Clinical trial NCT00112996: Alpha-Lipoic Acid in Preventing Peripheral Neuropathy in Patients Receiving Chemotherapy for Cancer
Official title: Prevention of Cisplatin- or Oxaliplatin-Induced Peripheral Neuropathy With Alpha-Lipoic Acid: A Placebo-Controlled Phase III Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neurotoxicity
Unspecified Adult Solid Tumor, Protocol Specific
Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: neurotoxicity
unspecified adult solid tumor, protocol specific
unspecified childhood solid tumor, protocol specific
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-06-03
Enrollment: 244
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility 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

Primary outcomes:
measure: Severity of neuropathy
timeFrame: Up to 48 weeks
Secondary outcomes:
measure: Group Differences in Change scores
timeFrame: Up to 48 weeks
measure: Number of courses received
timeFrame: Up 48 weeks
measure: Optimal tumor response
timeFrame: Up to 48 weeks
Other outcomes:
Locations:
city: Fort Smith
country: United States
facility: Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
state: Arkansas
city: Lafayette
country: United States
facility: Horizon Oncology Center
state: Indiana
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Alexandria
country: United States
facility: Cabrini Center for Cancer Care at Christus St. Frances Cabrini Hospital
state: Louisiana
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: St. Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Springfield
country: United States
facility: Cancer Research for the Ozarks
state: Missouri
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Wynnewood
country: United States
facility: CCOP - Main Line Health
state: Pennsylvania
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Houston
country: United States
facility: University of Texas M.D. Anderson CCOP Research Base
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Ying Guo, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: