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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01110785
Recruitment Status : Unknown
Verified April 2011 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
First Posted : April 27, 2010
Last Update Posted : September 17, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Simvastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as panitumumab, 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. Giving simvastatin together with panitumumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well simvastatin given together with panitumumab works in treating patients with advanced or metastatic colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Biological: panitumumab Drug: simvastatin Other: laboratory biomarker analysis Phase 2

Detailed Description:



  • To determine if the proportion (at least 40%) of patients with K-ras mutant-type advanced or metastatic colorectal cancer are free from progression and alive based on RECIST criteria version 1.1 at 11 weeks after the first administration of panitumumab (i.e., 12.5 weeks after the scan at baseline at start of simvastatin).
  • To determine if these results are comparable with historical results of k-ras wild-type colorectal carcinoma patients treated with panitumumab.
  • To evaluate clinical signs of progression (according to RECIST criteria) in patients treated with this regimen.


  • To evaluate the safety of this regimen in these patients who have failed prior treatment with fluorouracil-, oxaliplatin-, and irinotecan-containing regimens.
  • To evaluate the overall survival of patients who are treated with this regimen and have failed prior fluorouracil-, oxaliplatin-, and irinotecan-containing regimens.
  • To evaluate the progression-free survival (based on RECIST criteria version 1.1) of these patients.
  • To evaluate the objective response rate (based on RECIST criteria version 1.1) in these patients.
  • To evaluate the correlation between skin toxicity and anti-tumor response in these patients.

Tertiary (exploratory)

  • To evaluate the role of serum cholesterol as a biomarker during treatment with panitumumab and simvastatin.
  • To correlate levels of serum cholesterol with treatment response and other factors, until progression of disease occurs.
  • To investigate whether PTEN, PIK3CA, b-raf, ERK, and MEK status correlate with response to panitumumab in these patients.
  • To investigate the role of single nucleotide polymorphisms related to the efficacy and metabolism of panitumumab as a predictor for response to panitumumab.
  • To investigate the role of proteomics (e.g., EGF) as potential predictive markers for response to panitumumab and as potential biomarkers during treatment with panitumumab.

OUTLINE: This is a multicenter study.

Patients receive oral simvastatin once daily on days 1-14 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for biomarker and other analyses.

After completion of study treatment, patients are followed for 30 days and then every 3 months thereafter.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of the Addition of Simvastatin to Panitumumab in K-ras Mutant Advanced or Metastatic Colorectal Cancer Patients. A Single-Arm, Multicenter, Phase II Study Using a Simon Two Stage Design.
Study Start Date : April 2010
Estimated Primary Completion Date : April 2012

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Percentage of patients free from progression and alive at 11 weeks after the first dose of panitumumab measured by RECIST v 1.1

Secondary Outcome Measures :
  1. Toxicity measured by NCICTC v 3.0
  2. Median and mean overall survival
  3. Median and mean progression-free survival
  4. Objective response rate
  5. Correlation between skin toxicity and response to treatment
  6. Serum cholesterol and subsequent treatment response
  7. Correlation between PTEN, PIK3CA, b-raf, ERK, and MEK status and objective response rate
  8. Correlation between single nucleotide polymorphisms and objective response rate
  9. Correlation between proteomics and objective response rate

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of colorectal cancer

    • Advanced or metastatic disease
  • Failed prior fluorouracil-, oxaliplatin- and irinotecan-containing regimens

    • In case of progressive disease within 6 months after start of adjuvant fluorouracil-, oxaliplatin-, and irinotecan-containing regimens, the adjuvant therapy is considered to be treatment for metastatic disease
  • Mutant-type k-ras status (mutation in codon 12, 13, or 61) on tumor material
  • Measurable disease according to RECIST criteria version 1.1
  • Progressive disease in the past 3 months according to RECIST criteria version 1.1
  • No symptomatic brain metastases, defined as any symptoms during the past 6 months


  • WHO performance status 0-2
  • WBC ≥ 2.0 x 10^9/L
  • ANC ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Hemoglobin ≥ 9 g/dL
  • Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST/ALT ≤ 3 times ULN (≤ 5 times ULN in case of liver metastases)
  • Creatinine clearance ≥ 60 mL/min
  • Magnesium normal
  • Calcium normal
  • Creatine phosphokinase ≤ 2.5 times ULN
  • Not pregnant or nursing
  • Not planning to become pregnant within 6 months after the end of study treatment
  • Fertile patients must use highly effective contraception during and for 6 months after completion of study therapy
  • No noncompliance in previous studies
  • No alcohol use > 4 units/day or unwilling to abstain from use
  • No history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or signs of interstitial lung disease on baseline CT scan
  • No clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, or serious uncontrolled cardiac arrhythmia) < 1 year prior to study
  • No symptomatic hypothyroidism
  • No history of toxicity during statin use


  • See Disease Characteristics
  • No prior EGFr-therapy, including monoclonal antibodies (e.g., panitumumab or cetuximab)
  • No concurrent verapamil, amiodarone, or dronedarone or unwilling to abstain from use

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01110785

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Reinier de Graaf Group - Delft Recruiting
Delft, Netherlands, 2625 AD
Contact: Contact Person    31-15-260-3060      
HagaZiekenhuis - Locatie Leyenburg Recruiting
Den Haag, Netherlands, 2545 CH
Contact: Contact Person    31-70-210-0000      
Leiden University Medical Center Recruiting
Leiden, Netherlands, 2333 ZA
Contact: Contact Person    31-71-526-3486      
Diaconessenhuis Leiden Recruiting
Leiden, Netherlands, 2334 CK
Contact: Contact Person    31-71-517-8178      
Sponsors and Collaborators
Leiden University Medical Center
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Principal Investigator: Hans Gelderblom, MD, PhD Leiden University Medical Center

Layout table for additonal information Identifier: NCT01110785     History of Changes
Other Study ID Numbers: CDR0000671002
First Posted: April 27, 2010    Key Record Dates
Last Update Posted: September 17, 2013
Last Verified: April 2011
Keywords provided by National Cancer Institute (NCI):
recurrent colon cancer
stage III colon cancer
stage IV colon cancer
recurrent rectal cancer
stage III rectal cancer
stage IV rectal cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Immunological
Antineoplastic Agents