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

Colorectal Cancer Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01190462
• Other study ID #: DUT-LUMC-838
• Secondary ID: CDR0000683942NL-
• Status: Recruiting
• Phase: Phase 2
• First received: August 26, 2010
• Last updated: August 9, 2013
• Start date: August 2010

Study information

• Verified date: April 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 51
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• cetuximab

Drug:
• simvastatin

Other:
• laboratory biomarker analysis

Locations

Country	Name	City	State
Netherlands	Amphia Ziekenhuis - locatie Langendijk	Breda
Netherlands	Leiden University Medical Center	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients free from progression and alive after 12.5 weeks following the first dose of treatment			No
Secondary	Correlation between overall response rate, progression-free survival, overall survival, and safety with skin toxicity and efficacy			Yes