Biomarkers in Chemotherapy-Induced Peripheral Neurotoxicity (CIPN)

Biomarkers in Chemotherapy-Induced Peripheral Neurotoxicity: Better Tools and Understanding

This pilot study will attempt to establish the feasibility of using tissue oxygen measurements and the protein, neurofilament light chain (NF-L), as potential biomarkers for chemotherapy-induced peripheral neuropathy (CIPN). Thirty (30) subjects scheduled to begin taxane-based chemotherapy for breast tumor will be assigned to receive an India ink injection under the skin of the foot. The ink will be used to make up to five (5) 45-minute "electron paramagnetic resonance" (EPR) oximetry readings prior to the start of chemotherapy. Subjects will undergo electrophysiologic assessments including nerve conduction studies, in addition to a neurological examination prior to the start of chemotherapy. Subjects will have the EPR oximetry readings, electrophysiologic tests, and neurological examination two more times: at the halfway point of their chemotherapy treatment -- or at the onset of CIPN symptoms -- and again after chemotherapy has been completed. Subjects will also have blood drawn prior to beginning taxane-based chemotherapy, prior to every scheduled chemotherapy treatment, and after completion of chemotherapy in order to test for neurofilament light chain (NF-L).

Study Overview

• Status: Completed
• Conditions: CIPN - Chemotherapy-Induced Peripheral Neuropathy
• Intervention / Treatment: Diagnostic test: EPR Oximetry

Detailed Description

Therapy with chemotherapeutic drugs can make a huge impact on survival and quality of life in patients with cancer. Advances in medical monitoring and the effectiveness of these therapies have significantly improved outcomes so that a definitive cure or long-term survival is more likely. Cancer survivors are used to dealing with serious side effects of their therapy; however, some of the side effects from the chemotherapy drugs persist even after the medication course is completed. The impact of these sequelae on quality of survival is increasingly being appreciated and forming an important new direction of cancer care. One of the more severe side effects of chemotherapy is peripheral neurotoxicity resulting in neuropathy or neuronopathy.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the least predictable and most prolonged sequelae with effects ranging from pain, numbness and tingling to diffuse weakness sometimes to the extent of paralysis. It results from damage or alteration in function of peripheral nerves usually, but not always, in a length-dependent manner. An indirect impact of CIPN includes difficulties with balance and susceptibility to falls. There are currently no therapies that have been proven to prevent CIPN. Similarly, there are few medications that are known to be effective in the reversing CIPN once it develops or effectively treating symptoms of CIPN. Currently, diagnosis is based mainly on clinical examination and electrophysiological testing to monitor CIPN; identification of candidate biomarkers through which disease onset can be identified at an earlier stage and which reflect presumed pathophysiologic mechanisms is of paramount importance.

There are different theories of CIPN pathogenesis. One of the leading hypotheses relates to mitochondrial dysfunction and oxidative stress affecting both the dorsal root ganglia neurons and supportive endothelial cells of the vasa nervorum. Here at Dartmouth, a specialized technique has been developed that allows the non-invasive assessment of tissue oxygen in and around peripheral nerve. This technique, called "electron paramagnetic resonance" (EPR) oximetry, allows for repeated measurements over time that can be correlated with other metrics of peripheral nerve function. Given its relevance to an important pathophysiologic mechanism of disease, EPR oximetry may provide an early marker of disease onset.

Neurofilament light chain (NF-L) is also emerging as a sensitive blood-based biomarker of axonal degeneration. NF-L is a component of the axonal cytoskeleton that leaks out of degenerating axons. NF-L has been reported to be elevated in plasma or serum in a wide range of neurodegenerative disorders, including CNS disorders such as multiple sclerosis and ALS as well as PNS disorders such as Charcot Marie Tooth and Guillain-Barre syndrome. To date, there are no published reports of elevated blood NF-L levels in patients with CIPN, although it has been reported to increase in rat model of vincristine-induced neuropathy.

In this proposal, the investigators will be testing the hypothesis that these could both be biomarkers of CIPN. It is hoped that the oximetry measurement and blood NF-L levels will (i) reflect the changes that occur on a cellular level and the damaged nerves, (ii) reflect the damage occurring to nerves more sensitively than existing techniques, and (iii) help to better understand the reason the nerves are being damaged. It is also hoped that these will be something that can be used in future clinical trials.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth-Hitchcock Medical Center in Lebanon, NH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Scheduled to receive chemotherapy with taxane compounds for the treatment of breast cancer.
• No prior taxane or platinum chemotherapy prior to enrollment.
• Life expectancy greater than or equal to 12 months.
• Able to provide independent informed consent for the study.
• Able to undergo EPR oximetry
• Age 18 years or older

Exclusion Criteria:

• Central nervous system or other impairments that interfere with clinical and electrophysiological assessment.
• Unable to provide independent informed consent.
• Pacemaker or other metallic objects that would be contraindicated for MRI.
• A requirement for supplemental oxygen at baseline, or known, severe chronic obstructive pulmonary disease .
• Previous exposure to neurotoxic chemotherapeutic agents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: EPR Oximetry; All subjects in the study will receive the paramagnetic India ink injection to the foot. At three time points (pre-exposure, during-exposure or CIPN incidence, and post exposure), subjects will have three EPR oximetry readings, a neurological examination, and electrophysiologic testing.

Diagnostic test: EPR Oximetry; Subjects will have up to five EPR oximetry readings at each study visit. Subjects will place the foot with the paramagnetic ink injection between the two magnets of the EPR device. Continuous scans will be acquired for 10 minutes while the subject breathes room air, 10 minutes while the subject breathes enriched 100% oxygen, and 10 minutes while breathing room air again.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative Change in % pO2	EPR Oximetry will measure tissue oxygen levels in the injected foot during 10 minutes of breathing room air, 10 minutes while breathing 100% oxygen, and 10 minutes of room air.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurologic Examination_ Strength_ Toe Fan	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. MRC scale for muscle strength (0-5) Grade 5: Normal Grade 4: Movement against gravity and resistance Grade 3: Movement against gravity over (almost) the full range Grade 2: Movement of the limb but not against gravity Grade 1: Visible contraction without movement of the limb (not existent for hip flexion) Grade 0: No visible contraction	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Strength_ Toe Flex	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. MRC scale for muscle strength (0-5) Grade 5: Normal Grade 4: Movement against gravity and resistance Grade 3: Movement against gravity over (almost) the full range Grade 2: Movement of the limb but not against gravity Grade 1: Visible contraction without movement of the limb (not existent for hip flexion) Grade 0: No visible contraction	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Strength_ Inv	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. MRC scale for muscle strength (0-5) Grade 5: Normal Grade 4: Movement against gravity and resistance Grade 3: Movement against gravity over (almost) the full range Grade 2: Movement of the limb but not against gravity Grade 1: Visible contraction without movement of the limb (not existent for hip flexion) Grade 0: No visible contraction	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Strength_ Ev	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. MRC scale for muscle strength (0-5) Grade 5: Normal Grade 4: Movement against gravity and resistance Grade 3: Movement against gravity over (almost) the full range Grade 2: Movement of the limb but not against gravity Grade 1: Visible contraction without movement of the limb (not existent for hip flexion) Grade 0: No visible contraction	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Strength_ ADF	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. MRC scale for muscle strength (0-5) Grade 5: Normal Grade 4: Movement against gravity and resistance Grade 3: Movement against gravity over (almost) the full range Grade 2: Movement of the limb but not against gravity Grade 1: Visible contraction without movement of the limb (not existent for hip flexion) Grade 0: No visible contraction	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Vibration Sense_Toe	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. The position of the intersect is recorded on an arbitrary scale from 0 to 8 on a Rydel-Seiffer tuning fork once the subject is no longer perceiving vibration. The higher the number, the better the vibratory sense.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Vibration Sense_MM	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. The position of the intersect is recorded on an arbitrary scale from 0 to 8 on a Rydel-Seiffer tuning fork once the subject is no longer perceiving vibration. The higher the number, the better the vibratory sense.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Vibration Sense_Knee	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. The position of the intersect is recorded on an arbitrary scale from 0 to 8 on a Rydel-Seiffer tuning fork once the subject is no longer perceiving vibration. The higher the number, the better the vibratory sense.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Vibration Sense_DIP2	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. The position of the intersect is recorded on an arbitrary scale from 0 to 8 on a Rydel-Seiffer tuning fork once the subject is no longer perceiving vibration. The higher the number, the better the vibratory sense.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Vibration Sense_DIP5	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. The position of the intersect is recorded on an arbitrary scale from 0 to 8 on a Rydel-Seiffer tuning fork once the subject is no longer perceiving vibration. The higher the number, the better the vibratory sense.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Deep Tendon Reflexes _ Biceps	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. REFLEX SCALE for Deep Tendon Reflexes (DTRs) The score ranges from 0 - 9, where 0 is no reflex response (areflexia)/always abnormal, greater than 1 and less than 3 is normal, and 9 is a tap that elicits a repeating reflex (clonus)/always abnormal.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Deep Tendon Reflexes _ Triceps	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. REFLEX SCALE for Deep Tendon Reflexes (DTRs) The score ranges from 0 - 9, where 0 is no reflex response (areflexia)/always abnormal, greater than 1 and less than 3 is normal, and 9 is a tap that elicits a repeating reflex (clonus)/always abnormal.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Deep Tendon Reflexes _ BR	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. REFLEX SCALE for Deep Tendon Reflexes (DTRs) The score ranges from 0 - 9, where 0 is no reflex response (areflexia)/always abnormal, greater than 1 and less than 3 is normal, and 9 is a tap that elicits a repeating reflex (clonus)/always abnormal.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Deep Tendon Reflexes _ Patella	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. REFLEX SCALE for Deep Tendon Reflexes (DTRs) The score ranges from 0 - 9, where 0 is no reflex response (areflexia)/always abnormal, greater than 1 and less than 3 is normal, and 9 is a tap that elicits a repeating reflex (clonus)/always abnormal.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Neurologic Examination_ Deep Tendon Reflexes _ Achilles	Patients will be phenotyped by a neurologic examination before and after exposure to a standard regimen of neurotoxic chemotherapy. REFLEX SCALE for Deep Tendon Reflexes (DTRs) The score ranges from 0 - 9, where 0 is no reflex response (areflexia)/always abnormal, greater than 1 and less than 3 is normal, and 9 is a tap that elicits a repeating reflex (clonus)/always abnormal.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Nerve Conduction Metrics (Amplitude)_DORSAL SURAL	Electrophysiologic testing will measure nerve conduction amplitude in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Change in Nerve Conduction Metrics (Amplitude)_MED PLANTAR	Electrophysiologic testing will measure nerve conduction amplitude in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Change in Nerve Conduction Metrics (Amplitude)_SURAL	Electrophysiologic testing will measure nerve conduction amplitude in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean of the Difference in Nerve Conduction Amplitudes Between Pre-Mid and Pre-Post exposure_Dorsal Sural	Electrophysiologic testing will measure nerve conduction amplitude in patients before and after exposure to a standard regimen of neurotoxic chemotherapy. The outcome measure is reporting the average of the differences in amplitudes Pre-Mid and Pre-Post exposure (for example, the change from Pre and Mid is calculated, and then the change across all participants is averaged).	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Change in Nerve Conduction/Mixed Nerve Amplitudes _Medial Plantar	Electrophysiologic testing will measure nerve conduction amplitude in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Change in Nerve Conduction/Mixed Nerve Amplitudes _Sural	Electrophysiologic testing will measure nerve conduction amplitude in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Change in Nerve Conduction_Motor_ (Amplitude)_Peron-EDB	Electrophysiologic testing will measure nerve conduction amplitude in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Change in Nerve Conduction_Motor_ (Amplitude)_Peron-TA	Electrophysiologic testing will measure nerve conduction amplitude in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Change in Nerve Conduction_Motor_ (Amplitude)_Tibial-AH	Electrophysiologic testing will measure nerve conduction amplitude in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Nerve Conduction Metrics as Measured by Mean Change (Velocity) for Peroneal CMAP AMP, EDB	Electrophysiologic testing will measure nerve conduction velocity in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Nerve Conduction Metrics as Measured by Mean Change (Velocity) for Peroneal CMAP, AT	Electrophysiologic testing will measure nerve conduction velocity in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Nerve Conduction Metrics as Measured by Mean Change (Velocity) for Tibial CMAP, AH	Electrophysiologic testing will measure nerve conduction velocity in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Nerve Conduction Metrics as Measured by Mean Change (Velocity) for Dorsal Sural CV	Electrophysiologic testing will measure nerve conduction velocity in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Nerve Conduction Metrics as Measured by Mean Change (Velocity) for Med Plantar CV	Electrophysiologic testing will measure nerve conduction velocity in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Nerve Conduction Metrics as Measured by Mean Change (Velocity) for Sural CV	Electrophysiologic testing will measure nerve conduction velocity in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Nerve Conduction Metrics as Measured by Mean Change (Velocity) for Peroneal CV, Distal	Electrophysiologic testing will measure nerve conduction velocity in patients before and after exposure to a standard regimen of neurotoxic chemotherapy.	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Score of Neuro-Quality of Life - Positive Affect and Well-Being Scale	Neuropathy-Specific Quality of Life scale measuring Positive Affect and Well Being The range in score is 23 to 115, with a low score indicating a less positive affect and well-being	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Score of Neuro-Quality of Life - Satisfaction With Social Roles and Activities Scale	Neuropathy-Specific Quality of Life scale measuring Satisfaction with Social Roles and Activities The range in scores is 47 to 235, with a lower score indicating less satisfaction with social roles and activities	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Score of Neuro-Quality of Life - Lower Extremity Function (Mobility) Scale	Neuropathy-Specific Quality of Life scale measuring Lower Extremity Function (Mobility) The range in scores is 19 to 95, with a lower score indicating more difficulty with lower extremity function	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Score of Neuro-Quality of Life - Upper Extremity Function (Fine Motor, Activities of Daily Living) Scale	Neuropathy-Specific Quality of Life scale measuring Upper Extremity Function (Fine Motor, Activities of Daily Living) The range in scores is 20 to 100, with a low score indicating more difficulty with upper extremity function	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Score of The Neuropathy Total Symptom Score-6 Questionnaire	Neuropathy Total Symptom Score questionnaire with 6 questions The range is scores is 0 to 22 with a higher score indicating worse symptoms	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Score of Toronto Clinical Neuropathy Scoring System	Toronto Clinical Neuropathy Scoring System The range in scores is 0 to 19 with higher scores indicating worse neuropathy	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Score of National Cancer Institute - Common Toxicity Criteria	National Cancer Insitute - Common Toxicity Criteria The range in scores is 0 to 5, with higher scores indicating worse toxicity	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Score of Total Neuropathy Scores	Total Neuropathy score The range in scores is 0 to 40, with higher scores indicating worse neuropathy	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Score of Survey of Autonomic Symptoms, Column B	Survey of Autonomic Symptoms, questions in Column B The range in scores is 0 to 55 for women and 0 to 60 for men, with higher scores indicating more bothersome symptoms	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Score of McGill Pain Visual Analog Scale	McGill Visual Analog Scale for Pain The range in scores is 0 to 100, with 0 indicting "No pain" and 100 indicating "Worst pain possible"	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Scores of Short Form McGill Pain Questionnaire	Short Form McGill Pain Questionnaire The range in scores is 0 to 15, with higher scores indicating worse pain	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Mean Score of Survey of Autonomic Symptoms, Column A	Survey of Autonomic Symptoms, questions in column A The range in scores is 0 to 11 for women and 0 to 12 for men, with higher scores indicating more symptoms	Pre-chemotherapy (Baseline), Mid-chemotherapy (approximately 6 - 8 weeks from Baseline), Post-chemotherapy (approximately 2 - 3 weeks after the participant completed chemotherapy or approximately 14 - 18 weeks from Baseline)
Serum NF-L Levels	Changes in serum NFL levels over the course of chemotherapy will be monitored to determine if NFL can be used as a biomarker for axonal damage in patients who develop CIPN. NFL will be measured at baseline, before each round of chemotherapy and at the completion of chemotherapy. Changes in NFL will be compared between patients who develop CIPN and those that do not.	1 year

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: Disarm Therapeutics
• Investigators: Principal Investigator: Victoria H Lawson, M.D., Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): February 14, 2022
• Study Completion (Actual): February 14, 2022

Study Registration Dates

• First Submitted: October 19, 2017
• First Submitted That Met QC Criteria: November 16, 2017
• First Posted (Actual): November 21, 2017

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Neuromuscular Diseases; Poisoning; Peripheral Nervous System Diseases; Neurotoxicity Syndromes
• Other Study ID Numbers: D17062

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data is not intended to be shared with other researchers per the current protocol and informed consent.

Drug and device information, study documents

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