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

M.D. Anderson Cancer Center

Status and phase: Completed; Phase 3

Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Neurotoxicity; Unspecified Childhood Solid Tumor, Protocol Specific

Treatments: Other: placebo; Drug: alpha-lipoic acid

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00112996

2004-0728 (Other Identifier)

3U10CA045809-15S1 (U.S. NIH Grant/Contract)

MDA-CCC-0327

MDA-2004-0728

NCI-2009-00636 (Registry Identifier)

CDR0000403155

Details and patient eligibility

About

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.

Full 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.

Enrollment: 244 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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244 participants in 2 patient groups, including a placebo group

Arm I: Alpha-Lipoic Acid

Experimental group

Description:

Oral alpha-lipoic acid three times daily for at least 24 weeks in the absence of unacceptable toxicity.

Treatment:

Drug: alpha-lipoic acid

Arm II: Placebo

Placebo Comparator group

Description:

Oral placebo three times daily for at least 24 weeks in the absence of unacceptable toxicity.

Treatment:

Other: placebo