Peripheral Neuropathy, Stage 0 Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage I Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage III Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer
Conditions
Brief summary
This pilot clinical trial studies how well ultrasound works in detecting taxane-induced neuropathy in patients with breast cancer. Ultrasound may work better in diagnosing and detecting neuropathy in breast cancer patients treated with the chemotherapy drug called a taxane.
Detailed description
PRIMARY OBJECTIVES: I. To compare tibial motor nerve ultrasound cross-sectional area (CSA) between taxane-induced peripheral neuropathy (TIPN) patients and historical data among healthy adults. SECONDARY OBJECTIVES: I. To compare sural sensory nerve ultrasound CSA between TIPN patients and historical data among healthy adults. II. To determine if the above changes in nerve CSA correlate with NCS changes in the same TIPN patients. III. To determine if the above changes in nerve CSA correlate with changes on a self-reported neuropathy scale (Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 \[QLQ-CIPN20\]) in the same TIPN patients. IV. To determine if the above changes in nerve CSA correlate with intraepidermal nerve fiber (IENF) density changes on skin biopsy in the same TIPN patients. TERTIARY OBJECTIVES: I. To assess activated mast cells in skin biopsies in TIPN patients in relation to severity of symptoms and above findings. II. To assess serum inflammatory markers in TIPN patients in relation to severity of symptoms and above findings. OUTLINE: Patients undergo peripheral nerve ultrasound. Patients also undergo skin biopsy. After completion of study, patients are followed up for 30 days.
Interventions
PROCEDUREBiopsy
Undergo skin biopsy
OTHERQuestionnaire Administration
Ancillary studies
DIAGNOSTIC_TESTUltrasound Tomography
Undergo peripheral nerve ultrasound
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Breast cancer (any stage) * Previously or currently receiving taxane-based chemotherapy * Clinical symptoms of peripheral neuropathy noted in medical record and suspected to be secondary to taxane-based therapy * Ability and willingness to understand and sign an informed consent
Exclusion criteria
* Self-reported or documented history of pre-existing peripheral neuropathy prior to initiation of taxane chemotherapy * Unable to provide history
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tibial Nerve Cross-sectional Area | Up to 30 days | Will be determined by ultrasound in the tibial nerve. Will be compared to the historical data from healthy patients using two-sample t-test (two-sample t-test selected as primary data from the historical control patients is available and will be used for analysis). Will also compare the nerve cross-sectional area in our study sample to that in the historical diabetic neuropathy patients and historical oxaliplatin neuropathy patients using one-sample t-test. The general linear model will be used to evaluate any factors (e.g., age) that may be associated with the nerve cross-sectional area. Due |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Amplitude of Nerve Response - Ankle | Up to 30 days | Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area (tibial cross-sectional area) and nerve conduction studies (amplitude of nerve response - ankle). |
| Conduction Velocity of Nerve Response - Tibial | Up to 30 days | Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area (tibial cross-sectional area) and nerve conduction studies (conduction velocity of nerve response - tibial). |
| Distal Latency of Nerve Response - Ankle | Up to 30 days | Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area (tibial cross-sectional area) and nerve conduction studies (distal latency of nerve response - ankle). |
| Self-reported Neuropathy Score | Up to 30 days | Will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20. Spearman's rank correlation coefficient will be used to examine the associations between the cross-sectional area and the self-reported neuropathy scale. |
| Sural Nerve Cross-sectional Area | Up to 30 days | Will be determined by ultrasound of the sural nerve. Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area and nerve conduction studies. The general linear model will be also used to evaluate the association after adjusting for one or two risk factors (e.g., age). Nerve cross-sectional area will be treated as the dependent variable. |
| Nerve Fiber Density in the Skin | Up to 30 days | Spearman's rank correlation coefficient will be used to examine the association between nerve cross-sectional area and distal intraepidermal nerve fiber density. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum Levels of Inflammatory Molecules | Up to 30 days | Spearman's rank correlation coefficient will be used to assess the associations between activated mast cells in skin biopsies, serum inflammatory markers, severity of symptoms, and primary outcome and secondary outcomes in taxane-induced peripheral neuropathy patients. |
| The Number of Activated Mast Cells | Up to 30 days | Spearman's rank correlation coefficient will be used to assess the associations between activated mast cells in skin biopsies, serum inflammatory markers, severity of symptoms, and primary outcome and secondary outcomes in taxane-induced peripheral neuropathy patients. |
Countries
United States
Participant flow
Pre-assignment details
Historical control information is a reference group only and were not active participants in this trial.
Participants by arm
| Arm | Count |
|---|---|
| Case Study sample | 20 |
| Case Study sample | 20 |
| Control (From Another Study) These patients were not enrolled as part of this study. This data comes from another study. Each of these n=60 patients had tests done on both left and right arms, which creates the n=120 samples found in the results. | 60 |
| Control (From Another Study) These patients were not enrolled as part of this study. This data comes from another study. Each of these n=60 patients had tests done on both left and right arms, which creates the n=120 samples found in the results. | 120 |
| Total | 220 |
Baseline characteristics
| Characteristic | Case | Control (From Another Study) | Total |
|---|---|---|---|
| Age, Continuous | 55.5 years | 45.9 years | 48.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 55 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 0 Participants | 6 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 | 2 Participants | 60 Participants | 62 Participants |
| Race (NIH/OMB) White | 12 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Female | 20 Participants | 38 Participants | 58 Participants |
| Sex: Female, Male Male | 0 Participants | 22 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 3 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Tibial Nerve Cross-sectional Area
Will be determined by ultrasound in the tibial nerve. Will be compared to the historical data from healthy patients using two-sample t-test (two-sample t-test selected as primary data from the historical control patients is available and will be used for analysis). Will also compare the nerve cross-sectional area in our study sample to that in the historical diabetic neuropathy patients and historical oxaliplatin neuropathy patients using one-sample t-test. The general linear model will be used to evaluate any factors (e.g., age) that may be associated with the nerve cross-sectional area. Due
Time frame: Up to 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Case | Tibial Nerve Cross-sectional Area | 13.0 mm^2 | Standard Deviation 3.6 |
| Control | Tibial Nerve Cross-sectional Area | 14.0 mm^2 | Standard Deviation 4.3 |
Secondary
Amplitude of Nerve Response - Ankle
Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area (tibial cross-sectional area) and nerve conduction studies (amplitude of nerve response - ankle).
Time frame: Up to 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Case | Amplitude of Nerve Response - Ankle | 0.15 Spearman correlation coefficient |
Secondary
Conduction Velocity of Nerve Response - Tibial
Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area (tibial cross-sectional area) and nerve conduction studies (conduction velocity of nerve response - tibial).
Time frame: Up to 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Case | Conduction Velocity of Nerve Response - Tibial | 0.15 Spearman correlation coefficient |
Secondary
Distal Latency of Nerve Response - Ankle
Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area (tibial cross-sectional area) and nerve conduction studies (distal latency of nerve response - ankle).
Time frame: Up to 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Case | Distal Latency of Nerve Response - Ankle | -0.23 Spearman correlation coefficient |
Secondary
Nerve Fiber Density in the Skin
Spearman's rank correlation coefficient will be used to examine the association between nerve cross-sectional area and distal intraepidermal nerve fiber density.
Time frame: Up to 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Case | Nerve Fiber Density in the Skin | -0.12 Spearman correlation coefficient |
Secondary
Self-reported Neuropathy Score
Will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20. Spearman's rank correlation coefficient will be used to examine the associations between the cross-sectional area and the self-reported neuropathy scale.
Time frame: Up to 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Case | Self-reported Neuropathy Score | -0.18 Spearman correlation coefficient |
Secondary
Sural Nerve Cross-sectional Area
Will be determined by ultrasound of the sural nerve. Spearman's rank correlation coefficient will be used to examine the associations between nerve cross-sectional area and nerve conduction studies. The general linear model will be also used to evaluate the association after adjusting for one or two risk factors (e.g., age). Nerve cross-sectional area will be treated as the dependent variable.
Time frame: Up to 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Case | Sural Nerve Cross-sectional Area | 0.30 Spearman correlation coefficient |
Other Pre-specified
Serum Levels of Inflammatory Molecules
Spearman's rank correlation coefficient will be used to assess the associations between activated mast cells in skin biopsies, serum inflammatory markers, severity of symptoms, and primary outcome and secondary outcomes in taxane-induced peripheral neuropathy patients.
Time frame: Up to 30 days
Other Pre-specified
The Number of Activated Mast Cells
Spearman's rank correlation coefficient will be used to assess the associations between activated mast cells in skin biopsies, serum inflammatory markers, severity of symptoms, and primary outcome and secondary outcomes in taxane-induced peripheral neuropathy patients.
Time frame: Up to 30 days