Pyridoxine and Topical Urea/Lactic Acid-Based Cream in Preventing Hand-Foot Syndrome in Patients Receiving Capecitabine for Breast Cancer or Other Cancer

Study Overview
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Brief Summary
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RATIONALE: Pyridoxine (vitamin B6) and topical urea/lactic acid-based cream may prevent or lessen hand-foot syndrome caused by chemotherapy. It is not yet known whether giving pyridoxine with or without topical urea/lactic acid-based cream is more effective than topical urea/lactic acid-based cream alone or a placebo in preventing hand-foot syndrome. PURPOSE: This randomized phase III trial is studying pyridoxine and topical urea/lactic acid-based cream to see how well they work compared with giving pyridoxine together with a placebo, giving topical urea/lactic acid-based cream together with a placebo, or giving two placebos in preventing hand-foot syndrome in patients who are receiving capecitabine for breast cancer or other cancer.

Detailed Description
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OBJECTIVES: Determine whether the prophylactic use of a topical urea/lactic acid cream can decrease the incidence/severity of capecitabine-caused palmar-plantar erythrodysesthesia in patients receiving capecitabine for breast and/or other cancer. Evaluate the potential toxicity of this cream. Determine whether the prophylactic use of vitamin B6 can decrease the incidence and/or severity of capecitabine-caused palmar-plantar erythrodysesthesia. Evaluate the potential toxicity of vitamin B6. Determine whether the prophylactic use of a topical urea/lactic acid cream in combination with vitamin B6 can decrease the incidence and/or severity of capecitabine caused palmar-plantar erythrodysesthesia. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to age (< 50 years old vs 50-60 years old vs > 60 years old), sex, capecitabine dose level (2000 mg/day vs 2500 mg/day), cancer type (breast vs other), and mode of therapy (adjuvant [including neo-adjuvant] therapy vs metastatic disease). Patients are randomized to 1 of 6 treatment arms (treatment arms I-IV closed to accrual as of 10/24/007). Arm I (closed to accrual as of 10/24/2007): Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily and oral pyridoxine once daily on days 1-21. Arm II (closed to accrual as of 10/24/2007): Patients receive topical urea/lactic acid-based cream as in arm I (closed to accrual as of 10/24/2007) and oral placebo once daily on days 1-21. Arm III (closed to accrual as of 10/24/2007): Patients receive placebo cream applied to palms and soles twice daily and pyridoxine as in arm I (closed to accrual as of 10/24/2007). Arm IV (closed to accrual as of 10/24/2007):Patients receive placebo cream as in arm III and oral placebo as in arm II (closed to accrual as of 10/24/2007). Arm V: Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21. Arm VI: Patients receive placebo cream applied to palms and soles twice daily on days 1-21. In all arms, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Official Title
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A Phase III Randomized, Placebo-controlled, Double-blind Trial to Determine the Effectiveness of a Urea/Lactic Acid-Based Topical Keratolytic Agent and Vitamin B-6 for Prevention of Capecitabine-Induced Hand and Foot Syndrome

Conditions
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Breast Cancer, Drug/Agent Toxicity by Tissue/Organ, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Dietary Supplement: pyridoxine hydrochloride
* Drug: urea/lactic acid-based topical cream
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed breast and/or other cancer Undergoing first treatment with capecitabine as adjuvant (including neo-adjuvant) therapy OR for metastatic disease Receiving a dose of capecitabine either 2,000 mg/day (1,000 mg twice daily) OR 2,500 mg/day for 14 days with 4 courses of therapy at 3 week (+/- 3 days) intervals Hormone-receptor status not specified PATIENT CHARACTERISTICS: Male or female Menopausal status not specified No history of allergy to urea-containing cream No pre-existing neuropathy ≥ grade 2 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: No other concurrent agents that function to prevent palmar-plantar erythrodysesthesia caused by capecitabine or topical agents in the hands or feet for other indications (e.g., dryness) No concurrent vitamin B6 > 50 mg/day No concurrent or planned use of over-the-counter products that contain urea or lactic acid, including any of the following: Aqua Care® Medicated Calamine^® lotion (0.3%) Coppertone^® Waterproof Ultra Protection Sunblock Dr. Scholl's^® Smooth Touch deep moisturizing cream Depicure^® So Smooth Cream Dove^® Moisturizing Cream Wash Cetaphil^ ®Moisturizing Cream Vaseline Intensive Care ^ ® lotion

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (closed to accrual as of 10/24/2007)<br>Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily and oral pyridoxine once daily on days 1-21. | Dietary Supplement: pyridoxine hydrochloride<br>* Given orally<br>Drug: urea/lactic acid-based topical cream<br>* Applied topically<br>|
| Experimental: Arm II (closed to accrual as of 10/24/2007)<br>Patients receive topical urea/lactic acid-based cream as in arm I (closed to accrual as of 10/24/2007) and oral placebo once daily on days 1-21. | Drug: urea/lactic acid-based topical cream<br>* Applied topically<br>Other: placebo<br>* Given orally or applied topically<br>|
| Experimental: Arm III (closed to accrual as of 10/24/2007)<br>Patients receive placebo cream applied to palms and soles twice daily and pyridoxine as in arm I (closed to accrual as of 10/24/2007). | Dietary Supplement: pyridoxine hydrochloride<br>* Given orally<br>Other: placebo<br>* Given orally or applied topically<br>|
| Placebo Comparator: Arm IV (closed to accrual as of 10/24/2007)<br>Patients receive placebo cream as in arm III and oral placebo as in arm II (closed to accrual as of 10/24/2007). | Other: placebo<br>* Given orally or applied topically<br>|
| Experimental: Arm V<br>Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21. | Drug: urea/lactic acid-based topical cream<br>* Applied topically<br>|
| Placebo Comparator: Arm VI<br>Patients receive placebo cream applied to palms and soles twice daily on days 1-21. | Other: placebo<br>* Given orally or applied topically<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine Whether the Prophylactic Use of a Topical Urea/Lactic Acid Cream Can Decrease the Incidence/Severity of Capecitabine-caused Palmar-plantar Erythrodysesthesia | A patient self-reported hand-foot syndrome (HFSD), also known as palmar-plantar erythrodysesthesia, was completed daily while applying the cream. Patients rated skin severity symptoms individually in their hands and in their feet. Definitions of symptoms, which were based on Common Terminology Criteria for Adverse Events (CTCAE) v3.0, were provided to patients. The number of patients reporting moderate to severe symptoms in either hands or feet were tabulated and percentages are reported. | First 3 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Evaluate the Potential Toxicity of Urea/Lactic Acid Cream | Frequency and severity of adverse events reported by patients in weekly diary and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report. | Up to 4, 21-day cycles | 
| Determine Whether the Prophylactic Use of Vitamin B6 Can Decrease the Incidence and/or Severity of Capecitabine-caused Palmar-plantar Erythrodysesthesia (HFSD). | A patient self-reported hand-foot syndrome diary (HFSD) was completed daily while applying the cream. Patients rated skin severity symptoms individually in their hands and in their feet. Definitions of symptoms, which were based on Common Terminology Criteria for Adverse Events (CTCAE) v3.0, were provided to patients. The number of patients reporting moderate to severe symptoms were tabulated and percentages are reported. | First 3 weeks of treatment | 
| Evaluate the Potential Toxicity of Vitamin B6. | Frequency and severity of adverse events reported by patients in weekly diary and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report. | up to 4, 21-day cycles | 
| Determine Whether the Prophylactic Use of a Topical Urea/Lactic Acid Cream in Combination With Vitamin B6 Can Decrease the Incidence and/or Severity of Capecitabine Caused Palmar-plantar Erythrodysesthesia. | A patient self-reported hand-foot syndrome diary (HFSD) was completed daily while applying the cream. Patients rated skin severity symptoms individually in their hands and in their feet. Definitions of symptoms, which were based on Common Terminology Criteria for Adverse Events (CTCAE) v3.0, were provided to patients. The number of patients reporting moderate to severe symptoms were tabulated. | First 3 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug/agent toxicity by tissue/organ, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, unspecified adult solid tumor, protocol specific