Clinical trial NCT00068445: Lamotrigine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
Official title: The Efficacy of Lamotrigine in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Phase III Randomized, Double Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neurotoxicity
Pain
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: neurotoxicity
pain
unspecified adult solid tumor, protocol specific
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-09-11
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Lamotrigine may be effective in reducing pain, numbness, tingling, and other symptoms of peripheral neuropathy. It is not yet known whether lamotrigine is effective in treating peripheral neuropathy caused by chemotherapy.

PURPOSE: This randomized phase III trial is studying how well lamotrigine works in reducing pain, numbness, tingling, and other symptoms of peripheral neuropathy caused by chemotherapy in patients with cancer.

Detailed description: OBJECTIVES:

* Compare the efficacy of lamotrigine vs placebo in reducing pain and symptoms of chemotherapy-induced peripheral neuropathy in patients with cancer.
* Compare symptom distress, mood states, functional abilities, and overall quality of life of patients treated with these agents.
* Determine the toxic effects of lamotrigine in these patients.

OUTLINE: This is a randomized, placebo-controlled, double-blind study. Patients are stratified according to neurotoxic chemotherapy received (taxanes vs platinum-based compounds vs vinca alkaloids vs combination vs other), status of neurotoxic chemotherapy (actively receiving therapy vs discontinued or completed), and duration of pain or neuropathy symptoms (1-3 months vs 3-6 months vs more than 6 months). Patients are randomized to 1 of 2 treatment arms.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of cancer
* Received, or are currently receiving, neurotoxic chemotherapy, including any of the following:

  * Taxanes (e.g., paclitaxel or docetaxel)
  * Platinum-based compounds (e.g., carboplatin, cisplatin, or oxaliplatin)
  * Vinca alkaloids (e.g., vincristine or vinblastine)
* Experiencing pain or symptoms of peripheral neuropathy for at least 1 month attributed to chemotherapy

  * Average daily pain rating of at least 4 out of 10 OR
  * Peripheral neuropathy at least grade 1 out of 3 using ECOG sensory neuropathy rating

PATIENT CHARACTERISTICS:

Age

* 18 and over

Life expectancy

* At least 6 months

Hepatic

* Bilirubin \< 2 times upper limit of normal (ULN)

Renal

* Creatinine ≤ 1.5 times ULN

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No prior allergic reaction or intolerance to lamotrigine
* No extreme difficulty swallowing pills
* No other identified causes of painful paresthesia preceding chemotherapy, including any of the following:

  * Radiation or malignant plexopathy
  * Lumbar or cervical radiculopathy
  * Pre-existing peripheral neuropathy of another etiology, such as any of the following:

    * Cyanocobalamin deficiency
    * AIDS
    * Monoclonal gammopathy
    * Diabetes
    * Heavy metal poisoning amyloidosis
    * Syphilis
    * Hyperthyroidism or hypothyroidism
    * Inherited neuropathy
* No significant psychiatric illness (e.g., mania, psychosis, or schizophrenia) that would preclude study participation
* Able to complete questionnaires

PRIOR CONCURRENT THERAPY:

Chemotherapy

* See Disease Characteristics
* More than 7 days since prior methotrexate or other dihydrofolate inhibitors

Other

* More than 7 days since prior, and no concurrent use of any of the following:

  * Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, or desipramine)

    * Concurrent selective serotonin reuptake inhibitors allowed
  * Monoamine oxidase inhibitors
  * Opioid analgesics
  * Anticonvulsants (e.g., gabapentin, topiramate, valproic acid, or clonazepam)
  * Adjuvant analgesics (e.g., mexiletine)

    * Prior nonsteroidal anti-inflammatory drugs allowed
  * Topical analgesics (e.g., lidocaine gel or patch) to the affected area
  * Amifostine
* More than 30 days since prior investigational agents for pain control
* No other concurrent investigational agents for pain control

Primary outcomes:
measure: Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS)
timeFrame: From baseline to week 10
measure: Change in Average Pain Score as Measured Using the European Cooperative Oncology Group (ECOG) Neuropathy Scale (ENS)
timeFrame: From baseline to week 10
Secondary outcomes:
measure: The Change in Overall Quality of Life as Measured by the Uniscale QOL From Baseline to Week 10
timeFrame: From baseline to week 10
measure: Change in Brief Pain Inventory (BPI) Worst Pain Score [Week 10 Minus Baseline]
timeFrame: From baseline to week 10
measure: Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline]
timeFrame: From baseline to week 10
measure: Change in Brief Pain Inventory (BPI) Average Pain Score [Week 10 Minus Baseline]
timeFrame: From baseline to week 10
measure: Change in Brief Pain Inventory (BPI) Pain Now Score [Week 10 Minus Baseline]
timeFrame: From baseline to week 10
measure: Change in Brief Pain Inventory (BPI) Pain Relief Score [Week 10 Minus Baseline]
timeFrame: From baseline to week 10
measure: Change in Brief Pain Inventory (BPI) Pain Interference Score [Week 10 Minus Baseline]
timeFrame: From baseline to week 10
measure: Change in POMS Total Score [Week 10 Minus Baseline]
timeFrame: From baseline to week 10
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Atlanta
country: United States
facility: CCOP - Atlanta Regional
state: Georgia
city: Honolulu
country: United States
facility: MBCCOP - Hawaii
state: Hawaii
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Bismarck
country: United States
facility: Cancer Care Center at Medcenter One Hospital
state: North Dakota
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Ravi D. Rao, MD, MBBS
role: STUDY_CHAIR
References:
citation: Rao RD, Flynn PJ, Sloan JA, Wong GY, Novotny P, Johnson DB, Gross HM, Renno SI, Nashawaty M, Loprinzi CL. Efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled trial, N01C3. Cancer. 2008 Jun 15;112(12):2802-8. doi: 10.1002/cncr.23482.