Curcumin in Treating Patients With Familial Adenomatous Polyposis

• Mean polyp size in mm (mean size of the 5 largest polyps) [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
  Continuous variables relating to colorectal proliferation and polyp size will be compared in the two treatment groups by parametric statistics.
• Number of patients failing study [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
• Ornithine decarboxylase activity expressed as nmol of activity/mg of musosal tissue/hr [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Ornithine decarboxylase activity expressed as nmol of activity/mg of musosal tissue/hr [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Polyamines expressed pg/mg protein [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Polyamines expressed pg/mg protein [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Mucosal DNA methylation [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Mucosal DNA methylation [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Ki-67 anti-proliferative cell nuclear antibody index [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Ki-67 anti-proliferative cell nuclear antibody index [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Apoptosis index [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Apoptosis index [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Vascular density [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Vascular density [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Mucosal prostaglandin levels [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Mucosal prostaglandin levels [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Mucosal leukotriene levels [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Mucosal leukotriene levels [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Mucosa and adenoma histology by light microscopy [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Mucosa and adenoma histology by light microscopy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Activation of NFKB pathway [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Activation of NFKB pathway [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Phosphorylation of Akt [ Time Frame: Baseline ] [ Designated as safety issue: No ]
• Phosphorylation of Akt [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Side effects of curcumin treatment [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
• Medication compliance [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

This clinical trial studies curcumin in treating patients with familial adenomatous polyposis. Curcumin may prevent colorectal cancer in patients with a history of rectal polyps or colorectal neoplasia

PRIMARY OBJECTIVES:

I. To determine in a randomized, double-blinded, placebo-controlled study the tolerability and effectiveness of curcumin to regress intestinal adenomas by measuring duodenal and colorectal/ileal polyp number, and polyp size in familial adenomatous polyposis patients with intact colons, ileorectal anastomosis surgery, or ileo-anal pullthrough (reservoir) surgery.

II. To measure markers of cell proliferation including colorectal mucosal levels of ornithine decarboxylase (ODC), polyamines, mucosal DNA methylation, proliferative index (Ki67 antiproliferative cell nuclear antibody), apoptosis index, vascular density, mucosal prostaglandin, leukotriene levels, and activation of the nuclear factor kappa B (NFKB), and Akt survival pathways.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive curcumin orally (PO) twice daily (BID) for 12 months.

ARM II: Patients receive placebo PO BID for 12 months.

After completion of study treatment, patients are followed up at 4 months.

• Drug: curcumin
  Given PO
  Other Names:

  • C.I. 75300
  • C.I. Natural Yellow 3
  • CU
  • Diferuloylmethane
• Other: placebo
  Given PO
  Other Name: PLCB
• Other: laboratory biomarker analysis
  Correlative studies

• Experimental: Arm I (curcumin)
  Patients receive curcumin PO BID for 12 months.
  Interventions:

  • Drug: curcumin
  • Other: laboratory biomarker analysis
• Placebo Comparator: Arm II (placebo)
  Patients receive placebo PO BID for 12 months.
  Interventions:

  • Other: placebo
  • Other: laboratory biomarker analysis

Inclusion Criteria:

• Patients with familial adenomatous polyposis who have undergone subtotal colectomy with ileorectal anastomosis, total coloctomy with ileo-anal pull through (reservoir), and patients with intact colons with 5 or more adenomas in the rectum-sigmoid or reservoir
• Patients with familial adenomatous polyposis (FAP) and duodenal adenomatous polyposis without current lower tract adenomatous polyposis i.e. s/p ileostomy

Exclusion Criteria:

• Female patients of childbearing age not on effective birth control
• Pregnant women
• WBC < 3500/ml
• Platelet count < 100,000/ml
• BUN > 25mg%
• Creatinine > 1.5mg%
• Patients unable to stop NSAIDS, aspirin, curcumin, tumeric, calcium, vitamin D, green tea, or polyphenol E supplements for the duration of the trial
• Malignancy other than nonmelanoma skin cancer
• Active bacterial infection
• Patients with symptoms of active GERD (symptomatic despite medication or current erosive esophagitis on endoscopy)
• Patients with a history of peptic ulcer disease
• Patients on Warfarin or Plavix