Evaluation of Surgically Resected Colorectal Adenomas and Carcinomas After 7 Days Pretreatment With Celecoxib

NCT00582660 | Completed Phase 2 Results DMC

• 2 other identifiers: F001228004NQ8-00-02-008
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess how effective celecoxib is in limiting production of a hormone, prostaglandin, in the subject's body. It is felt that this hormone is involved in the evolution of pre-cancerous growths in the colon to cancerous stage or in the progression of an existing cancer. To answer this question, some subjects are given the new investigational drug, and other subjects a placebo. A placebo is a capsule that contains inactive ingredients. Only by comparing the response of two subject groups, one receiving placebo (inactive), and one receiving celecoxib (active), will we be able to know whether or not celecoxib actually works. The outcome we are assessing is the hormone activity before and after celecoxib is given.

Conditions

Colorectal Adenoma; Colorectal Carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of Subjects Witha Change (IMPROVEMENT) in Colo-rectal Adenocarcinoma as Measured by Cyclooxygenase-2 Activity After 7 Days of Celecoxib

  The Colo-Rectal adenocarcinoma will be measured by cyclooxygenase-2(COX-2) activity at 7 days post baseline. Cox-2 activity is measured by assessing tumors and normal tissue using "Electron microscope and Tandem mass Spectrometry" methodology though the UAB shared Mass Spectrometry facility. Improvement was measured by 2-fold increase in COX-2 activity from baseline. The methodology used was High Performance Liquid Chromatography(HPLC). additional studies include expression of genes thought to be important in colorectal carcinogenesis: COX-1 and 2, MMP, 2 7, and 9, tissue inhibitor of metalloproteinases(TIMPs) 1 ans 2 and beta-catenin.

  baseline to 7 days

• Subjects With Positive Response 72 Hours After Administration of Study Treatment as Measured by Immunoblot

  At 72 hours after start of treatment, the number of subjects with immunoblot demonstrated a 1.5 to 2 fold increase in 15-LOX-1 protein expression in human colorectal adenocarcinoma cell line with epithelial morphology(HT-29) and dihydrolipoamide dehydrogenase(DLD)-1 cells.

  baseline to 72 hours

Study Arms (2)

study drug BID for 7 days before surgery

ACTIVE COMPARATOR

400 mg Celecoxib the study drug will be given for 7 days before surgery

Drug: Celecoxib

Placebo for 7 days before surgery

PLACEBO COMPARATOR

Placebo in a one to one randomization prior to surgery

Drug: Placebo

Interventions

Celecoxib DRUG

400 mg twice a day for 7 days prior to surgery

Also known as: study drug

study drug BID for 7 days before surgery

Placebo DRUG

one tablet of placebo will be given for 7 days prior to surgery

Placebo for 7 days before surgery

Eligibility Criteria

• Age: 19 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mass suspicious for carcinoma, clinical diagnosis of adenocarcinoma of the colon (to be histologically confirmed upon study entry) or an adenoma that is not removable by endoscopy.
• Patient must be undergoing colo-rectal resection
• age \> 18yrs
• Karnofsky performance status(KPS) \> 60.
• Signed and dated informed consent.
• Complete history and physical examination within 30 days of study entry.
• Laboratory evaluations within 30 days of study entry to include: Complete Blood Count(CBC) with differential and platelets, Blood Urea Nitrogen(BUN), creatinine, bilirubin, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase(SGPT), lactate dehydrogenase(LDH), alkaline phosphatase, total protein, albumin and carcinoembryonic antigen(CEA).
• Chest x-ray within 30 days of study entry.
• The subject has no other serious medical illness, other than that treated by this study, which would limit the ability of the patient to receive protocol therapy, or psychiatric condition which would prevent informed consent.

You may not qualify if:

• severe infection ;White Blood Cell Count(WBC) \> 2 times normal, fever, sepsis)
• immunosuppression (steroids, transplant patient)
• emergent operation(perforation, obstruction).
• Patients with serum bilirubin or creatinine levels greater than two times the normal upper limit would be excluded.
• Pregnant or lactating women or subjects of child bearing age who do not practice effective means of birth control
• Sulfonamide allergy
• Recurrent or previous history of known ischemic heart disease or thrombotic events as well as any angioplasty or cardiac by-pass procedures in the previous 12 months.
• Medications taken by the patient that are listed in section 9.0 of this protocol would be reviewed by the enlisting physician prior to entry into the study. Warfarin, aspirin and methotrexate would be stopped prior to protocol entry as these are stopped prior to any surgery. The most common of the listed medications would be ACE inhibitors and furosemide. The dose, schedule and indications of the medications would be reviewed with the patient and a decision regarding entry into the study would be made by the enlisting physician. Other less common medications will be similarly reviewed, however most had little or no clinical side effects despite potential biochemical interactions.
• Medications known to be COX inhibitors would have to be stopped prior to entry into the study. This would include any aspirin,nonsteroidal antiinflammatory drugs(NSAID) (ibuprofen, naproxen, rofecoxib, celecoxib, Mobic, etc) or over the counter cold medication that might contain these substances. A list of common over-the-counter medications that might contain such substances will be reviewed with the patient and if there are any questions after the study has begun, instructions to call before taking any medications will be given.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Pfizer: collaborator
• Pharmacia: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Celecoxib; Drug Evaluation

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; 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; Drug Development; Investigative Techniques; Evaluation Studies as Topic

Limitations and Caveats

The most prominent factor that limited enrollment was this period of time was at the point that the FDA released its finding about the possible cardiac risks associated with Rofecoxib (VIOXX).

Results Point of Contact

• Title: Martin J. Heslin M.D.
• Organization: University of Alabama at Birmingham

marty.heslin@ccc.uab.edu

205-975-0450

Study Officials

• Martin J Heslin, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: December 28, 2007
• Study Start: December 1, 2001
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: June 15, 2017
• Results First Posted: August 7, 2014

Record last verified: 2017-05

Locations

US (1)