Celecoxib in Preventing Polyps in Patients Who Have Undergone Surgery for Stage I Colon Cancer

National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP)

Status and phase

Terminated

Phase 3

Conditions

Colorectal Cancer

Treatments

Other: placebo

Drug: Celecoxib

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00087256

NSABP-P-3

NSABP P-3

Details and patient eligibility

About

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. It is not yet known whether celecoxib is effective in preventing polyps in patients with colon cancer.

PURPOSE: Randomized phase III trial to study the effectiveness of celecoxib in preventing the development of polyps in patients who have undergone surgery for stage I colon cancer.

Full description

OBJECTIVES:

Primary

Compare celecoxib vs placebo, in terms of decreasing the incidence of adenomatous polyps of the colon and rectum, in patients with resected stage I adenocarcinoma of the colon.

Secondary

Compare disease-free survival of patients treated with these regimens.
Compare the effect of these regimens on self-reported symptoms and health-related quality of life of these patients.
Compare the quality of life of patients treated with these regimens.
Compare the benefits of celecoxib in patients with primary tumors or polyps that express cyclo-oxygenase-2 (COX-2) with those that do not express COX-2.
Compare the expression of signaling targets such as serine/threonine AKT, extracellular signal-regulated kinase 2 (ERK2), and endoplasmic reticulum Ca+2- ATPases in the index tumor and polyps.
Determine the toxicity and safety of celecoxib in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to gender, tumor stage (T1 vs T2), age (≤ 49 vs 50 to 59 vs ≥ 60 years), and current aspirin use (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral celecoxib twice daily for 3 years.
Arm II: Patients receive oral placebo twice daily for 3 years. In both arms, treatment continues in the absence of unacceptable toxicity or the diagnosis of invasive colon cancer, carcinoma in situ of the colon or rectum, or a non-colon primary cancer.

Quality of life is assessed at baseline and then at 6, 12, 24, 36, and 42 months.

Patients are followed at 6 months and at 2 years.

PROJECTED ACCRUAL: A total of 1,200 patients (600 per treatment arm) will be accrued for this study within 2.5 years.

Enrollment

18 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the colon
- Stage I disease
- Distal border of tumor ≥ 12 cm from the anal verge
Tumor completely resected within the past 90 days
Must have undergone a preoperative or postoperative colonoscopy to the cecum (or small bowel anastomosis) within the past 90 days
- All observed polyps must have been removed
Patients with a history suggestive of hereditary non-polyposis colorectal cancer (HNPCC) must have a normal microsatellite instability status by immunohistochemistry or polymerase chain reaction
- Patients with family history of colon cancer who have not been diagnosed with HNPCC are eligible
No prior familial adenomatous polyposis
No prior invasive cancer or carcinoma in situ of the colon or rectum
No clinical or radiologic evidence of metastatic disease

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Zubrod 0-1

Life expectancy

At least 10 years

Hematopoietic

Complete blood count normal
Platelet count normal

Hepatic

Aspartate aminotransferase (AST) normal
Bilirubin normal
Alkaline phosphatase normal

Renal

Creatinine normal

Cardiovascular

No active ischemic heart disease
No New York Heart Association class III or IV heart disease
No myocardial infarction within the past 6 months
No symptomatic arrhythmia
No symptomatic peripheral vascular disease or carotid disease that would preclude study participation

Pulmonary

No aspirin-sensitive asthma

Gastrointestinal

No history of inflammatory bowel disease
No history of upper gastrointestinal bleeding
No history of duodenal or gastric ulcer

Other

No known hypersensitivity to any COX-2 inhibitor, NSAIDs, aspirin, or sulfonamides
No non-colorectal malignancy within the past 5 years except carcinoma in situ of the cervix, melanoma in situ, or basal cell or squamous cell skin cancer
No other disease that would preclude study participation
No psychiatric disorders, including history of clinical depression or addictive disorders, that would preclude giving informed consent or long-term compliance
No rheumatologic or skeletal disorders requiring chronic NSAIDs or steroid therapy
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

See Disease Characteristics

Other

No other concurrent investigational agents for colon cancer
No concurrent chronic use of other cyclo-oxygenase-2 (COX-2) inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), or salicylates (e.g., aspirin)
- Chronic use is defined as use for more than an average of 3 days per month
  - Concurrent NSAIDs allowed for up to 10 consecutive days for temporary relief due to inflammatory syndromes, injury, or postoperative pain
- Cardioprotective doses of aspirin (≤ 81 mg/day or 325 mg every other day) allowed
No concurrent fluconazole or lithium