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

NCT ID: NCT00112996

Last Updated: 2014-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 244 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2014-04-30

Brief 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.

Detailed 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.

Conditions

Neurotoxicity; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

Arm I: Alpha-Lipoic Acid

Oral alpha-lipoic acid three times daily for at least 24 weeks in the absence of unacceptable toxicity.

Group Type: EXPERIMENTAL

alpha-lipoic acid

Intervention Type: DRUG

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.

Arm II: Placebo

Oral placebo three times daily for at least 24 weeks in the absence of unacceptable toxicity.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

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

Interventions

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.

Intervention Type: DRUG

placebo

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ying Guo, MD, MS

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center

Fort Smith, Arkansas, United States

Horizon Oncology Center

Lafayette, Indiana, United States

CCOP - Wichita

Wichita, Kansas, United States

Cabrini Center for Cancer Care at Christus St. Frances Cabrini Hospital

Alexandria, Louisiana, United States

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Cancer Research for the Ozarks

Springfield, Missouri, United States

CCOP - Columbia River Oncology Program

Portland, Oregon, United States

CCOP - Main Line Health

Wynnewood, Pennsylvania, United States

CCOP - Greenville

Greenville, South Carolina, United States

University of Texas M.D. Anderson CCOP Research Base

Houston, Texas, United States

CCOP - Scott and White Hospital

Temple, Texas, United States

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States

Countries

United States

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

MDA-CCC-0327

Identifier Type: -

Identifier Source: secondary_id

MDA-2004-0728

Identifier Type: -

Identifier Source: secondary_id

2004-0728

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-00636

Identifier Type: REGISTRY

Identifier Source: secondary_id

3U10CA045809-15S1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000403155

Identifier Type: -

Identifier Source: org_study_id

NCT00705029

Identifier Type: -

Identifier Source: nct_alias