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Lidocaine for Oxaliplatin-induced Neuropathy

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ClinicalTrials.gov Identifier: NCT03254394
Recruitment Status : Recruiting
First Posted : August 18, 2017
Last Update Posted : January 15, 2019
Sponsor:
Information provided by (Responsible Party):
simon.haroutounian, Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE August 9, 2017
First Posted Date  ICMJE August 18, 2017
Last Update Posted Date January 15, 2019
Actual Study Start Date  ICMJE September 15, 2017
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 15, 2017)
Intensity of oxaliplatin-induced cold hypersensitivity [ Time Frame: 12 weeks ]
The intensity of cold hypersensitivity, assessed on a 0-10 scale, upon holding a pre--cooled (~8°C) metal cylinder, will serve as primary outcome measure. Comparison between intervention (lidocaine) and placebo after 6 cycles of oxaliplatin.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03254394 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2018)
  • CIPN score on EORTC QLQ-CIPN20 [ Time Frame: 12 weeks and 34-36 weeks ]
    Change in CIPN score (on EORTC QLQ-CIPN20 tool ) over time until last follow-up
  • Changes in NPSI. [ Time Frame: 6 weeks, 12 weeks, 34-36 weeks ]
    Changes in NPSI descriptors of neuropathic pain over time from baseline to last follow-up.
  • The cumulative dose of oxaliplatin [ Time Frame: 24 weeks ]
    The cumulative dose of oxaliplatin received over the course (up to 12 cycles) of mFOLFOX6.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2017)
  • Occurence of Grade 2+ peripheral Neuropathy [ Time Frame: 12 weeks ]
    The occurrence of Grade 2+ peripheral neuropathy , measured by NCI-CTC Peripheral Neuropathy Grading, compared between arms after 6 cycles of oxaliplatin.
  • CIPN score on EORTC QLQ-CIPN20 [ Time Frame: 12 weeks and 34-36 weeks ]
    Change in CIPN score (on EORTC QLQ-CIPN20 tool ) over time until last follow-up
  • Sensory changes on QST [ Time Frame: 6 weeks, 12 weeks, 34-36 weeks. ]
    The magnitude of sensory disturbances on qunatitative sensory testing QST (change from baseline to last follow-up.
  • Changes in NPSI. [ Time Frame: 6 weeks, 12 weeks, 34-36 weeks ]
    Changes in NPSI descriptors of neuropathic pain over time from baseline to last follow-up.
  • The cumulative dose of oxaliplatin [ Time Frame: 24 weeks ]
    The cumulative dose of oxaliplatin received over the course (up to 12 cycles) of mFOLFOX6.
  • Progression-free survival [ Time Frame: 2 years ]
    Two-year progression-free survival determined by medical record review.
  • Overall survival [ Time Frame: 2 years ]
    Two-year overall survival determined by medical record review.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lidocaine for Oxaliplatin-induced Neuropathy
Official Title  ICMJE Intravenous Lidocaine for Preventing Painful Oxaliplatin-induced Peripheral Neuropathy (OIPN)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Tolerability phase: prospective, open-label Efficacy pilot study: randomized, parallel, double blind, placebo controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
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.
Primary Purpose: Prevention
Condition  ICMJE
  • Neuropathy, Painful
  • Chemotherapy-induced Peripheral Neuropathy
  • Colorectal Cancer
Intervention  ICMJE
  • Drug: Lidocaine Hydrochloride

    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.

  • Drug: Placebo
    Dextrose 5% in water will be administered as active comparator.
  • Drug: FOLFOX regimen

    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.

    Other Name: mFOLFOX6
Study Arms  ICMJE
  • Placebo Comparator: Placebo + FOLFOX

    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.

    Interventions:
    • Drug: Placebo
    • Drug: FOLFOX regimen
  • Active Comparator: Lidocaine + FOLFOX

    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.

    Interventions:
    • Drug: Lidocaine Hydrochloride
    • Drug: FOLFOX regimen
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 15, 2017)
38
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Simon Haroutounian, PhD 314 286 1715 haroutos@anest.wustl.edu
Contact: Karen Frey, BS 314 454 5980 freyk@anest.wustl.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03254394
Other Study ID Numbers  ICMJE 201705166
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party simon.haroutounian, Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Simon Haroutounian, PhD Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP