Advanced Urothelial Cancer, Bladder Cancer, Metastatic Bladder Cancer, Metastatic Urothelial Cancer, Peripheral Neuropathy, Urothelial Cancer
Conditions
Keywords
Enfortumab Vedotin-Induced Neuropathy, Pembrolizumab-Induced Neuropathy, mUC, UC
Brief summary
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 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)
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 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 20 people will take part in this study.
Interventions
PROCEDUREAcupuncture
Acupuncture treatment with licensed acupuncturist.
BEHAVIORALExercise
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.
Sponsors
Dana-Farber Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years old * Diagnosed with pathologically proven urothelial cancer (UC) * Have received at least one cycle of EV-Pembro treatment with enrollment occurring after the 1st cycle and prior to the 4th 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 either treatment group * Referrals to physical therapy are allowed during the study if necessary * 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 * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety of efficacy assessment of investigational regimen will be eligible.
Exclusion criteria
* History of documented grade 2 or greater peripheral or motor neuropathy prior to EV-Pembro initiation; may confound assessment of the intervention's preventative effect * Patients with uncontrolled medical conditions that would preclude them from participating in moderate-to-vigorous intensity exercise in a virtual setting. Given the exercise environment is virtual, only patients with stable medical conditions should be enrolled to ensure their safety. Physical Activity Readiness Questionnaire (PARQ+) will be used during screening to facilitate conversations about present or historical medical conditions * Having continued grade 2 or higher adverse effects of their current treatment (EV-Pembro) * Receiving more than 10mg prednisone daily for any condition * History of bleeding diathesis (von Willebrand disease, hemophilia A/B) * Known history of seizure disorder or taking antiepileptic drugs * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neuropathic Pain Scale (NPS) Score Change from Baseline | At 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brief Pain Inventory-Short Form (BPI-SF) Score Change from Baseline | Participants will complete BPI-SF survey at baseline, week 3, 6, 9 and 12. | 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. |
| Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-Ntx) Score Change from Baseline | The FACT/GOG-Ntx will be completed at baseline, and weeks 3, 6, 9, and 12. | 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. |
| Chemotherapy-Induced Peripheral Neuropathy-20 (CIPN-20) Score Change from Baseline | CIPN-20 will be completed as baseline, week 6 and 12. | 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 |
| Quantitative Sensory Testing (QST) Scores Change from Baseline | QST will be completed at baseline and week 12 (PPT and CPM will be assessed at baseline only). | 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. |
| Relative Dose Intensity (RDI) | RDI calculated at 12 weeks. | 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) |
| Treatment Delays Rate (TDR) | Up to 12 weeks | 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. |
| Treatment Related Adverse Event (AE) Rate | Up to 12 weeks | 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). |
| Early Discontinuation Rates (EDR) | At 12 weeks | EDR is defined as the proportion of participants who stopped EV or Pembrolizumab before completing the planned 12-week treatment for any reason. |
| Weekly Exercise Session Completion Rates | Assessed weekly during the 12-week intervention. | The weekly exercise session completion rate is defined as the proportion of prescribed exercise sessions completed by each participant during the 12-week intervention |
| Program Retention Rate | Assessed at 3, 6, and 12 weeks | Program retention rate is defined as the proportion of participants who remain enrolled and actively participating in the exercise program. |
Countries
United States
Contacts
CONTACTChristina Dieli-Conwright, PhD, MPH
PRINCIPAL_INVESTIGATORChristina Dieli-Conwright, PhD, MPH
Dana-Farber Cancer Institute
Outcome results
None listed