Curcumin in Treating Patients With Familial Adenomatous Polyposis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00641147
First received: March 17, 2008
Last updated: July 20, 2016
Last verified: July 2016
  Purpose
This randomized phase II 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.

Condition Intervention Phase
Familial Adenomatous Polyposis
Drug: Curcumin
Other: Laboratory Biomarker Analysis
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Curcumin for Treatment of Intestinal Adenomas in Familial Adenomatous Polyposis (FAP)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Change in activation of NFKB pathway [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in Akt phosphorylation levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in apoptosis index levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in Ki-67 anti-proliferative cell nuclear antibody index levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in mucosa and adenoma histology assessed by light microscopy [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in mucosal DNA methylation levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in mucosal leukotriene levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in mucosal prostaglandin levels [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in ODC activity levels expressed as nmol of activity/mg of musosal tissue/hr [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in polyamines levels expressed pg/mg protein [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Change in vascular density [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]
  • Incidence of grade >= 2 adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
    A safety review will be performed at the time of interim analysis.

  • 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.

  • Medication compliance [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Number of patients failing study [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
  • Side effects of curcumin treatment [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Total number of polyps [ Time Frame: Up to 16 months ] [ Designated as safety issue: No ]
    The average number of polyps in the treatment groups will be compared by the t-test (or a distribution free analog if distribution assumptions are not met). Multivariate regression models will be used to adjust for strongly predictive factors that are not balanced in the treatment groups.


Estimated Enrollment: 50
Study Start Date: October 2010
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (curcumin)
Patients receive curcumin PO BID for 12 months.
Drug: Curcumin
Given PO
Other Names:
  • C.I. 75300
  • C.I. Natural Yellow 3
  • Diferuloylmethane
  • Turmeric Yellow
Other: Laboratory Biomarker Analysis
Correlative studies
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO BID for 12 months.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Detailed Description:

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 deoxyribonucleic acid (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 v-akt murine thymoma viral oncogene homolog 1 (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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. status/post (s/p) ileostomy

Exclusion Criteria:

  • Female patients of childbearing age not on effective birth control
  • Pregnant women
  • White blood cell count (WBC) < 3500/ml
  • Platelet count < 100,000/ml
  • Blood urea nitrogen (BUN) > 25mg%
  • Creatinine > 1.5mg%
  • Patients unable to stop non-steroidal anti-inflammatory drugs (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 gastroesophageal reflux disease (GERD) (symptomatic despite medication or current erosive esophagitis on endoscopy)
  • Patients with a history of peptic ulcer disease
  • Patients on warfarin or plavix
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00641147

Locations
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Francis Giardiello Johns Hopkins University/Sidney Kimmel Cancer Center
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00641147     History of Changes
Other Study ID Numbers: NCI-2013-00536  NCI-2013-00536  CDR0000592794  NA_00011821  00011821  1R01CA134620  R01CA134620  P30CA006973 
Study First Received: March 17, 2008
Last Updated: July 20, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Nasopharyngeal Neoplasms
Adenomatous Polyposis Coli
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Adenomatous Polyps
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplastic Syndromes, Hereditary
Intestinal Polyposis
Genetic Diseases, Inborn
Curcumin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on August 25, 2016