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

This study has been terminated.
(For scientific, logistic, and administrative reasons.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov Identifier:
NCT00087256
First received: July 8, 2004
Last updated: January 4, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: Celecoxib
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Celecoxib Polyp Prevention Trial in Participants With Resected Stage I Colon Cancer

Resource links provided by NLM:


Further study details as provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):

Primary Outcome Measures:
  • To determine whether celecoxib 400 mg bid for 3 years will decrease the incidence of adenomatous polyps of the colon and rectum in participants with Stage I adenocarcinoma of the colon. [ Time Frame: 60 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To access whether celecoxib will increase disease-free survival. [ Time Frame: 60 months ] [ Designated as safety issue: Yes ]
  • To access whether celecoxib therapy affects self-reported symptoms and health-related quality of life. [ Time Frame: 60 months ] [ Designated as safety issue: No ]
  • To describe the quality of life in early stage colon cancer patients. [ Time Frame: 42 months ] [ Designated as safety issue: No ]
  • To evaluate if the benefits from celecoxib are more pronounced in a cohort of participants whose primary colon tumors and polyps express COX-2. [ Time Frame: 60 months ] [ Designated as safety issue: Yes ]
  • To examine the expression of signaling targets such as serine/threonine kinase (AKT) extracellular signal-regulated kinase (ERK2), and endoplasmic reticulum Ca2+-ATPases in the index tumor and polyps. [ Time Frame: 60 months ] [ Designated as safety issue: Yes ]
  • To monitor the toxicity and safety of celecoxib in this population. [ Time Frame: 60 months ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: July 2004
Study Completion Date: April 2006
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm 1: placebo
one placebo capsule taken orally twice a day for 3 years
Drug: Celecoxib
Other Name: Celebrex
Experimental: Arm 2: celecoxib
one 400 mg capsule taken orally twice a day for 3 years
Other: placebo

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00087256

Locations
United States, Pennsylvania
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15215
Sponsors and Collaborators
National Surgical Adjuvant Breast and Bowel Project (NSABP)
Investigators
Principal Investigator: Norman Wolmark, MD NSABP Foundation, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: National Surgical Adjuvant Breast and Bowel Project (NSABP)
ClinicalTrials.gov Identifier: NCT00087256     History of Changes
Other Study ID Numbers: NSABP P-3, NSABP-P-3
Study First Received: July 8, 2004
Last Updated: January 4, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Surgical Adjuvant Breast and Bowel Project (NSABP):
stage I colon cancer
adenocarcinoma of the colon

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Central Nervous System Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 26, 2014