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

NCT ID: NCT00582660

Last Updated: 2017-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-12-31
• Study Completion Date: 2008-06-30

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.

Detailed Description

We propose to test the hypothesis that celecoxib, a specific inhibitor of cyclooxygenase -2 (COX-2), will effectively inhibit the enzymatic activity in all tissues sampled after oral administration of celecoxib for 7 days preoperatively. One hundred twenty patients (120) undergoing standard surgical resection for the treatment of primary colorectal adenomas or carcinomas would be randomized to celecoxib or placebo given for 7 days prior to operation. Peripheral blood will be drawn prior to drug or placebo administration, and then morning of operation. At the time of definitive resection of the specimen, normal intestinal mucosa and primary tumor would be harvested and immediately snap frozen at -80 degrees. Levels of COX-2 activity (prostaglandin production) as well as expression of COX-2 and other markers (matrix metalloproteinases(MMPs), tissue inhibitors of MMPs (TIMPs), cell adhesion and cell cycle control molecules will be evaluated in normal mucosa and primary tumor compared between celecoxib and placebo treated patients.

Conditions

Colorectal Adenoma; Colorectal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

study drug BID for 7 days before surgery

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

Group Type: ACTIVE_COMPARATOR

Celecoxib

Intervention Type: DRUG

400 mg twice a day for 7 days prior to surgery

Placebo for 7 days before surgery

Placebo in a one to one randomization prior to surgery

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Celecoxib

400 mg twice a day for 7 days prior to surgery

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

study drug

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Patient must be undergoing colo-rectal resection

3. age > 18yrs

4. Karnofsky performance status(KPS) > 60.

5. Signed and dated informed consent.

6. Complete history and physical examination within 30 days of study entry.

7. 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).

8. Chest x-ray within 30 days of study entry.

9. 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.

Exclusion Criteria

1. severe infection ;White Blood Cell Count(WBC) > 2 times normal, fever, sepsis)

2. immunosuppression (steroids, transplant patient)

3. emergent operation(perforation, obstruction).

4. Patients with serum bilirubin or creatinine levels greater than two times the normal upper limit would be excluded.

5. Pregnant or lactating women or subjects of child bearing age who do not practice effective means of birth control

6. Sulfonamide allergy

7. 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.

1. 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.

2. 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.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Pharmacia

INDUSTRY

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Marty Heslin

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Martin J Heslin, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

Other Identifiers

NQ8-00-02-008

Identifier Type: OTHER

Identifier Source: secondary_id

F001228004

Identifier Type: -

Identifier Source: org_study_id