NCT01110785

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

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.

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 46 (estimated)
• Sponsor: Leiden University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	panitumumab
DRUG	simvastatin
OTHER	laboratory biomarker analysis

Timeline

• Start date: 2010-04-01
• Primary completion: 2012-04-01
• First posted: 2010-04-27
• Last updated: 2013-09-17

Locations

4 sites across 1 country: Netherlands