Wynnewood,
Pennsylvania
19096
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.
Study summary:
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.
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