Biomarkers in Chemotherapy-Induced Peripheral Neurotoxicity

NCT03348956 | Completed Results DMC FDA Device

• 1 other identifier: D17062
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

CIPN - Chemotherapy-Induced Peripheral Neuropathy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (44)

• Neurologic Examination_ Strength_ Toe Fan

  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

  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

  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

  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

  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)

Study Arms (1)

EPR Oximetry

EXPERIMENTAL

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

Interventions

EPR Oximetry DIAGNOSTIC_TEST

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.

EPR Oximetry

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• Disarm Therapeutics: collaborator

Study Sites (1)

Dartmouth-Hitchcock Medical Center in Lebanon, NH

Lebanon, New Hampshire, 03766, United States

Location

Limitations and Caveats

LIMITATION OF EPR DATA While it may be feasible to make serial measurements with the technique, there were technical problems with the sensor (India Ink), and no conclusions can be drawn in regard to oxygenation. Additionally, the ERP data are limited.

Results Point of Contact

• Title: Victoria Lawson
• Organization: Dartmouth Hitchcock Medical Center

victoria.h.lawson@hitchcock.org

(603) 650-5104

Study Officials

• Victoria H Lawson, M.D.

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Study Record Dates

• First Submitted: October 19, 2017
• First Posted: November 21, 2017
• Study Start: March 1, 2018
• Primary Completion: February 14, 2022
• Study Completion: February 14, 2022
• Last Updated: June 20, 2024
• Results First Posted: June 20, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)