Clinical trial NCT00305643: Celecoxib in Preventing Hand/Foot Syndrome Caused By Capecitabine With Metastatic Breast or Colorectal Cancer
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Breast Cancer
Colorectal Cancer
Pain
Keywords: Hand-Foot Syndrome
cancer-related problem/condition
drug/agent toxicity by tissue/organ
pain
palmar-plantar erythrodysesthesia
stage IV breast cancer
male breast cancer
recurrent breast cancer
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
Celecoxib
Celebrex
Capecitabine
Xeloda
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Pfizer
First posted: 2006-03-22
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility 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.

Primary outcomes:
measure: Incidence of Hand/Foot Syndrome (HFS) > Grade 1 at 16 Weeks Based on the CTC 3.0 Criteria.
timeFrame: At 16 Weeks, with evaluations and blood test every 3 weeks.
Secondary outcomes:
measure: Incidence of Hand/Foot Syndrome (HFS) > Grade 1 at 16 Weeks Based on WHO Criteria.
timeFrame: At 16 Weeks
Other outcomes:
Locations:
city: Santa Rosa
country: United States
facility: CCOP - Santa Rosa Memorial Hospital
state: California
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Springfield
country: United States
facility: Cancer Research for the Ozarks
state: Missouri
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of Central New York, PC - Northeast Center
state: New York
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Wynnewood
country: United States
facility: CCOP - Main Line Health
state: Pennsylvania
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Temple
country: United States
facility: Scott and White Cancer Institute
state: Texas
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: MBCCOP - San Juan
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Scott Kopetz, MD
role: PRINCIPAL_INVESTIGATOR
References: