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

NCT ID: NCT00068445

Last Updated: 2018-05-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2013-11-30

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.

Conditions

Neurotoxicity; Pain; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

Arm I - lamotrigine

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.

Group Type: EXPERIMENTAL

lamotrigine

Intervention Type: DRUG

Arm II - placebo

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.

Group Type: OTHER

Placebo

Intervention Type: OTHER

Interventions

lamotrigine

Intervention Type: DRUG

Placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ravi D. Rao, MD, MBBS

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

CCOP - Atlanta Regional

Atlanta, Georgia, United States

MBCCOP - Hawaii

Honolulu, Hawaii, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center

Sioux City, Iowa, United States

CCOP - Wichita

Wichita, Kansas, United States

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

CCOP - Duluth

Duluth, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Coborn Cancer Center

Saint Cloud, Minnesota, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Cancer Care Center at Medcenter One Hospital

Bismarck, North Dakota, United States

CCOP - Dayton

Dayton, Ohio, United States

CCOP - Toledo Community Hospital

Toledo, Ohio, United States

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States

Rapid City Regional Hospital

Rapid City, South Dakota, United States

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 18428211 (View on PubMed)

Other Identifiers

CDR0000322830

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCCTG-N01C3

Identifier Type: -

Identifier Source: org_study_id