Acupuncture and Exercise for EV-Pembro-Induced Peripheral Neuropathy (ACE)

Acupuncture and Exercise for EV-Pembro-Induced Peripheral Neuropathy (ACE)

The goal of this study is to evaluate the feasibility and preliminary efficacy of a combined acupuncture and exercise intervention for the management of chemotherapy-induced peripheral neuropathy (CIPN) in participants with metastatic bladder cancer receiving enfortumab vedotin (EV) and pembrolizumab (Pembro).

The names of the two study groups in this research study are:

• Acupuncture + Virtual Exercise (AVE)
• Virtual Exercise Only (VE)

Study Overview

• Status: Not yet recruiting
• Conditions: Peripheral Neuropathy; Metastatic Urothelial Cancer; Advanced Urothelial Cancer; Metastatic Bladder Cancer
• Intervention / Treatment: Procedure: Acupuncture; Behavioral: Exercise

Detailed Description

The goal of this study is to evaluate the feasibility and preliminary efficacy of a combined acupuncture and exercise intervention for the management of chemotherapy-induced peripheral neuropathy (CIPN) in participants with metastatic bladder cancer receiving enfortumab vedotin (EV) and pembrolizumab (Pembro).

CIPN is a side effect of some kinds of chemotherapy, and can lead to pain, numbness, tingling, swelling, or muscle weakness, primarily in the hands and feet and may persist for months or even years after chemotherapy ends.

Acupuncture involves using tiny needles to stimulate nerves and pathways in the body, and early research shows it might be helpful in reducing symptoms of CIPN.

Participants will be randomized in a 1:1 fashion into one of two study groups: AVE Arm: Acupuncture + Virtual Exercise or VE Arm: Virtual Exercise Only. Randomization means a participant is placed into a study group by chance.

The research study procedures include screening for eligibility, questionnaires, sensory tests, cycling test, and physical performance tests.

Participation in this research study is expected to last about 12 weeks.

About 50 people will take part in this study.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christina Dieli-Conwright, PhD, MPH; Phone Number: 617-582-8321; Email: ChristinaM_Dieli-Conwright@dfci.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
      • Principal Investigator: Christina Dieli-Conwright, PhD
      • Contact: Christina Dieli-Conwright, PhD, MPH; Phone Number: 617-632-3800; Email: ChristinaM_Dieli-Conwright@dfci.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years old
• Diagnosed with pathologically proven advanced or metastatic urothelial cancer (mUC)
• Planning to receive treatment with EV-Pembro or have received up to two cycles of EV-Pembro treatment with enrollment occurring prior to the start of the third cycle
• Self-reported ability to walk for 6 minutes and/or 2 blocks
• Deemed acceptable for exercise by their treating provider
• Sedentary, currently engaging in less than or equal to 60 minutes of moderate or vigorous structured exercise/week, as assessed by the Godin Leisure-Time Exercise Questionnaire
• Willing to adhere to all study-related procedures, including randomization to one of the two possible acupuncture treatments
• Eligible per verbally administered Physical Activity Readiness Questionnaire (PAR-Q+)
• Referrals to physical therapy are allowed during the study if necessary; and
• Participants taking any of medications listed below must be on a stable regimen, with no changes in the past three months. Use of these medications may continue while on study.
• Duloxetine, amitriptyline, nortriptyline, gabapentin, and pregabalin

Exclusion Criteria:

• History of peripheral neuropathy prior to EV-Pembro initiation
• Patients with a pacemaker or other electronically charged medical device; or
• Participate in more than 60 minutes of moderate or vigorous structured exercise/week

Investigators will not include the following special populations:

• Adults unable to consent
• Individuals who are not yet adults (infants, children, teenagers < 18 years)
• Pregnant women
• Prisoners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm AVE: Acupuncture + Virtual Exercise; 25 participants will complete: In-clinic baseline visit; 3 exercise sessions with certified trainer per week; 1 in-clinic acupuncture session per week; One or two end of study in-clinic visits	Procedure: Acupuncture; Acupuncture treatment with licensed acupuncturist.; Behavioral: Exercise; Virtually supervised, technology-based aerobic and resistance exercise program. Exercise bike and resistance bands will be provided to participants. Exercise sessions will be via HIPAA-compliant, teleconference platform Zoom.
Active Comparator: Arm VE: Virtual Exercise; 25 participants will complete: In-clinic baseline visit; 3 exercise sessions with certified trainer per week; One or two end of study in-clinic visits	Behavioral: Exercise; Virtually supervised, technology-based aerobic and resistance exercise program. Exercise bike and resistance bands will be provided to participants. Exercise sessions will be via HIPAA-compliant, teleconference platform Zoom.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropathic Pain Scale (NPS) Score Change from Baseline	NPS is a multidimensional tool that uses a self-report numerical rating scale (0-10) to quantify global pain intensity, unpleasantness, and eight additional descriptive qualities of neuropathic pain, Scores on each 0-10 scale are patient-reported, with higher scores indicating greater pain intensity or unpleasantness. In addition, the NPS includes one semi-structured question that assesses the temporal sequence of pain.	At 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brief Pain Inventory-Short Form (BPI-SF) Score Change from Baseline	BPI-SF is a validated self-report questionnaire that assesses pain severity and pain-related interference with daily functioning. Each item is rated on a 0-10 scale, with higher scores indicating greater pain severity or interference.	Participants will complete BPI-SF survey at baseline, week 3, 6, 9 and 12.
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-Ntx) Score Change from Baseline	The FACT/GOG-Ntx is a patient-reported questionnaire developed to assess chemotherapy-induced peripheral neuropathy (CIPN). It includes an 11-item neurotoxicity (Ntx) subscale that evaluates sensory, motor, and hearing neuropathy, as well as functional impairments associated with neuropathy. Scores are rated on a Likert-type scale, with higher scores indicating better functioning and fewer/less severe neuropathy symptoms.	The FACT/GOG-Ntx will be completed at baseline, and weeks 3, 6, 9, and 12.
Chemotherapy-Induced Peripheral Neuropathy-20 (CIPN-20) Score Change from Baseline	CIPN-20 is a patient-reported quality of life questionnaire consisting of 20 items that assess sensory, motor, and autonomic symptoms associated with chemotherapy-induced peripheral neuropathy. Items are rated on a 4-point Likert scale, and all scale scores are linearly converted to a 0-100 scale, with higher scores indicating greater symptom burden	CIPN-20 will be completed as baseline, week 6 and 12.
Quantitative Sensory Testing (QST) Scores Change from Baseline	Quantitative sensory testing (QST) objectively evaluates sensory nerve function and pain processing across several measurable modalities. Tactile detection is tested with Von Frey filaments (0.008-300 g), vibration with a biothesiometer (0-50 V), and thermal detection/pain thresholds with a TSA-II device (0-50°C) for warm, cool, heat-pain, and cold-pain responses. Mechanical pain threshold is measured using pinprick stimulators (8-512 mN). Conditioned pain modulation is calculated from the change in 0-100 pain ratings for heat stimuli given before versus during cold-water exposure. Pressure pain threshold is assessed at the thumbnail using controlled pressure from 0.25 to 10 kgf/cm². Higher values generally indicate less pain sensitivity or higher detection thresholds; lower values suggest greater pain sensitivity or sensory impairment.	QST will be completed at baseline and week 12 (PPT and CPM will be assessed at baseline only).
Relative Dose Intensity (RDI)	The planned total dose (PTD) of EV-Pembro therapy is defined as the total dose scheduled to be administered divided by the planned duration of therapy. The actual total dose (ATD) represents the average dose administered over the participant's actual treatment period. Relative dose intensity (RDI) is expressed as the actual dose intensity as a percentage of the planned dose intensity (ATD relative to PTD)	RDI calculated at 12 weeks.
Treatment Delays Rate (TDR)	TDR is defined as the proportion of participants who experienced one or more deviations from the planned dosing schedule for EV-Pembro during the treatment period.	Up to 12 weeks
Treatment Related Adverse Event (AE) Rate	Treatment related AE rate is defined as the proportion of participants experienced at least one treatment related AE. Events assessed as possibly, probably, or definitely related will be counted as treatment-related. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).	Up to 12 weeks
Early Discontinuation Rates (EDR)	EDR is defined as the proportion of participants who stopped EV or Pembrolizumab before completing the planned 12-week treatment for any reason.	At 12 weeks
Weekly Exercise Session Completion Rates	The weekly exercise session completion rate is defined as the proportion of prescribed exercise sessions completed by each participant during the 12-week intervention	Assessed weekly during the 12-week intervention.
Program Retention Rate	Program retention rate is defined as the proportion of participants who remain enrolled and actively participating in the exercise program.	Assessed at 3, 6, and 12 weeks

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Christina Dieli-Conwright, PhD, MPH, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): October 2, 2026
• Primary Completion (Estimated): March 2, 2027
• Study Completion (Estimated): March 2, 2027

Study Registration Dates

• First Submitted: April 17, 2026
• First Submitted That Met QC Criteria: April 17, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: mUC; Enfortumab Vedotin-Induced Neuropathy; Pembrolizumab-Induced Neuropathy
• Additional Relevant MeSH Terms: Urogenital Diseases; Nervous System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neuromuscular Diseases; Urologic Neoplasms; Urinary Bladder Diseases; Peripheral Nervous System Diseases; Urinary Bladder Neoplasms; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Complementary Therapies; Exercise; Acupuncture Therapy
• Other Study ID Numbers: 25-454

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Harvard Cancer Consortium encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer office for Dana -Farber Innovations (BODFI) at innovations@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes