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Multicenter, Double-Blind, Placebo-Controlled Randomized Phase III Study of Adjuvant Therapy With Celecoxib in Combination With Chemotherapy in Patients With Curatively Resected Stage III Colon Cancer

Phase 3
18 Years
Open (Enrolling)
Colorectal Cancer

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Trial Information

Multicenter, Double-Blind, Placebo-Controlled Randomized Phase III Study of Adjuvant Therapy With Celecoxib in Combination With Chemotherapy in Patients With Curatively Resected Stage III Colon Cancer



- Compare disease-free survival of patients with curatively resected stage III
adenocarcinoma of the colon treated with adjuvant fluorouracil and leucovorin calcium
with or without celecoxib.


- Compare the overall survival, the occurrence of new primary colon cancer, and the
development of new polyps in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to ≥ 4 tumor-positive lymph nodes (yes vs no), form of adjuvant
chemotherapy (infusional vs bolus), low-dose aspirin for cardiovascular prophylaxis (yes vs
no), and participating center. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive fluorouracil and leucovorin calcium IV for up to 6 courses in
the absence of disease recurrence or unacceptable toxicity. Patients also receive oral
celecoxib twice daily.

- Arm II: Patients receive oral placebo twice daily and fluorouracil and leucovorin
calcium as in arm I.

In both arms, treatment with celecoxib or placebo continues for 3 years in the absence of
disease recurrence or unacceptable toxicity.

Patients are followed annually for 2 years.

PROJECTED ACCRUAL: A total of 1,450 patients (725 per treatment arm) will be accrued for
this study within 2 years.

Inclusion Criteria


- Histologically confirmed adenocarcinoma of the colon

- 15 cm above anal verge

- Stage III disease (any pT, N1-2, M0)

- No rectal cancer

- Must have undergone curative radical resection (R0 resection) within the past 6 weeks



- 18 and over

Performance status

- WHO 0-1

Life expectancy

- Not specified


- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3


- AST ≤ 5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN


- Creatinine ≤ 1.5 times ULN


- None of the following conditions within the past 6 months:

- Myocardial infarction

- Unstable angina

- Symptomatic congestive heart failure

- Serious uncontrolled cardiac arrhythmia

- Cerebrovascular accident or transient ischemic attack

- Deep vein thrombosis

- Other significant thromboembolic event


- No pulmonary embolism within the past 6 months


- No active gastric or duodenal ulceration within the past year

- No gastrointestinal bleeding within the past year

- No partial or complete bowel obstruction

- No known chronic malabsorption

- No active inflammatory bowel disease or chronic diarrhea (more than 4 stools/day)


- Not pregnant or nursing

- Fertile patients must use effective contraception

- HIV negative

- No AIDS-related illness

- No prior hypersensitivity to fluorouracil, leucovorin calcium, celecoxib, other COX-2
inhibitors, NSAIDs, salicylates, or sulfonamides

- No other severe acute or chronic medical condition or laboratory abnormality that
would preclude study participation, study drug administration, or study results

- No psychological, familial, sociological, or geographical condition that would
preclude study compliance

- No concurrent active infection

- No other malignancy within the past 5 years except adequately treated carcinoma in
situ of the cervix or basal cell or squamous cell skin cancer


Biologic therapy

- No concurrent sargramostim (GM-CSF) or molgramostim


- Not specified

Endocrine therapy

- No more than 4 weeks of concurrent orally/nasally inhaled steroids over a 6-month

- Concurrent mometasone (or fluticasone) allowed if patients require ≥ 4 weeks of
inhaled steroid therapy

- At least 30 days since other prior steroids

- No concurrent hormonal therapy


- No concurrent radiotherapy


- See Disease Characteristics

- No prior total colectomy or other major surgery that would result in substantial
alteration in transit to absorption of oral medication


- More than 30 days since prior investigational medication

- No prior systemic anticancer treatment for colon cancer

- No concurrent prophylactic fluconazole

- No concurrent lithium

- No concurrent chronic* use of full dose aspirin, nonsteroidal anti-inflammatory drugs
(NSAIDs), or cyclo-oxygenase-2 (COX-2) inhibitors

- Aspirin at cardioprotective doses (i.e., 80 mg daily or equivalent) allowed

- No concurrent participation in any other clinical study

- No other concurrent experimental agents (e.g., other COX-2 inhibitors, matrix
metalloproteinase inhibitors, inhibitors of the vascular endothelial growth
factor/Flk-1 pathway, or inhibitors of the epidermal growth factor receptor pathway)
NOTE: *Chronic use is defined as a frequency of 7 consecutive days (1 week) for more
than 3 weeks/year or more than 21 days throughout the year

Type of Study:


Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:

Disease-free survival as measured by Logrank every 3 months in year 1, every 6 months in years 2-3, and annually thereafter

Safety Issue:


Principal Investigator

Cornelis J.H. van de Velde, MD, PhD, FRCS, FRCPS

Investigator Affiliation:

Leiden University Medical Center


United States: Federal Government

Study ID:




Start Date:

March 2004

Completion Date:

Related Keywords:

  • Colorectal Cancer
  • adenocarcinoma of the colon
  • stage III colon cancer
  • Adenocarcinoma
  • Colonic Neoplasms
  • Colorectal Neoplasms