Molecular Targeting of 15-Lipoxygenase-1 (15-LOX-1) for Apoptosis Induction in Human Colorectal Cancers - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00503035

Purpose

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).

Condition	Intervention	Phase
Familial Adenomatous Polyposis	Drug: Celecoxib Procedure: Colonoscopy Biopsy	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Molecular Targeting of 15-LOX-1 for Apoptosis Induction in Human Colorectal Cancers

Resource links provided by NLM:

Genetics Home Reference related topics: familial adenomatous polyposis Help Me Understand Genetics

MedlinePlus related topics: Cancer Colonoscopy Colorectal Cancer

Drug Information available for: Celecoxib

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

13-S-HODE, 15-LOX-1 primary product, levels (measured by ELISA assay) [ Time Frame: Baseline to post 6 months of celecoxib treatment ] [ Designated as safety issue: No ]
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).

Estimated Enrollment:	40
Study Start Date:	August 2003
Estimated Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Celecoxib 400 mg orally twice daily for 6 months	Drug: Celecoxib 400 mg by mouth twice daily x 6 months Other Names: Celebrex SC-58635 Procedure: Colonoscopy Biopsy Up to 23 additional colon tissue biopsies (the size of a pencil tip), additional 20 minutes on colonoscopy procedure

Detailed Description:

Celecoxib is a drug that was developed to treat arthritis. However, celecoxib may also help to stop or slow the growth of colon and rectal tumor cells.

At the start of the study, you will be asked questions about your medical history, have a complete physical exam, and have around 2 tablespoons of blood drawn for blood tests as part of your routine care for familial adenomatous polyposis. Also, blood tests such as fasting blood glucose and lipid profiling (cholesterol, LDL, HDL and triglyceride) will be assessed to determine eligibility. Women who are able to have children must have a negative blood pregnancy test within 14 days of starting celecoxib.

Before your scheduled colonoscopy, you will fill out a form asking about any medications and nutritional supplements that you are taking. In addition, you will be asked to complete a diet history. This will help researchers to evaluate patients' dietary habits. The questionnaire takes about 15 minutes to complete. You will also have around 1 teaspoon of blood drawn to measure the amount of celecoxib in your blood. Then, during your already scheduled colonoscopy procedure, you will have additional tissue biopsies (the size of a pencil tip) of your colon taken. For a colonoscopy procedure, a flexible tube with a light attached to the end is used to look inside your colon/lower gut. The biopsies will be taken through the flexible tube using a special cutting tool. Up to 23 biopsy samples may be taken. The biopsies should take about 20 extra minutes to complete.

After the procedure, you will start taking celecoxib by mouth once every 12 hours for 6 months. You will also have around 1 teaspoon of blood drawn to measure the amount of celecoxib in your blood at the completion of month 2 and 4 of celecoxib treatment. At the end of the 6 month treatment period, you will have another colonoscopy procedure. This is an additional procedure performed solely for this study and is not part of your standard of care for the treatment of familial adenomatous polyposis. A second set of biopsies will be taken (23 maximum). These biopsy samples will be studied and compared to the samples taken before treatment with celecoxib. You will also have around 1 teaspoon of blood drawn to measure the amount of celecoxib in your blood.

You will be contacted by phone 72 hours after your first dose of celecoxib and then every 2 weeks for the study to check for any side effects you may be experiencing.

The maximum amount of time you will remain on this study is 6 months. If at any time, you experience any intolerable side effects, you will be taken off the study.

This is an investigational study. Celecoxib is FDA approved and commercially available for familial adenomatous polyposis patients to reduce polyp formation. Up to 40 patients will take part in this study. All will be enrolled at M. D. Anderson.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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).
Adequate bone marrow function (ANC > 1500 ml, platelet count > 100,000/ml). Serum creatinine, total bilirubin, and ALT < 1.5 upper limit normal.
Over 16 years of age.
Patient is able to give an informed consent.
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:

Inflammatory bowel disease.
Intake of anti-inflammatory medications (e.g., non-steroidal, aspirin, and sulfasalazine) that cannot be discontinued starting 3 days prior to the enrollment.
Chemotherapy or radiation therapy in less than three months from the time of enrollment.
Individuals who are taking Coumadin that can not be discontinued starting 7 days prior to the enrollment.
Individuals who have received an investigational chemopreventive agent during the month prior to the biopsies.
History of bleeding diathesis.
History of sulfonamides (sulfa) allergies.
History of cardiovascular diseases that might include the following: myocardial infarction, angina, coronary angioplasty, congestive heart failure, stroke, or coronary bypass surgery.
Uncontrolled hypertension (> 135/> 85 mm Hg on three repeated measurements during the 6 weeks prior to enrollment on the study).
Diagnosis of diabetes.
Smoking history during the 6 months prior to enrollment on the study.
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.
Family history of premature coronary disease (i.e., onset < 55 years of age).
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).
History of deep venous thrombosis, pulmonary embolism, systemic lupus erythematous, family history of protein S or C deficiencies or prior heparin-induced thrombocytopenia.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00503035

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Imad Shureiqi, MD	M.D. Anderson Cancer Center
Study Chair:	Robert S. Bresalier, MD	UT MD Anderson Cancer Center
Study Chair:	Patrick Lynch, MD, JD	UT MD Anderson Cancer Center

More Information

Additional Information:

The University of Texas M.D.Anderson Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00503035 History of Changes
Obsolete Identifiers:	NCT00258219
Other Study ID Numbers:	DM02-592
Study First Received:	July 16, 2007
Last Updated:	November 10, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Familial Adenomatous Polyposis
Colorectal Tumors
Molecular Targeting
Celecoxib
Celebrex
SC-58635

Apoptosis Induction
Colon
Rectum
colonoscopy
Biopsy

Additional relevant MeSH terms:

Colorectal 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
Adenomatous Polyps
Adenoma
Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type
Colonic Neoplasms
Neoplastic Syndromes, Hereditary
Intestinal Polyposis
Genetic Diseases, Inborn
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on February 09, 2012