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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

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

Intervention / Treatment
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* Drug: alpha-lipoic acid
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I: Alpha-Lipoic Acid<br>Oral alpha-lipoic acid three times daily for at least 24 weeks in the absence of unacceptable toxicity. | Drug: alpha-lipoic acid<br>* 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.<br>|
| Placebo Comparator: Arm II: Placebo<br>Oral placebo three times daily for at least 24 weeks in the absence of unacceptable toxicity. | Other: placebo<br>* Given orally two similar color and sized placebo control tablets three times a day continued for 24 weeks.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurotoxicity, unspecified adult solid tumor, protocol specific, unspecified childhood solid tumor, protocol specific