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

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Palmar-plantar Erythrodysesthesia; Chemotherapeutic Agent Toxicity
• Intervention / Treatment: Drug: Nicotine patch

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Prior to initiation of capecitabine; 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; 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
Experimental: Arm B: After hand-foot syndrome symptoms appear; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2007
• Primary Completion (Actual): March 24, 2014
• Study Completion (Actual): March 24, 2018

Study Registration Dates

• First Submitted: September 10, 2008
• First Submitted That Met QC Criteria: September 10, 2008
• First Posted (Estimate): September 11, 2008

Study Record Updates

• Last Update Posted (Actual): October 5, 2020
• Last Update Submitted That Met QC Criteria: September 11, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; chemotherapeutic agent toxicity; palmar-plantar erythrodysesthesia
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Dermatitis; Drug-Related Side Effects and Adverse Reactions; Drug Eruptions; Drug Hypersensitivity; Breast Neoplasms; Hand-Foot Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 057514; ROCHE-UCSF-057514 (Other Identifier: University of California, San Francisco); NCI-2011-03236 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No