Celecoxib in Preventing Hand/Foot Syndrome Caused By Capecitabine With Metastatic Breast or Colorectal Cancer

OBJECTIVES:

- Determine the efficacy of celecoxib in reducing the incidence and severity of hand/foot
syndrome caused by capecitabine in patients with metastatic breast cancer or colorectal
cancer.

OUTLINE: This is a placebo-controlled, randomized, double-blind, multicenter study. Patients
are stratified according to metastatic disease (breast vs colorectal), ECOG performance
status (0 or 1 vs 2), prior chemotherapy (yes vs no).

Patients receive 1 of 2 treatment regimens.

- Regimen A (concurrent radiotherapy): Patients undergo radiotherapy 5 days a week for
5-6 weeks and receive oral capecitabine twice daily 5 days a week. Following completion
of radiotherapy, patients may continue oral capecitabine as in regimen B.

- Regimen B (no radiotherapy): Patients receive oral capecitabine once daily on days
1-14. Courses repeat every 21 days.

Patients are also randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral celecoxib twice daily on days 1-21.

- Arm II: Patients receive oral placebo twice daily on days 1-21. In both arms, treatment
repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 342 patients will be accrued for this study.

Inclusion Criteria:

1. Patients with metastatic colorectal cancer or breast cancer who are scheduled*** to
receive capecitabine with an initial dose in the range of 750-1500 mg/m2** twice
daily (total daily dose in the range of 1500-3000 mg/m2) alone or in combination with
one or more other agents. ***Patients may enter the study after having received
capecitabine for up to 21 days prior to study entry. **Doses may be rounded upward or
downward per physician discretion to utilize 500mg tablets.

2. Patients with either metastatic colorectal or metastatic breast cancer may have
received any number or type of prior treatment regimens for metastatic disease or
they may have received no prior treatment for metastatic disease.

3. Men and women from all ethnic and racial groups.

4. >/= 18 years old

5. Eastern Cooperative Oncology Group (ECOG) Performance Status
6. Adequate organ function: a. Total bilirubin limits (IUNL) b. aspartate aminotransferase (AST or SGOT) and alanine
aminotransferase (ALT or SGPT) and/or ALT(SGPT) < 5 * IUNL d. Alkaline phosphatase Clearance > 50 ml/min

7. Adequate bone marrow function: (a) Leukocytes >/= 3,000/microL; (b) Absolute
neutrophil count >/= 1,500/microL; (c) Platelets >/= 100,000/microL

8. Women of childbearing age and all men must agree to use adequate contraception
(hormonal or barrier method of birth control) prior to study entry and for the
duration of study participation.

9. Negative pregnancy test for women of childbearing age.

10. Must have the ability to understand and the willingness to provide a written informed
consent to participate in the study.

11. Controlled brain metastasis (i.e. stereotactic surgery, surgery steroids,
anticonvulsants).

Exclusion Criteria:

1. History of allergies to sulfonamide, aspirin, any NSAID (Nonsteroidal
anti-inflammatory drugs)or 5FU or any COX-2 inhibitor.

2. Any regular use of COX-2 inhibitors, NSAIDS or aspirin >325 mg more than twice a
week.

3. Pregnancy or lactation.

4. History of significant neurological or psychiatric disorders that would impede giving
consent, treatment or follow-up.

5. Any serious illness or medical condition: uncontrolled congestive heart failure,
uncontrolled hypertension or arrhythmia, active angina pectoris, any history of
myocardial infarction, stroke or transient ischemic attack (TIA).

6. Serious uncontrolled active infection.

7. Patients who cannot comply with taking and documenting oral study medications.

8. History of active peptic ulcer disease or upper gastrointestinal (GI) bleed within 12
months of enrollment.

9. Use of warfarin.

10. Patients with uncontrolled brain metastasis.

11. Patients may have had prior Hand-foot syndrome (HFS) but it must be completely
resolved for >/= 4 weeks.

12. No concurrent radiation therapy.