Cetuximab and Simvastatin in Treating Patients With Advanced or Metastatic Colorectal Cancer

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. Simvastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Simvastatin may help cetuximab work better by making tumor cells more sensitive to cetuximab. Giving cetuximab together with simvastatin may kill more tumor cells. PURPOSE: This phase II trial is studying giving cetuximab together with simvastatin in treating patients with advanced or metastatic colorectal cancer.

Detailed Description
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OBJECTIVES: Primary To determine the percentage of patients with k-ras mutant, advanced or metastatic colorectal cancer who are free from progression and alive after 12.5 weeks following the first dose of cetuximab in combination with simvastatin. Secondary To determine the correlation between overall response rate, progression-free survival, overall survival, and safety with skin toxicity and efficacy. To determine the predictive value of PTEN, PIK3CA, b-raf, and ERK and MEK status. (exploratory) To determine the predictive value of SNPs, proteomics, and circulating DNA. (exploratory) To evaluate cholesterol, proteomics, and circulating DNA as biomarkers in this setting. (exploratory) OUTLINE: This is a multicenter study. Patients receive cetuximab IV weekly and oral simvastatin once daily on days 1-7. Courses repeat every 7 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected for laboratory studies at baseline, during study, and after completion of study. After completion of study therapy, patients are followed up for 30 days.

Official Title
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Safety and Efficacy of the Addition of Simvastatin to Cetuximab in K-ras Mutant Advanced or Metastatic Colorectal Cancer Patients. A Single-Arm, Multicenter, Phase II Study Using a Simon Two Stage Design.

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: simvastatin
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of advanced or metastatic colorectal cancer Progressive disease in the past 3 months Failed prior oxaliplatin-, fluorouracil (5-FU)-, and irinotecan-containing regimens AND have the presence of a k-ras mutation within codon 12, 13, or 61 PATIENT CHARACTERISTICS: WHO performance status 0-2 Adequate organ function No history of toxicity during statin use No other malignancy within the past 5 years No history of severe pulmonary disease No clinically relevant coronary artery disease PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior epidermal growth factor receptor (EGFR)-targeting agents No concurrent verapamil or amiodarone

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: cetuximab|nan|
|Drug: simvastatin|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients free from progression and alive after 12.5 weeks following the first dose of treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between overall response rate, progression-free survival, overall survival, and safety with skin toxicity and efficacy |  |  | 

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