Acupuncture in Reducing Chemotherapy-Induced Peripheral Neuropathy in Participants With Stage I-III Breast Cancer

Study Overview
=================
Brief Summary
-----------------
The goal of this study is to obtain preliminary evidence of the effect of 8 acupuncture treatments over 10 weeks in breast and GI cancer patients who are currently receiving or recently completed active neurotoxic chemotherapy and have clinically documented grade 1 or 2 neuropathy.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To obtain preliminary evidence of the clinical effects of acupuncture compared to usual care on the change in sensory neuropathic pain as measured by the European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Chemotherapy-Induced Peripheral Neuropathy (CIPN) 20 item (20) sensory subscale. SECONDARY OBJECTIVES: I. Change in the motor and autonomic neuropathic pain subscores on the EORTC QLQ-CIPN20. II. Change in patient-reported assessment of numbness and tingling using the 2-item Patient-Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) measure. III. Preventing the escalation of CIPN from grade 1 or 2 to a higher grade. IV. Amount and intensity of planned chemotherapy relative to completed chemotherapy. V. Effect on sensory and motor nerve function via nerve conduction studies (NCS) (e.g. conduction velocity, latency, and amplitude). VI. Effect on peripheral nerve swelling via nerve ultrasound (e.g. cross sectional area, CSA). EXPLORATORY OBJECTIVES: I. To obtain preliminary evidence on phenotypic differences between African-American and non African-American (A-A) (i.e., white, Asian, etc.) with regard to presentation of CIPN as well as response to the intervention. II. To obtain preliminary evidence of the effect of acupuncture on intraepidermal nerve fiber density (IENF) via skin biopsy. III. To examine the associations among the peripheral nerve assessment measures (nerve conduction, peripheral nerve ultrasound, skin biopsy) and of the peripheral nerve assessment measures with the patient reported outcomes (EORTC QLQ-CIN20, PRO-CTCAE) at baseline, week 12, and for the change from baseline to week 12. IV. To examine the association between expectations of the effectiveness of acupuncture to reduce peripheral neuropathy and baseline, 12 week, and change in patient-reported outcomes on the EORTC QLQ-CIPN20 and PRO-CTCAE. OUTLINE: Participants are randomized to 1 of 2 groups. GROUP 1: Participants undergo 8 45-minute acupuncture treatments over 10 weeks. GROUP 2: Participants receive usual care. After completion of study treatment, participants are followed up at 12 weeks.

Official Title
-----------------
Acupuncture for Chemotherapy-Induced Peripheral Neuropathy Among Breast Cancer Patients

Conditions
-----------------
Prognostic Stage II Breast Cancer AJCC v8, Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Grade 1 Peripheral Motor Neuropathy, CTCAE, Grade 1 Peripheral Sensory Neuropathy, CTCAE, Grade 2 Peripheral Motor Neuropathy, CTCAE, Grade 2 Peripheral Sensory Neuropathy, CTCAE, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8

Intervention / Treatment
-----------------
* Procedure: Acupuncture Therapy
* Other: Best Practice
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Breast and GI cancer stage I-III Currently receiving or recently completed neurotoxic chemotherapy (either adjuvant or neoadjuvant). Currently is defined as including up until when the next cycle would be delivered, that is if the patient is getting chemotherapy every week, this would include a week after their last treatment; if the patient is getting treatment every 2 weeks, this would include 2 weeks after their last treatment; if the patient is getting treatment every 3 weeks, this would include 3 weeks after their last treatment, etc. Recently completed is defined as 6 weeks after this time period. For example, if a patient was getting chemotherapy every week, this would include seven weeks after their last treatment; if the patient was getting treatment every 2 weeks, this would include 8 weeks after their last treatment; if the patient were getting treatment every 3 weeks, this would include 9 weeks after their last treatment, etc. Clinical symptoms of peripheral neuropathy of grade 1 or grade 2 as measured by the National Cancer Institute (NCI)-CTCAE Ability and willingness to understand and sign an informed consent Exclusion Criteria: Self-reported or documented history of UNRESOLVED pre-existing peripheral neuropathy due to diabetes, human immunodeficiency virus (HIV), or other conditions. Unable to provide medical history. Male patients. Pregnant. Unwilling to receive acupuncture or unable to travel for treatments.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (acupuncture)<br>Participants undergo 8 45-minute acupuncture treatments over 10 weeks. | Procedure: Acupuncture Therapy<br>* Undergo acupuncture therapy<br>* Other names: Acupuncture;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Group 2 (usual care)<br>Participants receive usual care. | Other: Best Practice<br>* Receive usual care<br>* Other names: standard therapy;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Sensory Neuropathic Pain Score as Measured by the European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Chemotherapy-Induced Peripheral Neuropathy (CIPN) 20 Item (20) | Will estimate means and standard deviations by group for the EORTC QLQ-CIPN20 sensory subscale, the correlation between the two measures, and the within-person change. To estimate effect size, we will use an analysis of covariance (ANCOVA) model at week 12, which will include the group and the baseline value. Using a 4-point Likert scale (1 = not at all, 2 = a little, 3 = quite a bit, and 4 = very much), individuals indicate the degree to which they have experienced sensory, motor, and autonomic symptoms during the past week. Sensory raw scale scores range from 1 to 36, motor raw scale scores range from 1 to 32, and autonomic raw scale scores range from 1 to 12 for men and 1-8 for women (erectile function item is excluded) [13]. All scale scores are linearly converted to a 0-100 scale, with higher scores indicating more symptom burden. | Baseline up to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Motor and Autonomic Pain Subscores on the EORTC QLQ-CIPN20 | Means and standard deviations will be computed at baseline and week 12 by group, and for the change in the measures, and will also estimate the correlation between the measures at the two time points, and fit ANCOVA models for each outcome. Using a 4-point Likert scale (1 = not at all, 2 = a little, 3 = quite a bit, and 4 = very much), individuals indicate the degree to which they have experienced sensory, motor, and autonomic symptoms during the past week. Sensory raw scale scores range from 1 to 36, motor raw scale scores range from 1 to 32, and autonomic raw scale scores range from 1 to 12 for men and 1-8 for women (erectile function item is excluded). All scale scores are linearly converted to a 0-100 scale, with higher scores indicating more symptom burden. | Baseline up to week 12 | 
| Change in Patient-Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) Measure of Numbness and Tingling | Means and standard deviations will be computed at baseline and week 12 by group, and for the change in the measures, and will also estimate the correlation between the measures at the two time points, and fit ANCOVA models for each outcome. The CTCAE measure of CIPN will be assessed using frequencies of grade by time point (baseline, week 12), as well as whether the grade of CIPN increased, decreased or remained stable. A Fisher's Exact test will be used to compare the groups at each time point and for the change during the study period. | Baseline up to week 12 | 
| CIPN as Measured by National Cancer Institute (NCI)-CTCAE 5.0 Grades 1-3 Numbness or Tingling | The CTCAE measure of CIPN will be assessed using frequencies of grade by time point (baseline, week 12), as well as whether the grade of CIPN increased, decreased or remained stable. A Fisher's Exact test will be used to compare the groups at each time point and for the change during the study period. | Up to week 12 | 
| Number of Participants With Standard Chemotherapy Dose or Decreased Due to Peripheral Neuropathy | Means and standard deviations will be computed at baseline and week 12 by group, and will also estimate the correlation between the measures at the two time points | Up to week 12 | 
| Number of Cycles of Completed Chemotherapy | Means and standard deviations will be computed at baseline and week 12 by group, and will also estimate the correlation between the measures at the two time points, and fit ANCOVA models for each outcome. | Up to week 12 | 
| Cross Sectional Area (CSA) of Peripheral Nerves as Determined by Ultrasound (Sural and Median) | Means and standard deviations will be computed at baseline and week 12 by group, and will also estimate the correlation between the measures at the two time points, and fit ANCOVA models for each outcome. | Up to week 12 | 
| Amplitude of Nerve Response Derived From Nerve Conduction Studies (NCS) (Sural, Tibial, and Median) | Means and standard deviations will be computed at baseline and week 12 by group, and will also estimate the correlation between the measures at the two time points, and fit ANCOVA models for each outcome. Nerve conduction studies measure impairment of electrical function in large peripheral nerves and measures amplitude and latency of neuronal signaling. Ranging from 0.1 μm to 20 μm. Reduction in the amplitude indicates axonal damage. | Up to week 12 | 
| Distal Latency of Nerve Response Derived From NCS (Sural, Tibial, and Median) | Means and standard deviations will be computed at baseline and week 12 by group, and will also estimate the correlation between the measures at the two time points, and fit ANCOVA models for each outcome. | Up to week 12 | 
| Conduction Velocity of Nerve Response Derived From NCS (Sural, Tibial, and Median) | Means and standard deviations will be computed at baseline and week 12 by group, and will also estimate the correlation between the measures at the two time points, and fit ANCOVA models for each outcome. | Up to week 12 | 
| Nerve Fiber Density in the Skin | Means and standard deviations will be computed at baseline and week 12 by group, and will also estimate the correlation between the measures at the two time points, and fit ANCOVA models for each outcome. | Up to week 12 |