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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01110785
First received: April 23, 2010
Last updated: September 16, 2013
Last verified: April 2011
  Purpose

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 Intervention Phase
Colorectal Cancer
Biological: panitumumab
Drug: simvastatin
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Masking: 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.

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity measured by NCICTC v 3.0 [ Designated as safety issue: Yes ]
  • Median and mean overall survival [ Designated as safety issue: No ]
  • Median and mean progression-free survival [ Designated as safety issue: No ]
  • Objective response rate [ Designated as safety issue: No ]
  • Correlation between skin toxicity and response to treatment [ Designated as safety issue: No ]
  • Serum cholesterol and subsequent treatment response [ Designated as safety issue: No ]
  • Correlation between PTEN, PIK3CA, b-raf, ERK, and MEK status and objective response rate [ Designated as safety issue: No ]
  • Correlation between single nucleotide polymorphisms and objective response rate [ Designated as safety issue: No ]
  • Correlation between proteomics and objective response rate [ Designated as safety issue: No ]

Estimated Enrollment: 46
Study Start Date: April 2010
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01110785

Locations
Netherlands
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      
Diaconessenhuis Leiden Recruiting
Leiden, Netherlands, 2334 CK
Contact: Contact Person    31-71-517-8178      
Leiden University Medical Center Recruiting
Leiden, Netherlands, 2333 ZA
Contact: Contact Person    31-71-526-3486      
Sponsors and Collaborators
Leiden University Medical Center
Investigators
Principal Investigator: Hans Gelderblom, MD, PhD Leiden University Medical Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01110785     History of Changes
Other Study ID Numbers: CDR0000671002, DUT-LUMC-30012009, EUDRACT-2009-014452-30, EU-21033, DUT-LUMC-RASTAT-P, NL-29611-058-09
Study First Received: April 23, 2010
Last Updated: September 16, 2013
Health Authority: Unspecified

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:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Simvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014