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.
18 Years
N/A
Both
Colorectal Cancer
Trial Information
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.
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- 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
PATIENT CHARACTERISTICS:
- 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
PRIOR CONCURRENT THERAPY:
- 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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Percentage of patients free from progression and alive at 11 weeks after the first dose of panitumumab measured by RECIST v 1.1
Safety Issue:
No
Principal Investigator
Hans Gelderblom, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Leiden University Medical Center
Authority:
Unspecified
Study ID:
CDR0000671002
NCT ID:
NCT01110785
Start Date:
April 2010
Completion Date:
Related Keywords:
- Colorectal Cancer
- recurrent colon cancer
- stage III colon cancer
- stage IV colon cancer
- recurrent rectal cancer
- stage III rectal cancer
- stage IV rectal cancer
- Colorectal Neoplasms
Name | Location |
|---|
