BAY 43-9006 Plus Cetuximab to Treat Colorectal Cancer
This study is currently recruiting participants.
Verified May 2012 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
First received: May 16, 2006
Last updated: May 14, 2013
Last verified: May 2012
- Colorectal cancer (CRC) is a major public health problem in the U.S. and worldwide, and 5-year survival with widespread metastatic disease is less than 5%.
- Expression of epidermal growth factor (EGFR) or up-regulation of the gene occurs in the majority of CRC cases (60-80%).
- Therapies targeting EGFR, like cetuximab, have shown activity in the treatment of solid tumors like CRC.
- Cetuximab is FDA approved for the treatment of EGFR-expressing CRC, but clinical responses to cetuximab are seen in only 10% of EGFR-expressing CRC.
- One possible mechanism of resistance to cetuximab could be Ras mutations.
- Another major pathway implicated in colon carcinogenesis is the vascular endothelial growth factor (VEGF) pathway, which is involved in angiogenesis and is a validated target for therapy in CRC.
- BAY 43-9006 is both a Raf kinase inhibitor and an inhibitor of VEGF receptor (VEGFR2) tyrosine kinase.
- We hypothesize that the combined inhibition of EGFR, VEGFR2, and the Ras-Raf pathway will demonstrate promising clinical activity in CRC.
- To determine objective response rate and toxicity profile of combination of BAY 43-9006 and cetuximab in previously treated EGFR-expressing metastatic CRC.
- To evaluate BAY 43-9006 pharmacokinetics & pharmacogenomics (CYP3A4/5).
- To evaluate for this combination treatment pharmacodynamics, effect on tumor vascularity and effect on angiogenic cytokines.
- Adults with histologically or cytologically documented, measurable, EGFR-expressing metastatic CRC, which has recurred or progressed following at least one prior 5FU-based combination chemotherapy regimen administered for the treatment of metastatic disease.
- Patients must have one lesion amenable to biopsy.
- BAY 43-9006 will be administered 400 mg by mouth twice daily
- Cetuximab will be administered as 400 mg/m(2) loading dose (week 1) followed by 250 mg/m(2) IV weekly.
- If procedure may be performed safely, tumor biopsy will be obtained prior to treatment and after 4 weeks of treatment.
- Expression and activation (phosphorylation) of signaling pathway components potentially affected by this treatment will be assessed.
- DCE-MRI scan will be performed prior to treatment and after 8 weeks of treatment to evaluate tumor vascularity and metabolism.
- Patients will be evaluated for response every 8 weeks using the RECIST criteria.
- This trial uses a phase II optimal design targeting a response rate of 25%. Up to 66 patients may be treated.
Metastatic Colorectal Cancer
EGFR-Expressing Metastatic CRC
Drug: Sorafenib (Bay 43-9006)
Genetic: proteomic profiling
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of BAY 43-9006 (Sorafenib) in Combination With Cetuximab (Erbitux(Trademark)) in EGFR Expressing Metastatic Colorectal Cancer (CRC)|
Resource links provided by NLM:
U.S. FDA Resources
Further study details as provided by National Institutes of Health Clinical Center (CC):
Primary Outcome Measures:
- Response rate, safety, and toxicity measured by two sample t-test or Wilcoxon rank sum test. [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Progression-free survival measured by Kaplan-Meier curve. [ Designated as safety issue: No ]
|Study Start Date:||May 2006|
|Estimated Study Completion Date:||May 2014|
|Estimated Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Intervention Details:Show Detailed Description
Drug: Sorafenib (Bay 43-9006)
N/AGenetic: proteomic profiling
N/AOther: immunoenzyme technique
N/AOther: immunohistochemistry staining method
N/AOther: laboratory biomarker analysis
N/AOther: pharmacological study
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00326495
|Contact: Michelle Eugeni, R.N.||(301) firstname.lastname@example.org|
|Contact: Shivaani Kummar, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: Michelle Eugeni 301-402-9537 firstname.lastname@example.org|
Sponsors and Collaborators
|Principal Investigator:||Shivaani Kummar, M.D.||National Cancer Institute (NCI)|