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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00112996
First received: June 2, 2005
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Neurotoxicity
Unspecified Adult Solid Tumor, Protocol Specific
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: alpha-lipoic acid
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
Official Title: Prevention of Cisplatin- or Oxaliplatin-Induced Peripheral Neuropathy With Alpha-Lipoic Acid: A Placebo-Controlled Phase III Trial

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Severity of neuropathy [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Group Differences in Change scores [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    Group differences in change scores from baseline at 6-8, 12, 24, 36, and 48 weeks

  • Number of courses received [ Time Frame: Up 48 weeks ] [ Designated as safety issue: No ]
  • Optimal tumor response [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]

Enrollment: 244
Study Start Date: January 2007
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112996

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

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00112996     History of Changes
Obsolete Identifiers: NCT00705029
Other Study ID Numbers: CDR0000403155, MDA-CCC-0327, MDA-2004-0728, 2004-0728, NCI-2009-00636, 3 U10 CA045809-15S1
Study First Received: June 2, 2005
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
neurotoxicity
unspecified adult solid tumor, protocol specific
unspecified childhood solid tumor, protocol specific

Additional relevant MeSH terms:
Neurotoxicity Syndromes
Neoplasms
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Thioctic Acid
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on October 19, 2014