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

Inclusion 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 CT, MRI and/or 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 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/mm3 without the support of
Filgrastim.

- Platelet count greater than 75,000/mm3.

- 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/1.73m2.

- Total bilirubin less than or equal to 2 mg/dl, except for patients with
diagnosis of Gilbert's disease or hepatic pedicle obstruction then total
bilirubin must be less than or equal to 5 mg/dl.

11. 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-Xa agents, etc.

4. Active bleeding disorders

5. Patients with uncontrolled hypertension (would suggest: SBP> 155, DBP> 90),
unstable coronary disease (unstable angina, evidence of CHF, or 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 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 PI.

8. Renal insufficiency Discretion of principle investigator.