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

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Neurotoxicity
• Intervention / Treatment: Other: placebo; Dietary supplement: vitamin E

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Bloomington, Illinois, United States, 61701
      • St. Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Eureka, Illinois, United States, 61530
      • Eureka Community Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Clinic, PC
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates, Limited - West
    • Kewanee, Illinois, United States, 61443
      • Kewanee Hospital
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Community Hospital of Ottawa
    • Ottawa, Illinois, United States, 61350
      • Oncology Hematology Associates of Central Illinois, PC - Ottawa
    • Peoria, Illinois, United States, 61615
      • CCOP - Illinois Oncology Research Association
    • Peoria, Illinois, United States, 61615
      • Oncology Hematology Associates of Central Illinois, PC - Peoria
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center at Carle Foundation Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Centers
  • Iowa
    • Ottumwa, Iowa, United States, 52501
      • McCreery Cancer Center at Ottumwa Regional
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Jackson, Michigan, United States, 49201
      • Foote Memorial Hospital
    • Lansing, Michigan, United States, 48912-1811
      • Sparrow Regional Cancer Center
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute at Saint Mary's - Saginaw
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Lichfield, Minnesota, United States, 55355
      • Meeker County Memorial Hospital
    • Mankato, Minnesota, United States, 56002
      • Immanuel St. Joseph's
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology, PA - Maplewood
    • Maplewood, Minnesota, United States, 55109
      • HealthEast Cancer Care at St. John's Hospital
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center - Minneapolis
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Shakopee, Minnesota, United States, 55379
      • St. Francis Cancer Center at St. Francis Medical Center
    • St Paul, Minnesota, United States, 55102
      • HealthEast Cancer Care at St. Joseph's Hospital
    • St. Paul, Minnesota, United States, 55102
      • United Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology, PA - Woodbury
    • Woodbury, Minnesota, United States, 55125
      • HealthEast Cancer Care at Woodwinds Health Campus
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Bismarck Cancer Center
    • Bismarck, North Dakota, United States, 58501
      • Medcenter One Hospital Cancer Care Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, PC
  • Ohio
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Columbus, Ohio, United States, 43214-3998
      • Riverside Methodist Hospital Cancer Care
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health - West Hospital
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital at Ohio Health
    • Columbus, Ohio, United States, 43215
      • Grant Riverside Cancer Services
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Marietta, Ohio, United States, 45750
      • Strecker Cancer Center at Marietta Memorial Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Cancer Care Program at Licking Memorial Hospital
    • Springfield, Ohio, United States, 45505
      • Community Hospital of Springfield and Clark County
    • Springfield, Ohio, United States, 45504
      • Mercy Medical Center
    • Westerville, Ohio, United States, 43081
      • Mount Carmel St. Ann's Cancer Center
    • Zanesville, Ohio, United States, 43701
      • Genesis - Good Samaritan Hospital
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center, PC
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Cancer Center at Sanford USD Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; 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; Given orally
Placebo Comparator: Arm II; 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; Given orally

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Lisa Kottschade, RN, MSN, CNP, Mayo Clinic

Publications and helpful links

General Publications

• Kottschade LA, Sloan JA, Mazurczak MA, Johnson DB, Murphy BP, Rowland KM, Smith DA, Berg AR, Stella PJ, Loprinzi CL. The use of vitamin E for the prevention of chemotherapy-induced peripheral neuropathy: results of a randomized phase III clinical trial. Support Care Cancer. 2011 Nov;19(11):1769-77. doi: 10.1007/s00520-010-1018-3. Epub 2010 Oct 9.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: August 10, 2006
• First Submitted That Met QC Criteria: August 10, 2006
• First Posted (Estimate): August 15, 2006

Study Record Updates

• Last Update Posted (Estimate): July 6, 2016
• Last Update Submitted That Met QC Criteria: July 1, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific; neurotoxicity
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Neuromuscular Diseases; Poisoning; Peripheral Nervous System Diseases; Neurotoxicity Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E
• Other Study ID Numbers: NCCTG-N05C3; NCI-2011-01712 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000491071 (Registry Identifier: PDQ (Physician Data Query))