Pyridoxine in Preventing Hand-Foot Syndrome Caused by Capecitabine in Patients With Cancer

Study Overview
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Brief Summary
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RATIONALE: Pyridoxine may help prevent hand-foot syndrome caused by capecitabine in patients with cancer. It is not yet known whether pyridoxine is more effective than a placebo in preventing hand-foot syndrome in patients with cancer. PURPOSE: This randomized phase III trial is studying pyridoxine to see how well it works compared with a placebo in preventing hand-foot syndrome caused by capecitabine in patients with cancer.

Detailed Description
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OBJECTIVES: Primary Compare the incidence of capecitabine-induced palmar-plantar erythrodysesthesia (hand-foot syndrome [HFS]) ≥ grade 2 in patients with cancer treated with pyridoxine hydrochloride vs placebo. Secondary Compare the time to onset of HFS ≥ grade 2 in patients treated with these regimens. Compare the quality of life changes in patients treated with these regimens. Identify factors predicting toxicity from capecitabine chemotherapy. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to gender and treatment setting (adjuvant/neoadjuvant vs palliative setting). Patients are randomized to 1 of 2 treatment arms. Arm I: Beginning concurrently with planned capecitabine treatment, patients receive oral pyridoxine hydrochloride once daily on days 1-21. Arm II: Beginning concurrently with planned capecitabine treatment, patients receive oral placebo once daily on days 1-21. In both arms, treatment repeats every 21 days for up to 8 courses (until discontinuation of capecitabine treatment). Quality of life is assessed at baseline, at the beginning of courses 2, 4, 6, and 8, and at the end of the study.

Official Title
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Randomized Double-Blind Placebo-Controlled Trial of Pyridoxine for Prevention of Capecitabine-Induced Hand-Foot Syndrome (HFS)

Conditions
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Dermatologic Complications, Palmar-plantar Erythrodysesthesia, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Dietary Supplement: pyridoxine hydrochloride
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of cancer Must be receiving single-agent capecitabine either in the adjuvant/neoadjuvant or palliative setting at a dose of ≥ 1000 mg/m² twice daily on days 1-14 (given in 3-week courses) PATIENT CHARACTERISTICS: Life expectancy > 12 weeks No preexisting neuropathy No known allergy to pyridoxine hydrochloride and its incipients No other dermatologic condition that, in the opinion of the physician, may affect the hands or feet or may complicate evaluation during study treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior capecitabine Concurrent radiotherapy, steroids, and/or biological therapy (e.g., trastuzumab [Herceptin®] or bevacizumab) allowed provided they do not cause hand-foot syndrome (HFS) No other concurrent drugs (e.g., docetaxel or doxorubicin hydrochloride liposome) that can cause HFS No concurrent drugs (e.g., oxaliplatin or taxanes) that can cause neuropathy No concurrent pyridoxine hydrochloride-containing preparations (e.g., multivitamins or vitamin B complex) No concurrent over-the-counter products that contain urea or lactic acid No concurrent drugs reported to have drug interactions with pyridoxine hydrochloride (e.g., cycloserine; hydralazine; immunosuppressants; isoniazid; levodopa; estrogen or estrogen-containing contraceptives; penicillamine; phenobarbitone; phenytoin; or pyrazinamide)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pyridoxine hydrochloride<br>Pyridoxine (200mg) or placebo once daily orally for 21 days out of each treatment cycle | Dietary Supplement: pyridoxine hydrochloride<br>* Pyridoxine (200mg) or placebo once daily orally for 21 days out of each treatment cycle<br>|
| Placebo Comparator: Placebo<br>Pyridoxine (200mg) or placebo once daily orally for 21 days out of each treatment cycle | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First incidence of hand-foot syndrome (HFS) ≥ grade 2 according to NCI CTCAE vs 3.0 |  | up to 8 cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the onset of HFS ≥ grade 2 |  | days to weeks | 
| Quality of life as measured by EuroQOL (EQ-5D) questionnaire |  | QOL assessment at baseline, at beginning of cycles 2, 4, 6, 8 and at the end of the study. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dermatologic complications, chemotherapeutic agent toxicity, palmar-plantar erythrodysesthesia, unspecified adult solid tumor, protocol specific