Nicotine Patches in Reducing Hand-Foot Syndrome in Patients Who Are Receiving Capecitabine For Metastatic Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Nicotine patches may reduce hand-foot syndrome in patients receiving capecitabine for metastatic breast cancer. It is not yet known which nicotine patch regimen may be more effective in reducing hand-foot syndrome. PURPOSE: This randomized clinical trial is studying which schedule of using nicotine patches is more effective in reducing hand-foot syndrome in patients who are receiving capecitabine for metastatic breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the feasibility of using nicotine patches, in terms of side effects and the number of voluntary withdrawals from the study, in patients with metastatic breast cancer undergoing chemotherapy with capecitabine. Secondary Determine the efficacy of nicotine patches as preventive agents for hand-foot syndrome (HFS) by assessing the incidence of HFS in each arm. Determine the grade of HFS in each arm. Determine the percentage of patients requiring a reduction in dose of capecitabine due to adverse events. Determine the percentage of patients requiring pain medication for HFS. Determine the percentage of patients using other symptomatic treatments for HFS (e.g., moisturizers, ice, cooling packs). Evaluate the effect of nicotine patches on quality-of-life of patients undergoing capecitabine chemotherapy. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. Patients receive oral capecitabine twice daily on days 1-7 and 15-21. Treatment with capecitabine repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Arm I: Patients apply a transdermal nicotine patch once every 24 hours beginning on 1 day prior to initiation of capecitabine and continuing until the end of capecitabine therapy in the absence of disease progression or unacceptable toxicity. Arm II: Patients apply a transdermal nicotine patch once every 24 hours beginning on day 1 of the course of chemotherapy following the appearance of hand-foot syndrome symptoms. Treatment continues until the end of capecitabine therapy in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, and at 3 and 12 weeks. Patients also complete a daily diary to document side effects and medication compliance. After completion of study therapy, patients are followed at 3 weeks.

Official Title
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Pilot Study of Nicotine Patches to Reduce Hand-Foot Syndrome Associated With Capecitabine Chemotherapy in Patients With Metastatic Breast Cancer

Conditions
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Breast Cancer, Chemotherapeutic Agent Toxicity, Palmar-plantar Erythrodysesthesia

Intervention / Treatment
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* Drug: Nicotine patch


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of breast cancer Metastatic disease Scheduled to begin treatment with capecitabine at the University of California, San Francisco (UCSF) Cancer Center, San Francisco General Hospital, or Cornell Medical Center No concurrent hand-foot syndrome (HFS) due to other medications Prior HFS due to other medications allowed provided that the symptoms have been completely resolved for ≥ 4 weeks prior to study entry Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after completion of study therapy Able to participate in study procedures and quality-of-life evaluations and willing to comply with study requirements Non-English speaking patients are allowed provided they demonstrate adequate understanding of the study rationale and procedures and can give voluntary consent with the aid of a translator No clinically significant cardiac or peripheral vascular disease or symptom, including any of the following: History of myocardial infarction Congestive heart failure Cardiac arrhythmias (including atrial fibrillation) Cardiac or vascular bypass Uncontrolled hypertension Unstable angina Undiagnosed arrhythmias or claudication No Alzheimer disease, Parkinson disease, or active psychiatric disease Not currently smoking Patients who are former smokers must have stopped smoking ≥ 6 months prior to study entry No known hypersensitivity to nicotine patches PRIOR CONCURRENT THERAPY: At least 6 months since prior and no other concurrent nicotine patches Prior chemotherapy allowed, except capecitabine for treatment of metastatic disease Concurrent other symptomatic treatment for hand-foot syndrome (HFS) (e.g., usual skin care, topical moisturizers, ice packs, pain medications) allowed No concurrent pyridoxine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Prior to initiation of capecitabine<br>Patients apply a transdermal nicotine patch once every 24 hours beginning 1 day prior to initiation of capecitabine and continuing until the end of capecitabine therapy in the absence of disease progression or unacceptable toxicity. | Drug: Nicotine patch<br>* Nicotine patch applied prior to and concurrently with capecitabine chemotherapy or beginning during the first course of capecitabine after the onset of hand-foot syndrome symptoms<br>|
| Experimental: Arm B: After hand-foot syndrome symptoms appear<br>Patients apply a transdermal nicotine patch once every 24 hours beginning with the course of chemotherapy initiated after hand-foot syndrome symptoms appear and continuing until the end of capecitabine therapy in the absence of disease progression or unacceptable toxicity. | Drug: Nicotine patch<br>* Nicotine patch applied prior to and concurrently with capecitabine chemotherapy or beginning during the first course of capecitabine after the onset of hand-foot syndrome symptoms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Developed Hand-foot Syndrome (HFS) by Toxicity Grade | Incidence and severity of hand-foot syndrome (HFS) developed during chemotherapy will be defined by using the grading system for HFS per the NCI Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 for all patients assigned who received at least 1 cycle of capecitabine. | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Side Effects of the Transdermal Nicotine Patch | Beginning from first capecitabine cycle following first use of nicotine patch up through final study visit after approximately 15 weeks of nicotine patch use. All toxicities will be graded and classified according to NCI CTCAE version 3.0. | Up to 15 weeks | 
| Compliance in Using the Transdermal Nicotine Patch as Measured by Patient Diary | Self-report diaries of patch use beginning from capecitabine cycle following first use of nicotine patch use up through 15 weeks of possible nicotine patch use. Compliance will be reported by category (Compliant, Not Compliant, No Diaries Returned) | up to 15 weeks | 
| Number of Patients Requiring Dose Reduction of Capecitabine | Determined by the number of patients who required a toxicity-related, dose reduction of capecitabine during active treatment at each cycle where a dose reduction occurred. | up to 24 weeks | 
| Number of Patients With Reported Use of Pain Medication for HFS | Determine the number of patients requiring pain medication for the management of symptomatic HFS | Until last dose of capecitabine treatment or HFS has resolved, approximately 1 year | 
| Number of Patients With Reported Use of Other Symptomatic Treatments for HFS | Determine the number of patients utilizing additional treatments for symptomatic HFS. Additional treatments may include moisturizers, ice, and/or cooling packs | Until last dose of capecitabine treatment or HFS has resolved, approximately 1 year | 
| Quality of Life as Measured by FACT-B Scale | The Functional Assessment of Cancer Therapy - Breast (FACT-B) scale is widely used to measure health-related quality of life in cancer patients. The FACT-B is a 44-item self-report instrument designed to measure multidimensional quality of life (QL) in patients with breast cancer, given at screening, week 9, and week 15 assessments during nicotine patch use. | Up to 15 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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palmar-plantar erythrodysesthesia, chemotherapeutic agent toxicity, stage IV breast cancer, recurrent breast cancer