Lidocaine for Oxaliplatin-induced Neuropathy

NCT03254394 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 201705166
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Oxaliplatin-induced neuropathy is a major dose-limiting side effect in patients with colorectal cancer treated with the FOLFOX chemotherapy regimen. Hypersensitivity to cold is the sensory hallmark of oxaliplatin-induced neuropathy, and it can predict the development of long-term neuropathy. In this study, the investigators aim to determine whether intravenous lidocaine can prevent oxaliplatin-induced cold hypersensitivity.

Conditions

Neuropathy, Painful; Chemotherapy-induced Peripheral Neuropathy; Colorectal Cancer

Keywords

Oxaliplatin; Cold hypersensitivity; Neuropathy; Colorectal cancer; CIPN; Neuropathic Pain

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve (AUC) of Intensity of Oxaliplatin-induced Cold Pain/Unpleasantness vs Time

  The intensity of cold pain and cold unpleasantness is evaluated separately, assessed daily on a 0-10 scale, upon holding a pre-cooled (\~8°C) metal cylinder for 10 seconds. the area under the curve of cold pain and cold unpleasantness vs time is calculated per chemotherapy cycle (every two weeks) and serves as a primary outcome measure. For intervention (lidocaine+FOLFOX) and control (placebo+FOLFOX) groups, the average of cold pain AUC and cold unpleasantness AUC over 7 cycles was calculated. The average AUCs over 7 cycles were compared between study arms. The AUC is measured as a score on a 0-10 scale multiplied by 14 days and may range between 0 and 140. Higher AUC values represent more intense cold pain/unpleasantness.

  14 weeks

Secondary Outcomes (3)

• CIPN Score on EORTC QLQ-CIPN20

  12 weeks and 34-36 weeks

• Changes in NPSI Score.

  6 weeks, 12 weeks, 34-36 weeks

• The Cumulative Dose of Oxaliplatin

  24 weeks

Study Arms (2)

Placebo + FOLFOX

PLACEBO COMPARATOR

Intravenous infusion of D5W solution over a 130 minute period. FOLFOX: Oxaliplatin 85mg/m2 IV over 2h, Leucovorin 400 mg/m2 IV over 2h, 5-FU 400mg/m2 IV bolus, followed by a 1200mg/m2/day continuous infusion for 2 days.

Drug: Placebo; Drug: FOLFOX regimen

Lidocaine + FOLFOX

ACTIVE COMPARATOR

Intravenous infusion of lidocaine hydrochloride solution in D5W over a 130 minute period. FOLFOX: Oxaliplatin 85mg/m2 IV over 2h, Leucovorin 400 mg/m2 IV over 2h, 5-FU 400mg/m2 IV bolus, followed by a 1200mg/m2/day continuous infusion for 2 days.

Drug: Lidocaine Hydrochloride; Drug: FOLFOX regimen

Interventions

Lidocaine Hydrochloride DRUG

Intravenous lidocaine will be dosed as a brief 1 mg/kg infusion (based on Ideal Body Weight (IBW)) over 10 minutes, followed by a 0.04 mg/kg/min infusion over additional 120 minutes, resulting in a total dose of 5.8 mg/kg IBW. If this dose is tolerable in four consecutive sessions of mFOLFOX6 in six or more of the eight patients in the tolerability phase, we will initiate the randomized efficacy pilot study.

Lidocaine + FOLFOX

Placebo DRUG

Dextrose 5% in water will be administered as active comparator.

Placebo + FOLFOX

FOLFOX regimen DRUG

Each cycle (repeated every 14 days): Oxaliplatin 85mg/m2 IV over 2h, Leucovorin 400 mg/m2 IV over 2h, 5-FU 400mg/m2 IV bolus, followed by a 1200mg/m2/day continuous infusion for 2 days.

Also known as: mFOLFOX6

Lidocaine + FOLFOX; Placebo + FOLFOX

Eligibility Criteria

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

You may qualify if:

• Stage III and IV colorectal cancer.
• Scheduled for oxaliplatin treatment in mFOLFOX6-based chemotherapy regimen.
• Able to understand and willing to sign an IRB-approved written informed consent document.

You may not qualify if:

• Renal insufficiency (defined as calculated Creatinine clearance \< 30mL/min)
• Moderate to severe liver failure (defined as ALT or AST \> 3 times upper limit of normal if no liver metastases are present; ALT or AST \> 5 times upper limit of normal if liver metastases are present).
• Presence of brain metastases.
• Patients with currently uncontrolled cardiac arrhythmias (non-sinus rhythm).
• Patients with history of arrhythmias under pharmacological/pacemaker control will be allowed, except if receiving antiarrhythmic medication listed in "contra-indicated medications".
• Contraindication or allergy to intravenous lidocaine.
• Pre-existing symmetric peripheral painful neuropathy.
• Treated with chemotherapy within the past 12 months.
• Pregnancy or breastfeeding
• Currently treated with any of the following contraindicated medications: Saquinavir, Lopinavir, Amprenavir, Atazanavir, Delavirdine, Mexiletine (and other types of sodium-channel blocker antiarrhythmics), Phenytoin, Carbamazepine, Oxcarbazepine, Lamotrigine, Amiodarone, Dronedarone, Dihydroergotamine, Cimetidine

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine/Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Related Publications (4)

• Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, Colvin LA, Fallon M. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain. 2014 Dec;155(12):2461-2470. doi: 10.1016/j.pain.2014.09.020. Epub 2014 Sep 23.

  PMID: 25261162 BACKGROUND

• Attal N, Rouaud J, Brasseur L, Chauvin M, Bouhassira D. Systemic lidocaine in pain due to peripheral nerve injury and predictors of response. Neurology. 2004 Jan 27;62(2):218-25. doi: 10.1212/01.wnl.0000103237.62009.77.

  PMID: 14745057 BACKGROUND

• Attal N, Gaude V, Brasseur L, Dupuy M, Guirimand F, Parker F, Bouhassira D. Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Neurology. 2000 Feb 8;54(3):564-74. doi: 10.1212/wnl.54.3.564.

  PMID: 10680784 BACKGROUND

• Ventzel L, Madsen CS, Jensen AB, Jensen AR, Jensen TS, Finnerup NB. Assessment of acute oxaliplatin-induced cold allodynia: a pilot study. Acta Neurol Scand. 2016 Feb;133(2):152-155. doi: 10.1111/ane.12443. Epub 2015 Jun 2.

  PMID: 26032776 RESULT

MeSH Terms

Conditions

Neuropathy, Painful; Colorectal Neoplasms; Cold Hypersensitivity; Neuralgia

Interventions

Lidocaine; Folfox protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Limitations and Caveats

Due to the COVID-19 pandemic, the study finished earlier than planned. The total number of patients enrolled was 26 instead of 30.

Results Point of Contact

• Title: Simon Haroutounian, PhD. Associate Professor
• Organization: Washington University in St Louis

sharout@wustl.edu

3132861715

Study Officials

• Simon Haroutounian, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: At enrollment, each patient will be assigned a study number, which will match a previously prepared computer-generated list of randomization numbers to determine the interventions. The participants and all other study personnel will be blinded to the treatment allocation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology

Model Details: Tolerability phase: prospective, open-label Efficacy pilot study: randomized, parallel, double blind, placebo controlled

Study Record Dates

• First Submitted: August 9, 2017
• First Posted: August 18, 2017
• Study Start: September 15, 2017
• Primary Completion: September 28, 2020
• Study Completion: April 1, 2021
• Last Updated: March 9, 2022
• Results First Posted: March 9, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 6 months after publication
• Access Criteria: IPD will be shared 6 months after publication of the results in a peer-reviewed journal, upon submission of a robust data analysis plan to the study investigators.

Locations

US (1)