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

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00363129
• Other study ID #: NCCTG-N05C3
• Secondary ID: NCI-2011-01712CD
• Status: Completed
• Phase: Phase 3
• First received: August 10, 2006
• Last updated: July 1, 2016
• Start date: December 2006
• Est. completion date: August 2014

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 207
• Est. completion date: August 2014
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Neurotoxicity
• Neurotoxicity Syndromes
• Peripheral Nervous System Diseases
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Dietary Supplement:
• vitamin E
Given orally

Other:
• placebo
Given orally

Locations

Country	Name	City	State
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Riverside Cancer Services	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Eureka Community Hospital	Eureka	Illinois
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Mason District Hospital	Havana	Illinois
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Kewanee Hospital	Kewanee	Illinois
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Meeker County Memorial Hospital	Lichfield	Minnesota
United States	Immanuel St. Joseph's	Mankato	Minnesota
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Mercy Medical Center	Springfield	Ohio
United States	HealthEast Cancer Care at St. Joseph's Hospital	St Paul	Minnesota
United States	United Hospital	St. Paul	Minnesota
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	St. John Macomb Hospital	Warren	Michigan
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. S — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Percentage of Patients Requiring Dose Reductions of Chemotherapy Due to Sensory Peripheral Neuropathy		6 months post completion of chemotherapy treatment	Yes
Secondary	Percentage of Patients Stopping Chemotherapy Before Treatment is Complete Due to Sensory Peripheral Neuropathy		6 months post completion of chemotherapy treatment	Yes
Secondary	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	Yes
Secondary	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	Yes