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

NCT00503035 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: DM02-592NCI-2012-015221R01CA106577-01A1
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Familial Adenomatous Polyposis

Keywords

Familial Adenomatous Polyposis; Colorectal Tumors; Molecular Targeting; Celecoxib; Celebrex; SC-58635; Apoptosis Induction; Colon; Rectum; colonoscopy; Biopsy

Outcome Measures

Primary Outcomes (1)

• 13-HODE Colonic Tissue Levels

  13-HODE colonic tissue levels measured by Liquid chromatography and tandem mass spectrometry measurements (LC/MS/MS) in colorectal normal and polyp tissues

  Baseline to post 6 months of celecoxib treatment

Secondary Outcomes (1)

• PGE2 Colonic Tissue Levels

  at the baseline colonoscopy (or sigmoidoscopy in patients who had undergone colectomy) before the initiation of celecoxib, and the follow-up colonoscopy or sigmoidoscopy was performed after celecoxib treatment (month 6)

Study Arms (1)

Celecoxib

EXPERIMENTAL

Celecoxib 400 mg orally twice daily for 6 months. Up to 23 additional colon tissue biopsies (the size of a pencil tip), additional 20 minutes on colonoscopy procedure.

Drug: Celecoxib; Procedure: Colonoscopy Biopsy

Interventions

Celecoxib DRUG

400 mg by mouth twice daily x 6 months

Also known as: Celebrex, SC-58635

Celecoxib

Colonoscopy Biopsy PROCEDURE

Up to 23 additional colon tissue biopsies (the size of a pencil tip), additional 20 minutes on colonoscopy procedure

Celecoxib

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Lynch PM, Morris JS, Ross WA, Rodriguez-Bigas MA, Posadas J, Khalaf R, Weber DM, Sepeda VO, Levin B, Shureiqi I. Global quantitative assessment of the colorectal polyp burden in familial adenomatous polyposis by using a web-based tool. Gastrointest Endosc. 2013 Mar;77(3):455-63. doi: 10.1016/j.gie.2012.11.038. Epub 2013 Jan 18.

  PMID: 23332604 BACKGROUND

• Yang P, Zuo X, Advani S, Wei B, Malek J, Day RS, Shureiqi I. Celecoxib Colorectal Bioavailability and Chemopreventive Response in Patients with Familial Adenomatous Polyposis. Cancer Prev Res (Phila). 2022 Apr 1;15(4):217-223. doi: 10.1158/1940-6207.CAPR-21-0066.

  PMID: 34610992 BACKGROUND

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Adenomatous Polyposis Coli; Colorectal Neoplasms

Interventions

Celecoxib

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Rectal Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Imad Shureiqi, MD
• Organization: UT MD Anderson Cancer Center

ishureiqi@mdanderson.org

713-745-4929

Study Officials

• Imad Shureiqi, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

• Robert S. Bresalier, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

• Patrick Lynch, MD, JD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2007
• First Posted: July 18, 2007
• Study Start: August 20, 2003
• Primary Completion: April 2, 2021
• Study Completion: April 2, 2021
• Last Updated: February 13, 2023
• Results First Posted: February 13, 2023

Record last verified: 2023-01

Locations

US (1)