Clinical trial NCT03254394: Lidocaine for Oxaliplatin-induced Neuropathy
Official title: Intravenous Lidocaine for Preventing Painful Oxaliplatin-induced Peripheral Neuropathy (OIPN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neuropathy, Painful
Chemotherapy-induced Peripheral Neuropathy
Colorectal Cancer
Keywords: Oxaliplatin
Cold hypersensitivity
Neuropathy
Colorectal cancer
CIPN
Neuropathic Pain
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2017-08-18
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Tolerability phase: prospective, open-label Efficacy pilot study: randomized, parallel, double blind, placebo controlled
Primary purpose: PREVENTION

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.

Detailed description: Colorectal cancer is the third leading cause of cancer death in the United States, with an estimated incidence of 130.000 cases per year. Oxaliplatin is the first-line chemotherapy regimen for gastro-intestinal cancers. Despite its efficacy, oxaliplatin causes peripheral neuropathy in 72% of the treated patients. Acute oxaliplatin-induced peripheral neuropathy \[OIPN\] is the most common dose-limiting side effect of oxaliplatin and characterized by profound cold allodynia in the extremities. In about 21% of the patients acute OIPN exacerbates into chronic neuropathic pain, which is treatment resistant to currently approved drugs, pointing towards a great need to identify an effective strategy in preventing OIPN. Recent literature suggests that certain methods of assessing sensory nerve function in neuropathic pain patients may provide a prediction to an individual analgesic response; however, no placebo-controlled studies have been performed with the primary goal of identifying treatment response predictors in preventing OIPN.

In this pilot study we will both determine the tolerability and the efficacy of intravenous Lidocaine, for preventing oxaliplatin-induced cold hypersensitivity in the setting of mFOLFOX6 chemotherapy for advanced colorectal cancer.

The proposed study will be conducted in two phases. The tolerability phase is an open-label study to determine the tolerable dose regimen of IV lidocaine in patients with advanced colorectal cancer receiving oxaliplatin chemotherapy. The efficacy pilot phase is a randomized, double-blinded, controlled study comparing the outcomes between IV lidocaine versus placebo in the same setting of colorectal cancer. Consented subjects will attend a screening visit and six intervention visits, during which they will undergo sensory testing and receive intravenous lidocaine or placebo infusion. Cold hypersensitivity and spontaneous pain will be assessed at baseline, daily for 12 weeks and at follow-up visits. 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 lidocaine or placebo. The participants and all other study personnel will be blinded to the treatment allocation.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Area Under the Curve (AUC) of Intensity of Oxaliplatin-induced Cold Pain/Unpleasantness vs Time
timeFrame: 14 weeks
Secondary outcomes:
measure: CIPN Score on EORTC QLQ-CIPN20
timeFrame: 12 weeks and 34-36 weeks
measure: Changes in NPSI Score.
timeFrame: 6 weeks, 12 weeks, 34-36 weeks
measure: The Cumulative Dose of Oxaliplatin
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine/Barnes Jewish Hospital
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Simon Haroutounian, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.