30% of bone marrow involvement No other concurrent investigational agents No concurrent highly active antiretroviral therapy for HIV-positive patients No prior therapy that specifically and directly targets the EGFR pathway

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Cetuximab 400mg/m2 IV on day 1 over 2 hours then 250 mg/m2 over 1 hour weekly + Xeloda(Capecitabine) 1000mg/m2 BID on days 1-14 repeated every 21 days. | Biological: cetuximab<br> <br> Drug: capecitabine<br> <br> Genetic: gene expression analysis<br> <br> Genetic: microarray analysis<br> <br> Genetic: polymorphism analysis<br> <br> Genetic: reverse transcriptase-polymerase chain reaction<br> <br> Other: immunohistochemistry staining method<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by spiral CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Assessment after every 2 cycles of treatment, up to 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer