Official Title: “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”

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.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Placebo Control

Study Primary Completion Date: December 2009

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.

PROJECTED ACCRUAL: A total of 132 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Dietary Supplement: pyridoxine hydrochloride
  • Given orally
• Drug: urea/lactic acid-based topical cream
  • Applied topically
• Other: placebo
  • Given orally or applied topically

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 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.
• Experimental: 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.
• Experimental: 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).
• Placebo Comparator: 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).
• Experimental: Arm V
  • Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.
• Placebo Comparator: Arm VI
  • Patients receive placebo cream applied to palms and soles twice daily on days 1-21.

Primary Measures

• Percentage of patients with ≥ moderate hand and/or foot symptoms as assessed by patient daily diary vs physician
  • Safety Issue?: No

Secondary Measures

• Percentage of patients with ≥ mild hand and/or foot symptoms as assessed by patient daily diary vs physician
  • Safety Issue?: No
• Percentage of patients with ≥ severe hand and/or foot symptoms as assessed by patient daily diary vs physician
  • Safety Issue?: No
• Mean maximum score of hand and/or foot symptoms as assessed by patient daily diary vs physician
  • Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: North Central Cancer Treatment Group

Overall Clinical Trial Officials and Contacts

Charles L. Loprinzi, MD Study Chair Mayo Clinic  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00296036

Study ID Number: CDR0000464246

ClinicalTrials.gov Identifier: NCT00296036

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database