Surgery Plus Sulindac or Surgery Alone for Advanced Colorectal Cancer
Condition: Colorectal Cancer; Liver Metastasis; Colorectal Adenocarcinoma
MeSH terms: Colorectal Neoplasms; Neoplasm Metastasis
Intervention: Sulindac; Placebo; Validate assays and shipping methods
Intervention description: one tablet 150mg twice daily; One tablet twice daily
Intervention MeSH terms: Sulindac
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Colorectal Cancer; Liver Metastasis; Sulindac

Summary:

      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.
    

Eligibility criteria:

        -INCLUSION CRITERIA

          1. Histologically confirmed colorectal adenocarcinoma with metastatic disease confined to
             the liver, or limited extrahepatic intra-abdominal disease Note: limited sites of
             disease include:

               -  porta hepatis lymph node metastases

               -  pelvic lymph node metastases (internal iliac, external iliac or obturator)

          2. Hepatic and intra-abdominal metastases must be measurable by computed tomography (CT),
             magnetic resonance imaging (MRI) and/or positron emission tomography (PET) scan

          3. Liver disease must be amenable to gross total resection (R0/R1) with adequate
             functional liver remnant which requires preservation of at least 2 contiguous hepatic
             segments with adequate inflow, outflow, and biliary drainage with a functional liver
             remnant (FLR) volume of more than 20% (for healthy liver)

          4. Greater than or equal to 18 years of age.

          5. Must be able to understand and sign the Informed Consent Documentation.

          6. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) less than or
             equal to 2.

          7. Life expectancy of greater than six months.

          8. Patients of both genders must be willing to practice birth control during and for one
             week after taking sulindac/placebo.

          9. Hematology:

               -  Absolute neutrophil count greater than 1500/mm^3 without the support of
                  Filgrastim.

               -  Platelet count greater than 75,000/mm^3.

               -  Hemoglobin greater than 8.0 g/dl.

         10. Chemistry:

               -  Serum creatinine less than or equal to 1.5 mg/dl unless the measured creatinine
                  clearance is greater than 60mL/min/1.73m^2.

               -  Total bilirubin less than or equal to 2 mg/dl, except for patients with diagnosis
                  of Gilberts disease or hepatic pedicle obstruction then total bilirubin must be
                  less than or equal to 5 mg/dl.

         11. International normalized ratio (INR) less than or equal to 1.8.

        INCLUSION CRITERIA for NORMAL VOLUNTEERS

          -  Age greater than 18

          -  Able to read and understand the informed consent

          -  No self-reported co morbidities of history of cancer

        EXCLUSION CRITERIA

          1. Women of child-bearing potential who are pregnant or breast feeding because of the
             potentially dangerous effects of the chemotherapy on the fetus or infant.

          2. Active systemic infections, coagulation disorders or other major medical illnesses
             precluding major surgery.

          3. Patients receiving warfarin anticoagulation, who cannot be transferred to other
             agents, such as low molecular weight heparins, anti-factor Xa (anti-Xa) agents, etc.

          4. Active bleeding disorders

          5. Patients with uncontrolled hypertension (would suggest: systolic blood pressure (SBP)>
             155, diastolic blood pressure (DBP)> 90), unstable coronary disease (unstable angina,
             evidence of congestive heart failure (CHF), or myocardial infarction (MI) within 6-12
             months of study)

          6. Childs B or C cirrhosis or with evidence of severe portal hypertension by history,
             endoscopy, or radiologic studies or with evidence of moderate to severe ascites.

          7. Prior history of gastrointestinal (GI) bleeding unrelated to a cancer diagnosis

             Note: Patients who have a normal upper and lower endoscopy may be enrolled at the
             discretion of the principal investigator (PI).

          8. Renal insufficiency Discretion of principle investigator.