Trial Information

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

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.