Breast Cancer, Chemotherapeutic Agent Toxicity, Palmar-plantar Erythrodysesthesia
Conditions
Keywords
palmar-plantar erythrodysesthesia, chemotherapeutic agent toxicity, stage IV breast cancer, recurrent breast cancer
Brief summary
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
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.
Interventions
DRUGNicotine 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
Sponsors
Hoffmann-La Roche
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Developed Hand-foot Syndrome (HFS) by Toxicity Grade | up to 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compliance in Using the Transdermal Nicotine Patch as Measured by Patient Diary | up to 15 weeks | 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) |
| Number of Patients Requiring Dose Reduction of Capecitabine | up to 24 weeks | 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. |
| Frequency of Side Effects of the Transdermal Nicotine Patch | Up to 15 weeks | 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. |
| Number of Patients With Reported Use of Other Symptomatic Treatments for HFS | Until last dose of capecitabine treatment or HFS has resolved, approximately 1 year | Determine the number of patients utilizing additional treatments for symptomatic HFS. Additional treatments may include moisturizers, ice, and/or cooling packs |
| Quality of Life as Measured by FACT-B Scale | Up to 15 weeks | 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. |
| Number of Patients With Reported Use of Pain Medication for HFS | Until last dose of capecitabine treatment or HFS has resolved, approximately 1 year | Determine the number of patients requiring pain medication for the management of symptomatic HFS |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 12 |
| 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. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Never began capecitabine | 1 | 0 |
| Overall Study | No HFS / Never Started Patch/ | 0 | 4 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Arm A: Prior to Initiation of Capecitabine | Arm B: After Hand-foot Syndrome Symptoms Appear | Total |
|---|---|---|---|
| Age, Customized 30-39 years old | 1 Participants | 1 Participants | 2 Participants |
| Age, Customized 40-49 years old | 4 Participants | 4 Participants | 8 Participants |
| Age, Customized 50-59 years old | 2 Participants | 0 Participants | 2 Participants |
| Age, Customized 60-69 years old | 5 Participants | 5 Participants | 10 Participants |
| Age, Customized 70-79 years old | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized 80-89 years old | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 12 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 10 Participants | 17 Participants |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 8 / 11 | 8 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
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.
Time frame: up to 24 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Prior to Initiation of Capecitabine | Number of Patients Who Developed Hand-foot Syndrome (HFS) by Toxicity Grade | Grade 1 HFS | 5 Participants |
| Arm A: Prior to Initiation of Capecitabine | Number of Patients Who Developed Hand-foot Syndrome (HFS) by Toxicity Grade | Grade 2 HFS | 5 Participants |
| Arm A: Prior to Initiation of Capecitabine | Number of Patients Who Developed Hand-foot Syndrome (HFS) by Toxicity Grade | Grade 3 HFS | 0 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients Who Developed Hand-foot Syndrome (HFS) by Toxicity Grade | Grade 1 HFS | 1 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients Who Developed Hand-foot Syndrome (HFS) by Toxicity Grade | Grade 2 HFS | 6 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients Who Developed Hand-foot Syndrome (HFS) by Toxicity Grade | Grade 3 HFS | 1 Participants |
Secondary
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)
Time frame: up to 15 weeks
Population: Only 2 patients returned the self-reported medication diaries
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Prior to Initiation of Capecitabine | Compliance in Using the Transdermal Nicotine Patch as Measured by Patient Diary | Compliant | 1 participants |
| Arm A: Prior to Initiation of Capecitabine | Compliance in Using the Transdermal Nicotine Patch as Measured by Patient Diary | Not Compliant | 0 participants |
| Arm A: Prior to Initiation of Capecitabine | Compliance in Using the Transdermal Nicotine Patch as Measured by Patient Diary | No Diaries Returned | 10 participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Compliance in Using the Transdermal Nicotine Patch as Measured by Patient Diary | Compliant | 1 participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Compliance in Using the Transdermal Nicotine Patch as Measured by Patient Diary | Not Compliant | 0 participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Compliance in Using the Transdermal Nicotine Patch as Measured by Patient Diary | No Diaries Returned | 10 participants |
Secondary
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.
Time frame: Up to 15 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 3 Headache | 0 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 2 Sleep Disturbance | 1 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Diarrhea | 2 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Rash (at patch site) | 2 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Dizziness | 1 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Constipation | 0 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Headache | 2 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Stomach Pain | 0 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 2 Dizziness | 1 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Irritability | 1 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 2 Diarrhea | 1 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Myalgia | 2 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Sleep Disturbance | 1 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Taste alteration | 1 Participants |
| Arm A: Prior to Initiation of Capecitabine | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Nausea | 4 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Taste alteration | 1 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Nausea | 5 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Diarrhea | 2 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 2 Diarrhea | 0 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Headache | 2 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 3 Headache | 1 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Dizziness | 2 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 2 Dizziness | 0 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Sleep Disturbance | 2 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 2 Sleep Disturbance | 0 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Rash (at patch site) | 2 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Constipation | 1 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Stomach Pain | 1 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Irritability | 1 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Frequency of Side Effects of the Transdermal Nicotine Patch | Grade 1 Myalgia | 1 Participants |
Secondary
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.
Time frame: up to 24 weeks
Population: No toxicities for dose reduction assessed at cycle 1. The maximum number of cycles where a dose reduction occurred was 8 for Arm A, and 5 for Arm B.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Prior to Initiation of Capecitabine | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 4 | 0 Participants |
| Arm A: Prior to Initiation of Capecitabine | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 6 | 0 Participants |
| Arm A: Prior to Initiation of Capecitabine | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 3 | 3 Participants |
| Arm A: Prior to Initiation of Capecitabine | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 7 | 1 Participants |
| Arm A: Prior to Initiation of Capecitabine | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 5 | 1 Participants |
| Arm A: Prior to Initiation of Capecitabine | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 8 | 1 Participants |
| Arm A: Prior to Initiation of Capecitabine | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 2 | 3 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 8 | NA Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 2 | 4 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 3 | 5 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 4 | 1 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 5 | 1 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 6 | NA Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients Requiring Dose Reduction of Capecitabine | Treatment Cycle 7 | NA Participants |
Secondary
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
Time frame: Until last dose of capecitabine treatment or HFS has resolved, approximately 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Prior to Initiation of Capecitabine | Number of Patients With Reported Use of Other Symptomatic Treatments for HFS | 5 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients With Reported Use of Other Symptomatic Treatments for HFS | 7 Participants |
Secondary
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
Time frame: Until last dose of capecitabine treatment or HFS has resolved, approximately 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: Prior to Initiation of Capecitabine | Number of Patients With Reported Use of Pain Medication for HFS | 6 Participants |
| Arm B: After Hand-foot Syndrome Symptoms Appear | Number of Patients With Reported Use of Pain Medication for HFS | 7 Participants |
Secondary
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.
Time frame: Up to 15 weeks
Population: Data for this endpoint was not collected