Simvastatin and Panitumumab in Treating Patients With Advanced or Metastatic Colorectal Cancer
Primary Purpose
Colorectal Cancer
Status
Unknown status
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
panitumumab
simvastatin
laboratory biomarker analysis
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring recurrent colon cancer, stage III colon cancer, stage IV colon cancer, recurrent rectal cancer, stage III rectal cancer, stage IV rectal cancer
Eligibility 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
Sites / Locations
- Reinier de Graaf Group - DelftRecruiting
- HagaZiekenhuis - Locatie LeyenburgRecruiting
- Leiden University Medical CenterRecruiting
- Diaconessenhuis LeidenRecruiting
Outcomes
Primary Outcome Measures
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
Toxicity measured by NCICTC v 3.0
Median and mean overall survival
Median and mean progression-free survival
Objective response rate
Correlation between skin toxicity and response to treatment
Serum cholesterol and subsequent treatment response
Correlation between PTEN, PIK3CA, b-raf, ERK, and MEK status and objective response rate
Correlation between single nucleotide polymorphisms and objective response rate
Correlation between proteomics and objective response rate
Full Information
NCT ID
NCT01110785
First Posted
April 23, 2010
Last Updated
September 16, 2013
Sponsor
Leiden University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT01110785
Brief Title
Simvastatin and Panitumumab in Treating Patients With Advanced or Metastatic Colorectal Cancer
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 Type
Interventional
2. Study Status
Record Verification Date
April 2011
Overall Recruitment Status
Unknown status
Study Start Date
April 2010 (undefined)
Primary Completion Date
April 2012 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Leiden University Medical Center
4. Oversight
5. Study Description
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
46 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
panitumumab
Intervention Type
Drug
Intervention Name(s)
simvastatin
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Toxicity measured by NCICTC v 3.0
Title
Median and mean overall survival
Title
Median and mean progression-free survival
Title
Objective response rate
Title
Correlation between skin toxicity and response to treatment
Title
Serum cholesterol and subsequent treatment response
Title
Correlation between PTEN, PIK3CA, b-raf, ERK, and MEK status and objective response rate
Title
Correlation between single nucleotide polymorphisms and objective response rate
Title
Correlation between proteomics and objective response rate
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans Gelderblom, MD, PhD
Organizational Affiliation
Leiden University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Reinier de Graaf Group - Delft
City
Delft
ZIP/Postal Code
2625 AD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
31-15-260-3060
Facility Name
HagaZiekenhuis - Locatie Leyenburg
City
Den Haag
ZIP/Postal Code
2545 CH
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
31-70-210-0000
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
31-71-526-3486
Facility Name
Diaconessenhuis Leiden
City
Leiden
ZIP/Postal Code
2334 CK
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Contact Person
Phone
31-71-517-8178
12. IPD Sharing Statement
Learn more about this trial
Simvastatin and Panitumumab in Treating Patients With Advanced or Metastatic Colorectal Cancer
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