Clinical trial NCT01190462: Cetuximab and Simvastatin in Treating Patients With Advanced or Metastatic Colorectal Cancer
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: recurrent colon cancer
stage III colon cancer
stage IV colon cancer
recurrent rectal cancer
stage III rectal cancer
stage IV rectal cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-08-27
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Percentage of patients free from progression and alive after 12.5 weeks following the first dose of treatment
Secondary outcomes:
measure: Correlation between overall response rate, progression-free survival, overall survival, and safety with skin toxicity and efficacy
Other outcomes:
Locations:
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis - locatie Langendijk
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: Leiden University Medical Center
name: Hans Gelderblom, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: