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

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with capecitabine may kill more tumor cells. Celecoxib may prevent or lessen hand-foot syndrome caused by capecitabine. PURPOSE: This randomized phase III trial is studying how well celecoxib works in preventing hand/foot syndrome caused by capecitabine in patients with metastatic breast or colorectal cancer.

Detailed Description
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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.

Official Title
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A Multicenter Phase III Placebo-Controlled Trial of Celecoxib for Prevention of Capecitabine-Induced Palmar/Plantar (Hand/Foot) Syndrome in Patients With Metastatic Breast and Colorectal Cancer

Conditions
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Breast Cancer, Colorectal Cancer, Pain

Intervention / Treatment
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* Drug: Capecitabine
* Drug: Celecoxib
* Procedure: Radiation Therapy
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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. Men and women from all ethnic and racial groups. >/= 18 years old Eastern Cooperative Oncology Group (ECOG) Performance Status </= 2 Adequate organ function: a. Total bilirubin </= 1.5 * the institutional upper-normal limits (IUNL) b. aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) </= 2.5 * IUNL c. Patients with liver mets AST/(SGOT) and/or ALT(SGPT) < 5 * IUNL d. Alkaline phosphatase </= 5 * IUNL e. Creatinine Clearance > 50 ml/min Adequate bone marrow function: (a) Leukocytes >/= 3,000/microL; (b) Absolute neutrophil count >/= 1,500/microL; (c) Platelets >/= 100,000/microL 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. Negative pregnancy test for women of childbearing age. Must have the ability to understand and the willingness to provide a written informed consent to participate in the study. Controlled brain metastasis (i.e. stereotactic surgery, surgery steroids, anticonvulsants). Exclusion Criteria: History of allergies to sulfonamide, aspirin, any NSAID (Nonsteroidal anti-inflammatory drugs)or 5FU or any COX-2 inhibitor. Any regular use of COX-2 inhibitors, NSAIDS or aspirin >325 mg more than twice a week. Pregnancy or lactation. History of significant neurological or psychiatric disorders that would impede giving consent, treatment or follow-up. 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). Serious uncontrolled active infection. Patients who cannot comply with taking and documenting oral study medications. History of active peptic ulcer disease or upper gastrointestinal (GI) bleed within 12 months of enrollment. Use of warfarin. Patients with uncontrolled brain metastasis. Patients may have had prior Hand-foot syndrome (HFS) but it must be completely resolved for >/= 4 weeks. No concurrent radiation therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I: Celecoxib + Capecitabine<br>Celecoxib 200 mg given orally twice/day along with standard capecitabine treatment (Initial dose of 750-1500 mg/m^2 orally twice/day). | Drug: Capecitabine<br>* Initial dose of 750-1500 mg/m^2 orally twice a day for each 21 day cycle.<br>* Other names: Xeloda;Drug: Celecoxib<br>* 200 mg given orally twice a day for each 21 day cycle.<br>* Other names: Celebrex;Procedure: Radiation Therapy<br>* Some patients may undergo radiation therapy 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 once daily on days 1-14.<br>* Other names: XRT;|
| Placebo Comparator: Arm II: Placebo + Capecitabine<br>Placebo with standard capecitabine treatment (Initial dose of 750-1500 mg/m^2 orally twice/day) | Drug: Capecitabine<br>* Initial dose of 750-1500 mg/m^2 orally twice a day for each 21 day cycle.<br>* Other names: Xeloda;Procedure: Radiation Therapy<br>* Some patients may undergo radiation therapy 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 once daily on days 1-14.<br>* Other names: XRT;Drug: Placebo<br>* Oral placebo twice daily on days 1-21<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Hand/Foot Syndrome (HFS) > Grade 1 at 16 Weeks Based on the CTC 3.0 Criteria. | The primary classification of palmar planter erythrodysethesia according to National Cancer Institute Common Toxicity Criteria (CTC) 3.0 criteria used to determine the incidences of > grade 1 hand and foot syndrome (HFS) by 16 weeks from the commencement of therapy. | At 16 Weeks, with evaluations and blood test every 3 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Hand/Foot Syndrome (HFS) > Grade 1 at 16 Weeks Based on WHO Criteria. | A secondary classification of palmar planter erythrodysethesia according to World Health Organization (WHO) criteria will be used for determination of the incidences of > grade 1 HFS by 16 weeks from the commencement of therapy. | At 16 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, Hand-Foot Syndrome, cancer-related problem/condition, drug/agent toxicity by tissue/organ, pain, palmar-plantar erythrodysesthesia, male breast cancer, recurrent breast cancer, stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, Celecoxib, Celebrex, Capecitabine, Xeloda