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

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.

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.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Biological: cetuximab; Drug: simvastatin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Breda, Netherlands, 4819 EV
    • Recruiting
    • Amphia Ziekenhuis - locatie Langendijk
    • Contact: Contact Person; Phone Number: 31-76-595-5000
  • Leiden, Netherlands, 2333 ZA
    • Recruiting
    • Leiden University Medical Center
    • Contact: Contact Person; Phone Number: 31-71-526-3486

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Percentage of patients free from progression and alive after 12.5 weeks following the first dose of treatment

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Investigators: Principal Investigator: Hans Gelderblom, MD, PhD, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Anticipated): August 1, 2012

Study Registration Dates

• First Submitted: August 26, 2010
• First Submitted That Met QC Criteria: August 26, 2010
• First Posted (Estimate): August 27, 2010

Study Record Updates

• Last Update Posted (Estimate): August 12, 2013
• Last Update Submitted That Met QC Criteria: August 9, 2013
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer; stage III colon cancer; stage III rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Cetuximab
• Other Study ID Numbers: DUT-LUMC-838; CDR0000683942 (Registry Identifier: PDQ (Physician Data Query)); NL-30642-058-10; EUDRACT-2009-017384-42; EU-21065