Lamotrigine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Pain; Neurotoxicity

Treatments: Drug: lamotrigine; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00068445

CDR0000322830 (Registry Identifier)

NCCTG-N01C3

Details and patient eligibility

About

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.

Full 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.

Enrollment: 131 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

131 participants in 2 patient groups

Arm I - lamotrigine

Experimental group

Description:

Patients receive oral lamotrigine once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks in the absence of unacceptable toxicity. Quality of life, pain, mood states, and symptom distress are assessed at baseline and at 4, 6, 8, and 10 weeks. Patients are followed at 3-7 days.

Treatment:

Drug: lamotrigine

Arm II - placebo

Other group

Description:

Patients receive oral placebo once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks in the absence of unacceptable toxicity. Quality of life, pain, mood states, and symptom distress are assessed at baseline and at 4, 6, 8, and 10 weeks. Patients are followed at 3-7 days.

Treatment:

Other: Placebo