Gabapentin in Treating Peripheral Neuropathy in Cancer Patients Undergoing Chemotherapy

The Efficacy Of Gabapentin In The Management Of Chemotherapy-Induced Peripheral Neuropathy: A Phase III Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

RATIONALE: Gabapentin may be effective in relieving pain and other symptoms of peripheral neuropathy. It is not yet known if gabapentin is effective in treating peripheral neuropathy in cancer patients undergoing chemotherapy.

PURPOSE: Randomized phase III trial to determine the effectiveness of gabapentin in treating pain and other symptoms of peripheral neuropathy in cancer patients undergoing chemotherapy.

Study Overview

• Status: Completed
• Conditions: Pain; Neurotoxicity
• Intervention / Treatment: Other: placebo; Drug: gabapentin

Detailed Description

OBJECTIVES:

• Determine whether gabapentin improves the pain and other symptoms in cancer patients with chemotherapy-induced peripheral neuropathy.
• Determine the effect of this drug on symptom distress, mood states, functional abilities, and overall quality of life in these patients.
• Determine the toxic effects of this drug in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to neurotoxic chemotherapy (active vs nonactive and discontinued vs completed) and neurotoxic chemotherapeutic agents (vinca alkaloids vs taxanes vs platinum-based compounds vs combination of two or more of the above agents). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive titrating doses of oral gabapentin twice daily and then three times daily for 3 weeks. Patients then receive a fixed dose of oral gabapentin three times daily for 3 weeks. Patients cross-over to therapy as in arm II at week 8.
• Arm II: Patients receive titrating doses of oral placebo and then a fixed dose of oral placebo as in arm I. Patients cross-over to therapy as in arm I at week 8.

Quality of life is assessed at baseline and then at the end of weeks 6, 8, and 14.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5404
      • CCOP - Mayo Clinic Scottsdale Oncology Program
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Peoria, Illinois, United States, 61602
      • CCOP - Illinois Oncology Research Association
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403-1206
      • CCOP - Cedar Rapids Oncology Project
    • Des Moines, Iowa, United States, 50309-1016
      • CCOP - Iowa Oncology Research Association
    • Sioux City, Iowa, United States, 51101-1733
      • Siouxland Hematology-Oncology
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • CCOP - Ochsner
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Health Plaza
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
  • North Dakota
    • Bismarck, North Dakota, United States, 58501-5505
      • Medcenter One Health System
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center
  • Ohio
    • Toledo, Ohio, United States, 43623-3456
      • CCOP - Toledo Community Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • CCOP - Oklahoma
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • South Dakota
    • Rapid City, South Dakota, United States, 57709
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57104
      • CCOP - Sioux Community Cancer Consortium
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • CCOP - St. Vincent Hospital Cancer Center, Green Bay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Has received or is currently receiving neurotoxic chemotherapy, including taxanes (e.g., paclitaxel or docetaxel), platinum-based compounds (e.g., carboplatin, cisplatin, or oxaliplatin), or vinca alkaloids (e.g., vincristine or vinblastine)

• Pain or symptoms of peripheral neuropathy of at least 1 month duration attributed to chemotherapy-induced peripheral neuropathy

  • Average daily pain rating of at least 4 out of 10 using the pain numerical rating scale (where 0 is no pain and 10 is the worst pain possible) OR

  • Evidence of peripheral neuropathy of at least grade 1 out of 3 by ECOG Common

    • Toxicity Criteria for sensory neuropathy

• No other identified causes of painful paresthesia existing prior to chemotherapy

  • No radiotherapy-induced or malignant plexopathy
  • No lumbar or cervical radiculopathy

  • No pre-existing peripheral neuropathy of another etiology, including:

    • B12 deficiency
    • AIDS
    • Monoclonal gammopathy
    • Diabetes
    • Heavy metal poisoning
    • Amyloidosis
    • Syphilis
    • Hyperthyroidism or hypothyroidism
    • Inherited neuropathy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Life expectancy:

• At least 6 months

Renal:

• Creatinine no greater than 1.5 times upper limit of normal

Other:

• No prior allergic reaction or intolerance to gabapentin
• No significant psychiatric illness (e.g., mania, psychosis, or schizophrenia) that would preclude study compliance
• No extreme difficulty swallowing pills
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Other:

• More than 30 days since prior investigational agent for pain control
• Concurrent selective serotonin reuptake inhibitors allowed
• Concurrent nonsteroidal anti-inflammatory drugs allowed
• No concurrent tricyclic antidepressant (e.g., amitriptyline, nortriptyline, or desipramine)*
• No concurrent monoamine oxidase inhibitor*
• No concurrent opioid analgesic*
• No other concurrent adjuvant analgesic (e.g., anticonvulsant, clonazepam, or mexiletine)*
• No concurrent topical analgesics (e.g., lidocaine gel or lidocaine patch)*
• No concurrent amifostine
• No concurrent investigational agent for pain control NOTE: * For pain or symptoms due to chemotherapy-induced peripheral neuropathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: gabapentin; Patients receive titrating doses of oral gabapentin twice daily and then three times daily for 3 weeks. Patients then receive a fixed dose of oral gabapentin three times daily for 3 weeks. Patients cross-over to therapy as in arm II at week 8. Quality of life is assessed at baseline and then at the end of weeks 6, 8, and 14.	Drug: gabapentin
Placebo Comparator: placebo; Patients receive titrating doses of oral placebo and then a fixed dose of oral placebo as in arm I. Patients cross-over to therapy as in arm I at week 8. Quality of life is assessed at baseline and then at the end of weeks 6, 8, and 14.	Other: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in pain and symptoms	Up to 14 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Quality of life	Up to 14 weeks

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Rao RD, Michalak JC, Sloan JA, Loprinzi CL, Soori GS, Nikcevich DA, Warner DO, Novotny P, Kutteh LA, Wong GY; North Central Cancer Treatment Group. Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled, crossover trial (N00C3). Cancer. 2007 Nov 1;110(9):2110-8. doi: 10.1002/cncr.23008.

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: December 7, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 4, 2016
• Last Update Submitted That Met QC Criteria: July 1, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: pain; neurotoxicity
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Neuromuscular Diseases; Poisoning; Peripheral Nervous System Diseases; Neurotoxicity Syndromes; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: NCCTG-N00C3; CDR0000069098 (Registry Identifier: PDQ (Physician Data Query)); NCCTG-CCC-0020; NCI-P01-0196