Lidocaine for Oxaliplatin-induced Neuropathy

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.

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