Prevention of Cisplatin- or Oxaliplatin-Induced Peripheral Neuropathy With Alpha-Lipoic Acid: A Placebo-Controlled Phase III Trial
N/A
N/A
Both
Neurotoxicity, Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific
Trial Information
Prevention of Cisplatin- or Oxaliplatin-Induced Peripheral Neuropathy With Alpha-Lipoic Acid: A Placebo-Controlled Phase III Trial
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Supportive Care
Outcome Measure:
Severity of neuropathy
Outcome Description:
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
Outcome Time Frame:
Up to 48 weeks
Safety Issue:
No
Principal Investigator
Ying Guo, MD, MS
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000403155
NCT ID:
NCT00112996
Start Date:
January 2007
Completion Date:
December 2011
Related Keywords:
- Neurotoxicity
- Unspecified Adult Solid Tumor, Protocol Specific
- Unspecified Childhood Solid Tumor, Protocol Specific
- neurotoxicity
- unspecified adult solid tumor, protocol specific
- unspecified childhood solid tumor, protocol specific
- Peripheral Nervous System Diseases
- Neurotoxicity Syndromes
- Neoplasms
Name | Location |
|---|---|
| CCOP - Wichita | Wichita, Kansas 67214-3882 |
| CCOP - Kalamazoo | Kalamazoo, Michigan 49007-3731 |
| CCOP - Metro-Minnesota | Saint Louis Park, Minnesota 55416 |
| Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin 54449 |
| Cancer Research for the Ozarks | Springfield, Missouri 65807 |
| CCOP - Greenville | Greenville, South Carolina 29615 |
| CCOP - Columbia River Oncology Program | Portland, Oregon 97225 |
| CCOP - Scott and White Hospital | Temple, Texas 76508 |
| Hembree Mercy Cancer Center at St. Edward Mercy Medical Center | Ft. Smith, Arkansas 72903 |
| CCOP - Main Line Health | Wynnewood, Pennsylvania 19096 |
| University of Texas M.D. Anderson CCOP Research Base | Houston, Texas 77030-4009 |
| Horizon Oncology Center | Lafayette, Indiana 47905 |
| Cabrini Center for Cancer Care at Christus St. Frances Cabrini Hospital | Alexandria, Louisiana 71301 |
