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

Phase 2

Completed

• Conditions: Gastric Carcinoma; Appendix Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Pancreatic Neuroendocrine Tumor; Pancreatic Carcinoma; Esophageal Carcinoma; Rectal Carcinoma; Small Intestinal Carcinoma; Anal Carcinoma; Colon Carcinoma
• Interventions: Procedure: Acupuncture Therapy; Procedure: Oral Cryotherapy; Procedure: Acupressure Therapy; Other: Questionnaire Administration; Other: Quality-of-Life Assessment

• Registration Number: NCT04505553
• Lead Sponsor: University of Washington

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-07-31
• Study First Submitted QC: 2020-08-05
• Study First Posted: 2020-08-10
• Study Start: 2021-06-01
• Primary Completion: 2024-03-07
• Study Completion: 2024-03-31
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-24
• Last Update Posted: 2024-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 77

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (acupuncture, acupressure, cryotherapy)	Quality-of-Life Assessment	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 I (acupuncture, acupressure, cryotherapy)	Acupuncture Therapy	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 I (acupuncture, acupressure, cryotherapy)	Questionnaire Administration	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 (cryotherapy)	Oral Cryotherapy	Patients undergo standard of care oral cryotherapy.
Arm II (cryotherapy)	Questionnaire Administration	Patients undergo standard of care oral cryotherapy.
Arm I (acupuncture, acupressure, cryotherapy)	Oral Cryotherapy	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 I (acupuncture, acupressure, cryotherapy)	Acupressure Therapy	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 (cryotherapy)	Quality-of-Life Assessment	Patients undergo standard of care oral cryotherapy.

Primary Outcome Measures

Name	Time	Method
Severity of chemotherapy-induced peripheral neuropathy (CIPN)	At 3 months	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.

Secondary Outcome Measures

Name	Time	Method
Severity of CIPN: Neuropen assessment of patients' perceived pain and pressure	3 months	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.
Incidence of grade 2 or higher CIPN	3 months	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.
Proportion of patients assigned to the intervention arm who complete 60% of acupuncture treatments	3 months	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.
Severity of CIPN: Tuning fork vibration sensation testing	3 months	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.
Incidence of pain, fatigue, nausea, and anxiety	3 months	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.

Trial Locations

Locations (1)

Fred Hutch/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States