Neoplasms

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Adenocarcinoma

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Hematinics

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Antirheumatic Agents

Analgesics

Liver Extracts

Sulindac

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Normal volunteers (or control group) enrolled with the only purpose to validate assays and the shipping method.

Placebo

Validate assays and shipping methods

Marybeth S Hughes, M.D.

Background:

- 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.

Objectives:

- To see if sulindac can improve treatment outcomes in people who are having surgery for advanced colorectal cancer.

Eligibility:

- Individuals at least 18 years of age who are having surgery for advanced colorectal cancer.

Design:

* 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.

* 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.

Surgery Plus Sulindac or Surgery Alone for Advanced Colorectal Cancer

Phase 2 Prospective Randomized Double Blind Trial Comparing Metastasectomy Plus Sulindac Versus Metastasectomy Alone in Patients With Stage IV Colorectal Cancer

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.

Charite University, Berlin, Germany

National Cancer Institute (NCI)

Principal Investigator

one tablet twice daily

Sulindac: one tablet twice daily

one tablet twice daily

Placebo: One tablet twice daily

Normal Volunteers (or Control Group)

Total

<=18 years

Between 18 and 65 years

>=65 years

Age, Categorical

Age, Continuous

Female

Male

Gender

Hispanic or Latino

Not Hispanic or Latino

Unknown or Not Reported

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

More than one race

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Marybeth Hughes

The trial was prematurely closed due to lack of accrual, thus the outcome measure was not met.

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.

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Surgery Plus Sulindac or Surgery Alone for Advanced Colorectal Cancer	NCT01856322	Colorectal Canc... Liver Metastasi... Colorectal Aden...	Sulindac Placebo Validate assays...	18 Years -	National Institutes of Health Clinical Center (CC)
Surgery Plus Sulindac or Surgery Alone for Advanced Colorectal Cancer	NCT01856322	Colorectal Canc... Liver Metastasi... Colorectal Aden...	Sulindac Placebo Validate assays...	18 Years -	National Institutes of Health Clinical Center (CC)
Surgery Plus Sulindac or Surgery Alone for Advanced Colorectal Cancer	NCT01856322	Colorectal Canc... Liver Metastasi... Colorectal Aden...	Sulindac Placebo Validate assays...	18 Years -	National Institutes of Health Clinical Center (CC)

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