Alpha-lipoic Acid in Patients at Risk for Paclitaxel Induced Neuropathy

Study Overview
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Brief Summary
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This study is being done because peripheral neuropathy, a condition that interrupts sensation in your limbs, is a common side effect of paclitaxel. There is some evidence that alpha lipoic acid (ALA), an antioxidant compound, protects neurons after exposure to paclitaxel. The purpose of this study is to assess the safety and tolerability of ALA and to find the best dose of ALA in patients that receive chemotherapy.

Official Title
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Dose Finding and Tolerability Study of Alpha-lipoic Acid in Patients at Risk for Paclitaxel Induced Peripheral Neuropathy

Conditions
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Peripheral Neuropathy

Intervention / Treatment
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* Drug: Alpha lipoic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Diagnosis of Breast cancer. Breast cancer must meet the following criteria: Early stage breast cancer (stages I, IIA) must be estrogen receptor (ER) positive AND low tumor grade (histopathologic grade 1 or 2) Locally advanced breast cancer (LABC) (stages IIB, IIIA, IIB as defined by the Union for International Cancer Control and American Joint Committee on Cancer) must be ER positive, HER2 positive or HER2 negative, AND satisfy the following requirements: high endocrine responsiveness (defined as greater than 50% of tumor cells staining for hormone receptors), Grade 1 or 2 histological grade, less than 4 nodes positive, absence of extensive peritumoral vascular invasion, AND pathological tumor size less than 5 cm. Inflammatory breast cancer (IBC) (stage IIIC) Metastatic breast cancer (stage IV) Must be receiving single agent paclitaxel in their prescribed chemotherapy regimen. Age > 18 years. There is no upper age limit for participation in this study. Required lab values: AST, ALT, creatinine Women of childbearing potential and sexually active males must agree to use contraception while on study. ECOG performance status 0,1,2 All patients must have given signed, informed consent. Exclusion Criteria Breast cancer meeting the following criteria: Breast cancer stage 0 Early stage breast cancer (stages I, IIA) that is ER negative OR higher tumor grade (histopathologic grade greater than 2) Stages I, II, and IIIA triple negative breast cancer (negative for estrogen receptors, progesterone receptors, and HER2) LABC (stages IIB, IIIA, IIB) if they have low endocrine responsiveness (defined as less than 50% of tumor cells staining for hormone receptors), Grade 3 histological grade, 4 or more nodes positive, presence of extensive peritumoral vascular invasion, OR pathological tumor size greater than 5 cm LABC (stages IIB, IIIA, IIB) that are ER negative Evidence of pre-existing peripheral neuropathy as determined by baseline Michigan neuropathy screening instrument score > 2. Previous chemotherapy treatment of any kind. AST and ALT >2 times upper limit of normal; Creatinine > 2.0 mg/dL. Current use of medications or substances known to be associated with peripheral neuropathy. Use of ALA or other anti-oxidant supplements during the prior three months. Diabetes mellitus or use of medications known to lower blood sugar. Participation in any other experimental trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alpha lipoic acid<br>Oral administration three times daily (morning, mid-day, night) | Drug: Alpha lipoic acid<br>* The baseline dose is 100 mg three times daily for four months. Dose escalation will occur until a maximum tolerated dose is found.<br>* Other names: Thioctic Acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of the Optimal Dose of ALA Based on Acceptable Adverse Event(AE) Profile | Based on acceptable adverse event (AE) profile and continual reassessment method dose escalation. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Complete the Proposed Regimen of Daily ALA |  | 4 months | 
| Cumulative Rate of Adverse Events |  | 4 months | 
| Total Neuropathy Score (TNS) | The Total Neuropathy score (TNS) is a validated score that combines signs, symptoms, and very limited nerve conduction studies (NCS). It was designed to assess peripheral nerve function and has been used as an endpoint in clinical trials of toxic neuropathy. The TNS is a composite scale with a range of values from 0 (normal) to 28 (severely affected). It includes data from 7 different categories. Patients are asked to assess the severity of sensory symptoms on a scale of 0 (no symptoms) to 4 (symptoms above knees or elbows, or functionally disabling). Next, 4 examination categories are assessed. These include pin sensation, vibration sensation, deep tendon reflexes, and strength. Signs are scored from 0 to 4 depending on severity. The nerve conduction portion of the scale consists of measurements of a motor (peroneal) and sensory (sural) nerve. Motor and sensory responses are graded on a scale of 0 to 4 depending on the severity of an abnormality. | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chemotherapy, peripheral neuropathy, paclitaxel, breast cancer