Familial Adenomatous PolyposisPhase 2NCT00503035
Molecular Targeting of 15-Lipoxygenase-1 (15-LOX-1) for Apoptosis Induction in Human Colorectal Cancers
A Phase 2 study testing Celecoxib and Colonoscopy Biopsy in people with Familial Adenomatous Polyposis, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Familial Adenomatous Polyposis
- What is being tested?
- Celecoxib and Colonoscopy Biopsy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Aug 2003to 2 Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: 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).
Read the 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.
- Conditions
- Familial Adenomatous Polyposis
- Being tested
- Celecoxib, Colonoscopy Biopsy
- Keywords
- Familial Adenomatous Polyposis, Colorectal Tumors, Molecular Targeting, Celecoxib, Celebrex, SC-58635, Apoptosis Induction, Colon, Rectum, colonoscopy, Biopsy
- Medical subject headings
- Adenomatous Polyposis Coli, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CelecoxibDrug
Also called Celebrex, SC-58635
400 mg by mouth twice daily x 6 months
Colonoscopy BiopsyProcedure or surgery
Up to 23 additional colon tissue biopsies (the size of a pencil tip), additional 20 minutes on colonoscopy procedure
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Celecoxib; Procedure: Colonoscopy Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline to post 6 months of celecoxib treatment
Secondary outcomes (1)
PGE2 Colonic Tissue Levels
PGE2 colonic tissue levels measured by Liquid chromatography and tandem mass spectrometry measurements (LC/MS/MS) in colorectal normal and polyp tissues
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2007 (estimated)
- Study start20 Aug 2003
- Primary completion2 Apr 2021
- Study completion2 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Familial Adenomatous PolyposisStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Imad Shureiqi, MD, Principal investigator, M.D. Anderson Cancer CenterRobert S. Bresalier, MD, Study chair, M.D. Anderson Cancer CenterPatrick Lynch, MD, JD, Study chair, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00503035
- Sponsor's protocol ID
- DM02-592
- Other IDs
- NCI-2012-01522, 1R01CA106577-01A1
- Status last verified
- Jan 2023
- First submitted
- 16 Jul 2007
- Last updated
- 13 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 23332604Yang 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.
PubMed 34610992
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Targeting of 15-LOX-1 for Apoptosis Induction in Human Colorectal Cancers
- ClinicalTrials.gov ID
- NCT00503035
- Acronym / sponsor ID
- DM02-592
- Conditions
- Familial Adenomatous Polyposis
- Keywords
- Familial Adenomatous Polyposis, Colorectal Tumors, Molecular Targeting, Celecoxib, Celebrex, SC-58635, Apoptosis Induction, Colon
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 20 Aug 2003 (actual)
- Primary completion
- 2 Apr 2021 (actual)
- Study completion
- 2 Apr 2021 (actual)
- First posted
- 18 Jul 2007 (estimated)
- Results
- Posted 13 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Celecoxib | Experimental | Drug: Celecoxib, Procedure: Colonoscopy BiopsyCelecoxib 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CelecoxibAlso: Celebrex, SC-58635400 mg by mouth twice daily x 6 months | Drug | Celecoxib |
| Colonoscopy BiopsyUp to 23 additional colon tissue biopsies (the size of a pencil tip), additional 20 minutes on colonoscopy procedure | Procedure or surgery | Celecoxib |
Primary outcome
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
1 secondary outcome
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23332604Lynch 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.
- Background: PubMed 34610992Yang 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.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Imad Shureiqi, MD principal investigator
M.D. Anderson Cancer Center
Robert S. Bresalier, MD study chair
M.D. Anderson Cancer Center
Patrick Lynch, MD, JD study chair
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Celecoxib and Colonoscopy Biopsy in people with Familial Adenomatous Polyposis, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
13-HODE Colonic Tissue Levels (time frame: Baseline to post 6 months of celecoxib treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00503035, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2023.