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.
- 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
- To evaluate the objective response rate (based on RECIST criteria version 1.1) in these
- To evaluate the correlation between skin toxicity and anti-tumor response in these
- 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
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
Masking: Open Label, Primary Purpose: Treatment
Percentage of patients free from progression and alive at 11 weeks after the first dose of panitumumab measured by RECIST v 1.1
Hans Gelderblom, MD, PhD
Leiden University Medical Center