Phase 2 Prospective Randomized Double Blind Trial Comparing Metastasectomy Plus Sulindac Versus Metastasectomy Alone in Patients With Stage IV Colorectal Cancer
- Despite strong evidence for a causative role of inflammatory mediators in intestinal
cancer, the underlying mechanisms remain obscure. Established evidence indicates
activation of the Wnt/beta-catenin pathway is an early step in the malignant
transformation of colorectal adenomas with persistent activation in 90% of colorectal
cancers. Activation of this pathway ultimately effects transcription of the S100A4
- S100A4 transcript serum levels have been shown to correlate with risk of recurrence in
colorectal cancer and patients with systemic metastases are found to have increased
S100A4 transcript expression.
- S100A4 may be a novel prognostic biomarker in colorectal cancer.
- Cyclooxygenase-2 is a key enzyme involved in the inflammatory response and is a key
target of molecular chemoprevention in colorectal adenoma prevention trials.
- Recent studies demonstrate mitigation of Wnt/beta-catenin signaling by COX-2 inhibition
via administration of the NSAID sulindac using in vitro and in vivo animal models.
- We hypothesize that sulindac administration will abrogate Wnt/beta-catenin mediated
signaling and thus decrease S100A4 activity in patients with colorectal metastases.
- We propose to define the benefit of sulindac administration to patients with colorectal
metastases following resection and validate the use of circulating S100A4 transcripts
as a novel biomarker for disease recurrence.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Determine if there is a difference in circulating S100A4 transcript in patients receiving sulindac 150 mgBD by mouth following resection of colorectal cancer metastases compared to those who do not. Patients will be randomized between two arms i...
Prakash K Pandalai, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|