Surgery Plus Sulindac or Surgery Alone for Advanced Colorectal Cancer
|ClinicalTrials.gov Identifier: NCT01856322|
Recruitment Status : Terminated (The trial was prematurely closed due to lack of accrual.)
First Posted : May 17, 2013
Results First Posted : May 7, 2015
Last Update Posted : October 23, 2015
- Some types of inflammation may increase the risk of cancers in the intestinal track. Because of this possibility, anti-inflammatory drugs may be able to prevent tumor growth and spread. One such drug, sulindac, may be helpful to study. Researchers want to see if people who are having surgery to remove intestinal tumors from advanced colorectal cancer will benefit from sulindac. It will be tested against a placebo.
- To see if sulindac can improve treatment outcomes in people who are having surgery for advanced colorectal cancer.
- Individuals at least 18 years of age who are having surgery for advanced colorectal cancer.
- Participants will be screened with a physical exam and medical history. Blood samples will be collected. Imaging studies and heart and lung function tests may also be given.
- Participants will be separated into two groups. One group will take sulindac. The other will take a placebo.
- Participants will take sulindac or placebo twice daily from about 2 to 3 weeks before the scheduled surgery. Seven days before the surgery, they will stop taking the pills.
- Participants will have surgery to remove their tumors. The surgery will also remove affected organ tissue.
- Participants will start to take the pills again once they have recovered from surgery. They will continue taking the sulindac or placebo twice a day for 3 years, or for as long as the tumors do not return.
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer Liver Metastasis Colorectal Adenocarcinoma||Drug: Sulindac Drug: Placebo Other: Validate assays and shipping methods||Phase 2|
- 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 gene.
- 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 non-steroidal anti-inflammatory drug (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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Phase 2 Prospective Randomized Double Blind Trial Comparing Metastasectomy Plus Sulindac Versus Metastasectomy Alone in Patients With Stage IV Colorectal Cancer|
|Study Start Date :||April 2013|
|Primary Completion Date :||January 2015|
|Study Completion Date :||January 2015|
Active Comparator: Sulindac
one tablet twice daily
one tablet 150mg twice daily
Placebo Comparator: Placebo
one tablet twice daily
One tablet twice daily
Normal Volunteers (or control group)
Normal volunteers (or control group) enrolled with the only purpose to validate assays and the shipping method.
|Other: Validate assays and shipping methods|
- Difference in Circulating S100A4 Transcript in Patients Receiving Sulindac 150 mg BD (Twice Daily) by Mouth Following Resection of Colorectal Cancer Metastases Compared to Those Who do Not. [ Time Frame: 3 years ]Difference in circulating S100A4 transcript levels will be determined by assessing the circulating S100A4 transcript level at initial presentation versus the circulating S100A4 transcript level post resection.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01856322
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Marybeth S Hughes, M.D.||National Cancer Institute (NCI)|