Lidocaine for Oxaliplatin-induced Neuropathy

The Washington University

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Drug: Placebo; Drug: FOLFOX regimen; Drug: Lidocaine Hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT03254394

201705166

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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26 participants in 2 patient groups, including a placebo group

Placebo + FOLFOX

Placebo Comparator group

Description:

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.

Treatment:

Drug: FOLFOX regimen

Drug: Placebo

Lidocaine + FOLFOX

Active Comparator group

Description:

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.

Treatment:

Drug: FOLFOX regimen

Drug: Lidocaine Hydrochloride