Alpha-Lipoic Acid in Preventing Peripheral Neuropathy in Patients Receiving Chemotherapy for Cancer

Prevention of Cisplatin- or Oxaliplatin-Induced Peripheral Neuropathy With Alpha-Lipoic Acid: A Placebo-Controlled Phase III Trial

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as alpha-lipoic acid, may protect normal cells from the side effects of chemotherapy. Alpha-lipoic acid may also prevent damage to nerves that carry information to and from the brain and spinal cord to the rest of the body. It is not known whether alpha-lipoic acid is more effective than placebo in preventing peripheral neuropathy.

PURPOSE: This randomized phase III trial is studying alpha-lipoic acid to see how well it works compared to placebo in preventing peripheral neuropathy in patients receiving chemotherapy for cancer.

Study Overview

• Status: Completed
• Conditions: Unspecified Childhood Solid Tumor, Protocol Specific; Unspecified Adult Solid Tumor, Protocol Specific; Neurotoxicity
• Intervention / Treatment: Drug: alpha-lipoic acid; Other: placebo

Detailed Description

OBJECTIVES:

Primary

• Compare whether treatment with alpha-lipoic acid vs placebo decreases the severity and frequency of peripheral neuropathy in cancer patients receiving a cisplatin- or oxaliplatin-containing chemotherapy regimen.
• Compare the protective effect duration of these drugs in these patients.

Secondary

• Determine large sensory fiber integrity associated with platinum-induced peripheral neuropathy, as measured by three timed functional tests comprising fastening 6-buttons, walking 50 feet, and placing coins in a cup, in patients treated with these drugs.
• Compare the number of chemotherapy courses and doses received by patients treated with these drugs.

Tertiary

• Compare the optimal tumor response (disease progression, stable disease, partial response, or complete response) to chemotherapy in patients treated with these drugs.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to prior platinum-containing treatment (yes vs no). Patients who received prior treatment are further stratified according to prior cumulative platinum exposure (cisplatin < 200 mg/m^2 or oxaliplatin < 750 mg/m^2 vs cisplatin 200-399 mg/m^2 or oxaliplatin 750-999 mg/m^2 vs cisplatin >400 mg/m^2 or oxaliplatin > 1,000 mg/m^2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral alpha-lipoic acid* three times daily for at least 24 weeks in the absence of unacceptable toxicity.
• Arm II: Patients receive oral placebo* three times daily for at least 24 weeks in the absence of unacceptable toxicity.

NOTE: *In both arms, patients begin taking study drug 4 days after completion of each chemotherapy treatment and continue taking study drug until 2 days before their next scheduled chemotherapy treatment.

Patients' symptoms of peripheral neuropathy, pain, and functional tests are assessed at baseline and then at weeks 6-8, 12, 24, 36, and 48.

PROJECTED ACCRUAL: A total of 244 patients (122 per treatment arm) will be accrued for this study within 2 years.

• Study Type: Interventional
• Enrollment (Actual): 244
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Fort Smith, Arkansas, United States, 72913
      • Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Center
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Cabrini Center for Cancer Care at Christus St. Frances Cabrini Hospital
  • Michigan
    • Kalamazoo, Michigan, United States, 49007-3731
      • CCOP - Kalamazoo
  • Minnesota
    • St. Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Missouri
    • Springfield, Missouri, United States, 65804
      • Cancer Research for the Ozarks
  • Oregon
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - Main Line Health
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
  • Texas
    • Houston, Texas, United States, 77030-4009
      • University of Texas M.D. Anderson CCOP Research Base
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Scheduled to receive a cisplatin- or oxaliplatin-containing chemotherapy regimen for cancer
• No established clinical neuropathy
• No clinically evident CNS metastases, including leptomeningeal metastases

PATIENT CHARACTERISTICS:

Age

• Not specified

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin < 2 mg/dL

Renal

• Creatinine < 2 mg/dL OR
• Creatinine clearance > 45 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Must have a normal state of arousal
• No confusion or memory or concentration deficit
• No history of diabetes mellitus requiring oral medication or insulin treatment
• No chronic alcoholism
• No other active central nervous system (CNS) disease (e.g., dementia or encephalopathy)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No carboplatin, vincristine, vinblastine, paclitaxel, or docetaxel for 6 months prior, during, and 6 months after study treatment

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• Concurrent medications that can modify peripheral neuropathy (e.g., gabapentin, lamotrigine, carbamazepine, phenytoin, or tricyclic antidepressants) are allowed provided there is no dose adjustment within 2 weeks before study entry and during study participation
• No concurrent vitamin E (including multivitamins that contain vitamin E) ≥ 100 IU per day
• No concurrent physical modality (e.g., anodyne [monochromatic near-infrared photoenergy, 890 nm], microcurrent, or transcutaneous electrical neural stimulation) for peripheral neuropathy related symptoms unless physical or occupational therapy for functional training

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I: Alpha-Lipoic Acid; Oral alpha-lipoic acid three times daily for at least 24 weeks in the absence of unacceptable toxicity.	Drug: alpha-lipoic acid; Oral two 300 mg ALA sustained release tablets initiated 4 days after last dose of platinum and discontinued 2 days before next scheduled platinum dose, continued for 24 weeks.
Placebo Comparator: Arm II: Placebo; Oral placebo three times daily for at least 24 weeks in the absence of unacceptable toxicity.	Other: placebo; Given orally two similar color and sized placebo control tablets three times a day continued for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of neuropathy	Severity of neuropathy as measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity Questionnaire total score at baseline and at 6-8, 12, 24, 36, and 48 weeks	Up to 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group Differences in Change scores	Group differences in change scores from baseline at 6-8, 12, 24, 36, and 48 weeks	Up to 48 weeks
Number of courses received		Up 48 weeks
Optimal tumor response		Up to 48 weeks

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ying Guo, MD, MS, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: June 2, 2005
• First Submitted That Met QC Criteria: June 2, 2005
• First Posted (Estimate): June 3, 2005

Study Record Updates

• Last Update Posted (Estimate): April 8, 2014
• Last Update Submitted That Met QC Criteria: April 7, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: unspecified childhood solid tumor, protocol specific; unspecified adult solid tumor, protocol specific; neurotoxicity
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Neuromuscular Diseases; Poisoning; Neoplasms; Peripheral Nervous System Diseases; Neurotoxicity Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin B Complex; Thioctic Acid
• Other Study ID Numbers: CDR0000403155; MDA-CCC-0327; MDA-2004-0728; 2004-0728 (Other Identifier: UT MD Anderson Cancer Center); NCI-2009-00636 (Registry Identifier: NCI CTRP); 3U10CA045809-15S1 (U.S. NIH Grant/Contract)