Alpha-Lipoic Acid in Preventing Peripheral Neuropathy in Patients Receiving Chemotherapy for Cancer

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

Prevention of Cisplatin- or Oxaliplatin-Induced Peripheral Neuropathy With Alpha-Lipoic Acid: A Placebo-Controlled Phase III Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00112996
• Other study ID #: CDR0000403155
• Secondary ID: MDA-CCC-0327MDA-
• Status: Completed
• Phase: Phase 3
• First received: June 2, 2005
• Last updated: April 7, 2014
• Start date: January 2007
• Est. completion date: April 2014

Study information

• Verified date: April 2014
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as alpha-lipoic acid, may protect normal cells from the side effects of chemotherapy. Alpha-lipoic acid may also prevent damage to nerves that carry information to and from the brain and spinal cord to the rest of the body. It is not known whether alpha-lipoic acid is more effective than placebo in preventing peripheral neuropathy.

PURPOSE: This randomized phase III trial is studying alpha-lipoic acid to see how well it works compared to placebo in preventing peripheral neuropathy in patients receiving chemotherapy for cancer.

Description:

OBJECTIVES:

Primary

• Compare whether treatment with alpha-lipoic acid vs placebo decreases the severity and frequency of peripheral neuropathy in cancer patients receiving a cisplatin- or oxaliplatin-containing chemotherapy regimen.

• Compare the protective effect duration of these drugs in these patients.

Secondary

• Determine large sensory fiber integrity associated with platinum-induced peripheral neuropathy, as measured by three timed functional tests comprising fastening 6-buttons, walking 50 feet, and placing coins in a cup, in patients treated with these drugs.

• Compare the number of chemotherapy courses and doses received by patients treated with these drugs.

Tertiary

• Compare the optimal tumor response (disease progression, stable disease, partial response, or complete response) to chemotherapy in patients treated with these drugs.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to prior platinum-containing treatment (yes vs no). Patients who received prior treatment are further stratified according to prior cumulative platinum exposure (cisplatin < 200 mg/m^2 or oxaliplatin < 750 mg/m^2 vs cisplatin 200-399 mg/m^2 or oxaliplatin 750-999 mg/m^2 vs cisplatin >400 mg/m^2 or oxaliplatin > 1,000 mg/m^2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral alpha-lipoic acid* three times daily for at least 24 weeks in the absence of unacceptable toxicity.

• Arm II: Patients receive oral placebo* three times daily for at least 24 weeks in the absence of unacceptable toxicity.

NOTE: *In both arms, patients begin taking study drug 4 days after completion of each chemotherapy treatment and continue taking study drug until 2 days before their next scheduled chemotherapy treatment.

Patients' symptoms of peripheral neuropathy, pain, and functional tests are assessed at baseline and then at weeks 6-8, 12, 24, 36, and 48.

PROJECTED ACCRUAL: A total of 244 patients (122 per treatment arm) will be accrued for this study within 2 years.

Other known NCT identifiers

• NCT00705029

Recruitment information / eligibility

• Status: Completed
• Enrollment: 244
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS:

• Scheduled to receive a cisplatin- or oxaliplatin-containing chemotherapy regimen for cancer

• No established clinical neuropathy

• No clinically evident CNS metastases, including leptomeningeal metastases

PATIENT CHARACTERISTICS:

Age

• Not specified

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin < 2 mg/dL

Renal

• Creatinine < 2 mg/dL OR

• Creatinine clearance > 45 mL/min

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Must have a normal state of arousal

• No confusion or memory or concentration deficit

• No history of diabetes mellitus requiring oral medication or insulin treatment

• No chronic alcoholism

• No other active central nervous system (CNS) disease (e.g., dementia or encephalopathy)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

• No carboplatin, vincristine, vinblastine, paclitaxel, or docetaxel for 6 months prior, during, and 6 months after study treatment

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• Concurrent medications that can modify peripheral neuropathy (e.g., gabapentin, lamotrigine, carbamazepine, phenytoin, or tricyclic antidepressants) are allowed provided there is no dose adjustment within 2 weeks before study entry and during study participation

• No concurrent vitamin E (including multivitamins that contain vitamin E) = 100 IU per day

• No concurrent physical modality (e.g., anodyne [monochromatic near-infrared photoenergy, 890 nm], microcurrent, or transcutaneous electrical neural stimulation) for peripheral neuropathy related symptoms unless physical or occupational therapy for functional training

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• alpha-lipoic acid
Oral two 300 mg ALA sustained release tablets initiated 4 days after last dose of platinum and discontinued 2 days before next scheduled platinum dose, continued for 24 weeks.

Other:
• placebo
Given orally two similar color and sized placebo control tablets three times a day continued for 24 weeks.

Locations

Country	Name	City	State
United States	Cabrini Center for Cancer Care at Christus St. Frances Cabrini Hospital	Alexandria	Louisiana
United States	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center	Fort Smith	Arkansas
United States	CCOP - Greenville	Greenville	South Carolina
United States	University of Texas M.D. Anderson CCOP Research Base	Houston	Texas
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	Horizon Oncology Center	Lafayette	Indiana
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Cancer Research for the Ozarks	Springfield	Missouri
United States	CCOP - Metro-Minnesota	St. Louis Park	Minnesota
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	CCOP - Wichita	Wichita	Kansas
United States	CCOP - Main Line Health	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Severity of neuropathy	Severity of neuropathy as measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity Questionnaire total score at baseline and at 6-8, 12, 24, 36, and 48 weeks	Up to 48 weeks	No
Secondary	Group Differences in Change scores	Group differences in change scores from baseline at 6-8, 12, 24, 36, and 48 weeks	Up to 48 weeks	No
Secondary	Number of courses received		Up 48 weeks	No
Secondary	Optimal tumor response		Up to 48 weeks	No

External Links

•   University of Texas MD Anderson Cancer Center Website