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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Neurotoxicity

Treatments: Dietary Supplement: vitamin E; Other: placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00363129

NCCTG-N05C3

CDR0000491071 (Registry Identifier)

NCI-2011-01712 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 207 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Required Characteristics:

1. 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).

2. ≥ 18 years of age

3. Ability to sign informed consent and understand the nature of a placebo-controlled trial

4. ECOG Performance Status (PS) of 0, 1, or 2 e.g.

5. Ability to complete questionnaire(s) by themselves or with assistance

6. Life expectancy ≥ 6 months

Contraindications:

1. Undergoing chemotherapy for palliative care

2. Pre-existing history of peripheral neuropathy due to any cause (diabetes, alcohol, toxin, hereditary, etc).

3. 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).

4. Taking regular opioid-containing medications. (Exception: opioids, given for the short term treatment of chemotherapy-induced myalgias or arthralgias caused by taxanes are permitted.)

5. 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.

6. 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.

7. Other medical conditions, which in the opinion of the treating physician/allied health professional would make this protocol unreasonably hazardous for the patient.

8. 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.)

9. Any of the following: pregnant women, nursing women and men or women of childbearing potential who are unwilling to employ adequate contraception

10. 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.

11. Diagnosed diabetes requiring insulin or oral hypoglycemic medications

12. Head or neck cancers

13. Scheduled to undergo radiation therapy while on study

14. History of hemorrhagic stroke

15. Patients receiving neo-adjuvant therapy

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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207 participants in 2 patient groups, including a placebo group

Arm I

Experimental group

Description:

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.

Treatment:

Dietary Supplement: vitamin E

Arm II

Placebo Comparator group

Description:

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.

Treatment:

Other: placebo