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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00305643
• Other study ID #: 2005-0328
• Secondary ID: MDA-CCC-0326MDA-
• Status: Terminated
• Phase: Phase 3
• First received: March 21, 2006
• Last updated: November 19, 2015
• Start date: February 2006
• Est. completion date: October 2008

Study information

• Verified date: November 2015
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 </= 2

6. 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

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Breast Cancer
• Colorectal Cancer
• Colorectal Neoplasms
• Pain

Intervention

Drug:
• Capecitabine
Initial dose of 750-1500 mg/m^2 orally twice a day for each 21 day cycle.
• Celecoxib
200 mg given orally twice a day for each 21 day cycle.

Procedure:
• Radiation Therapy
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.

Drug:
• Placebo
Oral placebo twice daily on days 1-21

Locations

Country	Name	City	State
Puerto Rico	MBCCOP - San Juan	San Juan
United States	CCOP - Columbus	Columbus	Ohio
United States	Hematology Oncology Associates of Central New York, PC - Northeast Center	East Syracuse	New York
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	CCOP - Greenville	Greenville	South Carolina
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	Cancer Research for the Ozarks	Springfield	Missouri
United States	CCOP - Northwest	Tacoma	Washington
United States	Scott and White Cancer Institute	Temple	Texas
United States	CCOP - Main Line Health	Wynnewood	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI), Pfizer

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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	No

External Links

•   Clinical trial summary, the National Cancer Institute's PDQ® database
•   UT MD Anderson Cancer Center website