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

• ClinicalTrials.gov Identifier: NCT00305643
• Recruitment Status: Terminated
• First Posted: March 22, 2006
• Results First Posted: December 24, 2015
• Last Update Posted: December 24, 2015
• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI); Pfizer
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Colorectal Cancer; Pain	Drug: Capecitabine; Drug: Celecoxib; Procedure: Radiation Therapy; Drug: Placebo	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• 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
• Study Start Date: February 2006
• Actual Primary Completion Date: October 2008
• Actual Study Completion Date: October 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm I: Celecoxib + Capecitabine; 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; Initial dose of 750-1500 mg/m^2 orally twice a day for each 21 day cycle.; Other Name: Xeloda; Drug: Celecoxib; 200 mg given orally twice a day for each 21 day cycle.; Other Name: Celebrex; 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.; Other Names: RT; XRT
Placebo Comparator: Arm II: Placebo + Capecitabine; Placebo with standard capecitabine treatment (Initial dose of 750-1500 mg/m^2 orally twice/day)	Drug: Capecitabine; Initial dose of 750-1500 mg/m^2 orally twice a day for each 21 day cycle.; Other Name: Xeloda; 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.; Other Names: RT; XRT; Drug: Placebo; Oral placebo twice daily on days 1-21

Outcome Measures

Primary Outcome Measures :

1. Incidence of Hand/Foot Syndrome (HFS) > Grade 1 at 16 Weeks Based on the CTC 3.0 Criteria. [ Time Frame: At 16 Weeks, with evaluations and blood test every 3 weeks. ]
   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.

Secondary Outcome Measures :

1. Incidence of Hand/Foot Syndrome (HFS) > Grade 1 at 16 Weeks Based on WHO Criteria. [ Time Frame: At 16 Weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

CCOP - Santa Rosa Memorial Hospital

Santa Rosa, California, United States, 95403

United States, Michigan

CCOP - Grand Rapids

Grand Rapids, Michigan, United States, 49503

CCOP - Kalamazoo

Kalamazoo, Michigan, United States, 49007-3731

United States, Missouri

CCOP - Kansas City

Kansas City, Missouri, United States, 64131

Cancer Research for the Ozarks

Springfield, Missouri, United States, 65804

United States, New York

Hematology Oncology Associates of Central New York, PC - Northeast Center

East Syracuse, New York, United States, 13057-4510

United States, Ohio

CCOP - Columbus

Columbus, Ohio, United States, 43215

United States, Pennsylvania

CCOP - Main Line Health

Wynnewood, Pennsylvania, United States, 19096

United States, South Carolina

CCOP - Greenville

Greenville, South Carolina, United States, 29615

United States, Texas

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States, 77030-4009

Scott and White Cancer Institute

Temple, Texas, United States, 76508

United States, Washington

CCOP - Northwest

Tacoma, Washington, United States, 98405-0986

United States, Wisconsin

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States, 54449

Puerto Rico

MBCCOP - San Juan

San Juan, Puerto Rico, 00936

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Pfizer

Investigators

• Principal Investigator: Scott Kopetz, MD; M.D. Anderson Cancer Center

More Information

Additional Information:

Clinical trial summary, the National Cancer Institute's PDQ&#174; database  UT MD Anderson Cancer Center website 

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00305643 History of Changes
• Other Study ID Numbers: 2005-0328; MDA-CCC-0326 ( Other Identifier: NCI ); MDA-2005-0328 ( Other Identifier: NCI ); CDR0000458042 ( Registry Identifier: NCI )
• First Posted: March 22, 2006
• Results First Posted: December 24, 2015
• Last Update Posted: December 24, 2015
• Last Verified: November 2015

Keywords provided by M.D. Anderson Cancer Center:

cancer-related problem/condition; stage IV breast cancer; male breast cancer; recurrent breast cancer; stage IV colon cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer; Capecitabine; Hand-Foot Syndrome; drug/agent toxicity by tissue/organ; pain; palmar-plantar erythrodysesthesia; Celecoxib; Celebrex; Xeloda

Additional relevant MeSH terms:

Breast Neoplasms; Colorectal Neoplasms; Neoplasms by Site; Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Colonic Diseases; Capecitabine; Breast Diseases; Skin Diseases; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Celecoxib; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors