Oral Cryotherapy Plus Acupressure and Acupuncture Versus Oral Cryotherapy for Decreasing Chemotherapy-Induced Peripheral Neuropathy From Oxaliplatin-Based Chemotherapy in Patients With Gastrointestinal Cancer

Study Overview
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Brief Summary
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This phase II trial investigates how well oral cryotherapy plus acupressure and acupuncture compared with oral cryotherapy alone work in decreasing chemotherapy-induced peripheral neuropathy in patients with gastrointestinal cancer who are receiving oxaliplatin-based chemotherapy. Acupressure is the application of pressure or localized massage to specific sites on the body to control symptoms such as pain or nausea. Acupuncture is the technique of inserting thin needles through the skin at specific points on the body to control pain and other symptoms. Cryotherapy uses cold temperature such as oral ice chips to prevent abnormally increased pain sensation. Giving oral cryotherapy with acupressure and acupuncture may work better in decreasing chemotherapy-induced peripheral neuropathy from oxaliplatin-based chemotherapy in patients with gastrointestinal cancer compared to oral cryotherapy alone.

Detailed Description
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OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo acupuncture during chemotherapy infusion on day 1 and fluorouracil pump disconnect on day 3 of each biweekly chemotherapy infusion over 12 weeks. Patients also undergo self-administered acupressure over 11 minutes daily for 12 weeks and undergo standard of care oral cryotherapy. ARM II: Patients undergo standard of care oral cryotherapy.

Official Title
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Pilot Study of Oral Cryotherapy vs. Oral Cryotherapy Plus Acupuncture and Acupressure to Decrease Chemotherapy-Induced Peripheral Neuropathy From Oxaliplatin-Based Chemotherapy for GI Cancers

Conditions
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Appendix Carcinoma, Colon Carcinoma, Esophageal Carcinoma, Gastric Carcinoma, Liver and Intrahepatic Bile Duct Carcinoma, Malignant Digestive System Neoplasm, Pancreatic Carcinoma, Rectal Carcinoma, Small Intestinal Carcinoma, Anal Carcinoma, Digestive System Carcinoma, Digestive System Neuroendocrine Tumor, Pancreatic Neuroendocrine Tumor

Intervention / Treatment
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* Procedure: Acupuncture Therapy
* Procedure: Acupressure Therapy
* Procedure: Oral Cryotherapy
* Other: Questionnaire Administration
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: GI cancer (primary esophagus, gastric, pancreas, biliary, liver, small bowel, appendix, colon, rectal, anal, or gastrointestinal/pancreatic neuroendocrine tumor) scheduled to receive a new start of fluorouracil (5-FU), oxaliplatin, +/- irinotecan (fluorouracil/leucovorin calcium/oxaliplatin [FOLFOX], fluorouracil/irinotecan/leucovorin calcium/oxaliplatin [FOLFIRINOX], leucovorin/fluorouracil/oxaliplatin/irinotecan [FOLFOXIRI] regimens) with plan for >= 3 months of therapy with the regimen. Chemotherapy can be given for neoadjuvant, adjuvant, or palliative intent. 1 dose (cycle) of the intended regimen is permitted prior to study enrollment. **There is no limitation on the addition of a biologic agent to one of the above chemotherapy regimens, including, but not limited to: bevacizumab, cetuximab, panitumumab, trastuzumab, or the biosimilars of these agents Age >=18 years Absolute neutrophil count > 0.5 thousand/microL Platelet count > 20 thousand/microL Not currently pregnant Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Baseline peripheral neuropathy from any cause Planned oxaliplatin with capecitabine Planned initial dose of oxaliplatin < 100% of the standard regimen-specified dose. For most regimens, this would be 85 mg/m^2 intravenously (IV) dosed every 14 days Receipt of acupuncture treatment in the prior 3 months Use of concomitant duloxetine for minimization of neuropathy Psychiatric illness/social situations that would limit compliance with study requirements

Ages Eligible for Study
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Minimum Age: 18 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 I (acupuncture, acupressure, cryotherapy)<br>Patients undergo acupuncture during chemotherapy infusion on day 1 and fluorouracil pump disconnect on day 3 of each biweekly chemotherapy infusion over 12 weeks. Patients also undergo self-administered acupressure over 11 minutes daily for 12 weeks and undergo standard of care oral cryotherapy. | Procedure: Acupuncture Therapy<br>* Undergo acupuncture<br>* Other names: Acupuncture;Procedure: Acupressure Therapy<br>* Undergo acupressure<br>* Other names: Ischemic Compression;Procedure: Oral Cryotherapy<br>* Undergo oral cryotherapy<br>Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|
| Active Comparator: Arm II (cryotherapy)<br>Patients undergo standard of care oral cryotherapy. | Procedure: Oral Cryotherapy<br>* Undergo oral cryotherapy<br>Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of chemotherapy-induced peripheral neuropathy (CIPN) | Measured by the European Organization for Research and Treatment of Cancer (EORTC)-CIPN 20. Severity of CIPN will be summarized for each treatment arm, and treatment comparisons made via linear regression model with adjustment for baseline severity level. The EORTC QLQ-CIPN20 is a 20-item questionnaire that evaluates CIPN using 3 subscales that assess sensory (9 items), motor (8 items), and autonomic (3 items) symptoms and functioning with each item measured on a 1-4 scale (1, not at all; 4, very much). The sensory subscale raw scores range from 1 to 36. The CIPN-20 subscale raw scores are linearly converted to a 0-100 scale such that a high score corresponds to a worse condition or more symptoms. | At 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of grade 2 or higher CIPN | Measured by Common Terminology Criteria for Adverse Events (CTCAE) version 5. Incidences of CIPN (grade 2 or higher), pain, fatigue, nausea, and anxiety will be compared between treatment arms using Chi-squared or Fisher's exact tests as appropriate. | 3 months | 
| Severity of CIPN: Neuropen assessment of patients' perceived pain and pressure | The Neuropen is used to assess touch and pressure perception as well as protective pain and sharpness sensation. Touch and pressure sensation will be assessed using a 10-g monofilament on the subject's dominant foot. Pain and subjective sharpness sensation will be assessed using the 40-g Neurotip on the dominant foot. Loss of pain and pressure sensation are associated with increased CIPN. | 3 months | 
| Severity of CIPN: Tuning fork vibration sensation testing | A study-specific 128-Hz tuning fork will be used to assess vibration sensation on dominant lower extremity and dominant upper extremity sites. If the patient feels the vibration for 15 seconds or longer, this is defined as normal. If the patient feels the vibration less than 15 seconds, this is defined as absent or decreased vibration sensation. Vibration sensation is lost sooner in CIPN, which means that shorter duration of vibration scores are associated with increased CIPN. | 3 months | 
| Proportion of patients assigned to the intervention arm who complete 60% of acupuncture treatments | Adherence to acupuncture treatment among patients in the intervention arm will be described as a proportion with 95% confidence interval. Reasons for treatment non-adherence and delivered dose intensity of chemotherapy will be noted. | 3 months | 
| Incidence of pain, fatigue, nausea, and anxiety | Measured by patient-reported (National Cancer Institute [NCI] Patient Reported Outcomes [PRO]-CTCAE, Brief Pain Inventory [BPI], oral dysesthesia) and provider-assessed (CTCAE version 5) grading scales. | 3 months |