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.
18 Years
N/A
Both
Colorectal Cancer
Trial Information
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.
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Percentage of patients free from progression and alive after 12.5 weeks following the first dose of treatment
Safety Issue:
No
Principal Investigator
Hans Gelderblom, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Leiden University Medical Center
Authority:
Unspecified
Study ID:
CDR0000683942
NCT ID:
NCT01190462
Start Date:
August 2010
Completion Date:
Related Keywords:
- Colorectal Cancer
- recurrent colon cancer
- stage III colon cancer
- stage IV colon cancer
- recurrent rectal cancer
- stage III rectal cancer
- stage IV rectal cancer
- Colorectal Neoplasms
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