Molecular Targeting of 15-Lipoxygenase-1 (15-LOX-1) for Apoptosis Induction in Human Colorectal Cancers
Condition: Familial Adenomatous Polyposis
MeSH terms: Adenomatous Polyposis Coli
Intervention: Celecoxib; Colonoscopy Biopsy
Intervention description: 400 mg by mouth twice daily x 6 months; Up to 23 additional colon tissue biopsies (the size of a pencil tip), additional 20 minutes on colonoscopy procedure
Intervention MeSH terms: Celecoxib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Familial Adenomatous Polyposis; Colorectal Tumors; Molecular Targeting; Celecoxib; Celebrex; SC-58635; Apoptosis Induction; Colon; Rectum; colonoscopy; Biopsy

Summary:

      Primary Objective:

        -  To determine whether celecoxib downregulates GATA-6 expression to upregulate 15-LOX-1
           expression and induce apoptosis in human rectal tumors, researchers will measure GATA-6
           and 15-LOX-1 expression, 13-S-HODE levels, and apoptosis rates in normal and colorectal
           polyp epithelial tissues before and after 6 months of celecoxib treatment of patients
           with familial adenomatous polyposis (FAP).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of familial adenomatous polyposis (patients should have colorectal remnant
             that can be biopsied. Patients who have had total colorectal surgical resection are
             not eligible).

          2. Adequate bone marrow function (ANC > 1500 ml, platelet count > 100,000/ml). Serum
             creatinine, total bilirubin, and ALT < 1.5 upper limit normal.

          3. Over 16 years of age.

          4. Patient is able to give an informed consent.

          5. Women of childbearing potential (women are considered to be of childbearing potential
             unless they are at 2 or more years post-menopausal/or surgically sterile), must:

               -  Not be pregnant or lactating.

               -  use adequate contraceptive measures (abstinence, IUD, birth control pills, or
                  diaphragm or condom with spermicidal gel) starting with last menses and
                  throughout the study duration.

               -  Have a negative serum pregnancy test within 14 days of starting celecoxib.

        Exclusion Criteria:

          1. Inflammatory bowel disease.

          2. Intake of anti-inflammatory medications (e.g., non-steroidal, aspirin, and
             sulfasalazine) that cannot be discontinued starting 3 days prior to the enrollment.

          3. Chemotherapy or radiation therapy in less than three months from the time of
             enrollment.

          4. Individuals who are taking Coumadin that can not be discontinued starting 7 days prior
             to the enrollment.

          5. Individuals who have received an investigational chemopreventive agent during the
             month prior to the biopsies.

          6. History of bleeding diathesis.

          7. History of sulfonamides (sulfa) allergies.

          8. History of cardiovascular diseases that might include the following: myocardial
             infarction, angina, coronary angioplasty, congestive heart failure, stroke, or
             coronary bypass surgery.

          9. Uncontrolled hypertension (> 135/> 85 mm Hg on three repeated measurements during the
             6 weeks prior to enrollment on the study).

         10. Diagnosis of diabetes.

         11. Smoking history during the 6 months prior to enrollment on the study.

         12. Uncontrolled hypercholesteremia (low-density lipoprotein cholesterol (LDL-C) > 130).
             Hypercholesteremia needs to be controlled following the updated the National
             Cholesterol Education Program Adult Treatment Panel III Guidelines for at least 3
             months prior to enrollment on the study. Hypercholesteremia treatment needs to be
             continued during the enrollment on the protocol.

         13. Family history of premature coronary disease (i.e., onset < 55 years of age).

         14. Metabolic syndrome diagnosis in patients who are 30 years or older. (The diagnosis of
             metabolic syndrome is made when three or more of these risk factors are present):

               -  Waist circumference: Men > 102 cm (> 40 in); Women > 88 cm (> 35 in).
                  *Triglycerides = 150 mg/dl (= 1.69 mmol/L).

               -  High-density lipoprotein cholesterol (HDL-C): [Men < 40 mg/dl (< 1.03 mmol/L),
                  Women <50 mg/dl (< 1.29 mmol/L)].

               -  Blood pressure = 130/= 85 mm Hg.

               -  Fasting glucose = 110 mg/dl (= 6.1 mmol/L).

         15. History of deep venous thrombosis, pulmonary embolism, systemic lupus erythematous,
             family history of protein S or C deficiencies or prior heparin-induced
             thrombocytopenia.