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

NCT00068445 | Completed Phase 3 Results DMC

• 2 other identifiers: NCCTG-N01C3CDR0000322830
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 23

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.

Conditions

Neurotoxicity; Pain; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

neurotoxicity; pain; unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (2)

• Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS)

  The change in mean score for average daily pain from baseline to week 10 using the Pain Intensity Rating (NRS) are reported below. The NRS scale ranges from 0 to 10 with higher scores corresponding to having more pain.

  From baseline to week 10

• Change in Average Pain Score as Measured Using the European Cooperative Oncology Group (ECOG) Neuropathy Scale (ENS)

  The change in mean score for average daily pain from baseline to week 10 using the European Cooperative Oncology Group (ECOG) neuropathy scale (ENS) are reported below. The ENS scale goes from 0 to 3 with 0=none, 1=mild paresthesias, 2=mild or moderate sensory loss and/or moderate paresthesias, and 3=severe sensory loss or paresthesias that interfere with function.

  From baseline to week 10

Secondary Outcomes (8)

• The Change in Overall Quality of Life as Measured by the Uniscale QOL From Baseline to Week 10

  From baseline to week 10

• Change in Brief Pain Inventory (BPI) Worst Pain Score [Week 10 Minus Baseline]

  From baseline to week 10

• Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline]

  From baseline to week 10

• Change in Brief Pain Inventory (BPI) Average Pain Score [Week 10 Minus Baseline]

  From baseline to week 10

• Change in Brief Pain Inventory (BPI) Pain Now Score [Week 10 Minus Baseline]

  From baseline to week 10

Study Arms (2)

Arm I - lamotrigine

EXPERIMENTAL

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.

Drug: lamotrigine

Arm II - placebo

OTHER

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.

Other: Placebo

Interventions

lamotrigine DRUG

Arm I - lamotrigine

Placebo OTHER

Arm II - placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (23)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

CCOP - Atlanta Regional

Atlanta, Georgia, 30342-1701, United States

Location

MBCCOP - Hawaii

Honolulu, Hawaii, 96813, United States

Location

CCOP - Illinois Oncology Research Association

Peoria, Illinois, 61615-7828, United States

Location

CCOP - Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, 52403-1206, United States

Location

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, 50309-1854, United States

Location

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

Sioux City, Iowa, 51101-1733, United States

Location

CCOP - Wichita

Wichita, Kansas, 67214-3882, United States

Location

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, 48106, United States

Location

CCOP - Duluth

Duluth, Minnesota, 55805, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Coborn Cancer Center

Saint Cloud, Minnesota, 56303, United States

Location

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Cancer Care Center at Medcenter One Hospital

Bismarck, North Dakota, 58501-5505, United States

Location

CCOP - Dayton

Dayton, Ohio, 45429, United States

Location

CCOP - Toledo Community Hospital

Toledo, Ohio, 43623-3456, United States

Location

CCOP - Upstate Carolina

Spartanburg, South Carolina, 29303, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57709, United States

Location

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, 57104, United States

Location

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, 54301, United States

Location

Related Publications (1)

• 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.

  PMID: 18428211 RESULT

MeSH Terms

Conditions

Neurotoxicity Syndromes; Pain

Interventions

Lamotrigine

Condition Hierarchy (Ancestors)

Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Charles L. Loprinzi, M.D.
• Organization: Mayo Clinic

cloprinzi@mayo.edu

507-284-3731

Study Officials

• Ravi D. Rao, MD, MBBS

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2003
• First Posted: September 11, 2003
• Study Start: February 1, 2004
• Primary Completion: May 1, 2006
• Study Completion: November 1, 2013
• Last Updated: May 4, 2018
• Results First Posted: May 4, 2018

Record last verified: 2018-04

Locations

US (23)