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

January 18, 2023 updated by: M.D. Anderson Cancer Center

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Celecoxib
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
13-HODE Colonic Tissue Levels
Time Frame: Baseline to post 6 months of celecoxib treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
PGE2 Colonic Tissue Levels
Time Frame: 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)
PGE2 colonic tissue levels measured by Liquid chromatography and tandem mass spectrometry measurements (LC/MS/MS) in colorectal normal and polyp tissues
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Imad Shureiqi, MD, M.D. Anderson Cancer Center
  • Study Chair: Patrick Lynch, MD, JD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 20, 2003

Primary Completion (ACTUAL)

April 2, 2021

Study Completion (ACTUAL)

April 2, 2021

Study Registration Dates

First Submitted

July 16, 2007

First Submitted That Met QC Criteria

July 16, 2007

First Posted (ESTIMATE)

July 18, 2007

Study Record Updates

Last Update Posted (ACTUAL)

February 13, 2023

Last Update Submitted That Met QC Criteria

January 18, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DM02-592
  • NCI-2012-01522 (REGISTRY: NCI CTRP)
  • 1R01CA106577-01A1 (NIH)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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