Vitamin E in Preventing Peripheral Neuropathy Caused by Chemotherapy in Patients Receiving Chemotherapy for Cancer

Study Overview
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Brief Summary
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RATIONALE: Vitamin E may prevent peripheral neuropathy caused by chemotherapy in patients with cancer. It is not yet known whether vitamin E is more effective than a placebo in preventing peripheral neuropathy caused by chemotherapy in patients receiving chemotherapy for cancer. PURPOSE: This randomized phase III trial is studying vitamin E to see how well it works compared with placebo in preventing peripheral neuropathy caused by chemotherapy in patients receiving chemotherapy for cancer.

Detailed Description
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OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to type of chemotherapy (taxane vs cisplatin vs carboplatin vs oxaliplatin vs combination), age (≤ 50 years vs > 50 years), and gender. Patients are randomized to 1 of 2 treatment arms. OBJECTIVES: Primary Compare the incidence of chemotherapy-induced sensory peripheral neuropathy ≥ grade 2 in patients undergoing curative neurotoxic chemotherapy for cancer treated with vitamin E vs placebo. Secondary Compare the proportion of patients requiring dose reductions of chemotherapy secondary to sensory peripheral neuropathy. Compare the proportion of patients stopping chemotherapy before treatment is complete secondary to sensory peripheral neuropathy. Assess the toxicity of vitamin E in these patients. After completion of study treatment, patients are followed at 6 months.

Official Title
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The Use of Vitamin E for Prevention of Chemotherapy Induced Peripheral Neuropathy: A Phase III Double-Blind Placebo Controlled Study

Conditions
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Neurotoxicity, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Dietary Supplement: vitamin E
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Required Characteristics: Scheduled to undergo curative-intent adjuvant treatment with neurotoxic chemotherapy. Patients must have had his/her tumor removed, but may have microscopic residual disease, or residual margin involvement and still be eligible. The patient's chemotherapy regimen must include one or more of the following neurotoxic chemotherapeutic agents: taxanes (paclitaxel, docetaxel); platinum compounds (cisplatin, carboplatin, oxaliplatin)-(oxaliplatin patients should preferentially be enrolled in protocol N04C7 while it is available). ≥ 18 years of age Ability to sign informed consent and understand the nature of a placebo-controlled trial ECOG Performance Status (PS) of 0, 1, or 2 e.g. Ability to complete questionnaire(s) by themselves or with assistance Life expectancy ≥ 6 months Contraindications: Undergoing chemotherapy for palliative care Pre-existing history of peripheral neuropathy due to any cause (diabetes, alcohol, toxin, hereditary, etc). Prior treatment with neurotoxic chemotherapy (exception: Patient started neurotoxic chemotherapy ≤ 4 days of starting vitamin E on this study and has not been treated previously with other neurotoxic chemotherapy agents). Taking regular opioid-containing medications. (Exception: opioids, given for the short term treatment of chemotherapy-induced myalgias or arthralgias caused by taxanes are permitted.) Concurrent treatment with anticonvulsants, tricyclic antidepressants, or other neuropathic pain medications agents such as carbamazepine, phenytoin, valproic acid, gabapentin, lamotrigine, topical lidocaine patch, capsaicin cream, etc. History of coronary artery disease (i.e. MI, PTCA, or CABG ≤ 5 years or diagnosis of congestive heart failure of any NY heart class I-IV) Valve replacements are permitted as long as patient has fully recovered from the surgery. Other medical conditions, which in the opinion of the treating physician/allied health professional would make this protocol unreasonably hazardous for the patient. Vitamin E supplementation for any reason ≤ 7 days prior to randomization. (Exception: one multivitamin per day that contains ≤ 100 IU [mg] of Vitamin E, will be permitted.) Any of the following: pregnant women, nursing women and men or women of childbearing potential who are unwilling to employ adequate contraception Taking anticoagulant medication (i.e. coumadin, low molecular weight heparin (LMWH), or platelet aggregation inhibitors such as clopidgrel or aspirin) with the exception that 1 mg/day of coumadin for central line maintenance is allowed. Diagnosed diabetes requiring insulin or oral hypoglycemic medications Head or neck cancers Scheduled to undergo radiation therapy while on study History of hemorrhagic stroke Patients receiving neo-adjuvant therapy

Ages Eligible for Study
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Minimum Age: 18 Years

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral vitamin E twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy. | Dietary Supplement: vitamin E<br>* Given orally<br>|
| Placebo Comparator: Arm II<br>Patients receive oral placebo twice daily beginning within 4 days of the start of chemotherapy course 1 and continuing until 1 month after completion of chemotherapy. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Chemotherapy-induced Sensory Peripheral Neuropathy ≥ Grade 2 | The chemotherapy-induced sensory peripheral neuropathy utilized the sensory neuropathy item from the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grading: Grade 0=none; grade 1=loss of deep tendon reflexes or paresthesia, including tingling, but not interfering with function; grade 2=objective sensory alteration or paresthesia, including tingling, interfering with function, but not with activities of daily living; grade 3=sensory alteration or paresthesia interfering with activities of daily living; grade 4=permanent sensory losses that are disabling; and grade 5=death. | 6 months post completion of chemotherapy treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Requiring Dose Reductions of Chemotherapy Due to Sensory Peripheral Neuropathy |  | 6 months post completion of chemotherapy treatment | 
| Percentage of Patients Stopping Chemotherapy Before Treatment is Complete Due to Sensory Peripheral Neuropathy |  | 6 months post completion of chemotherapy treatment | 
| Time to Onset of Sensory Peripheral Neuropathy ≥ Grade 2 | Time to onset of sensory peripheral neuropathy was calculated using incidences of the adverse event while the patient was receiving chemotherapy. | 6 months post completion of chemotherapy treatment | 
| Duration of Sensory Peripheral Neuropathy ≥ Grade 2 | Duration of sensory peripheral neuropathy is the time from onset of grade 2+ neuropathy until the neuropathy is resolved to grade 1 or less during chemotherapy treatment. | 6 months post completion of chemotherapy treatment | 

 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