Treatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil
The primary objective is to evaluate whether topical sildenafil reduces the severity of hand
foot syndrome or palmar plantar erythrodysesthesia (PPE) associated with sunitinib and
capecitabine. The secondary objective is to describe any toxicities associated with topical
This is a randomized, double blind, placebo-controlled pilot study of topical sildenafil for
patients with grade 1-3 hand foot syndrome related to chemotherapeutic agents.
Approximately 20 evaluable patients with grade 1-3 PPE will be treated with topical
- 10 patients with PPE related to sunitinib
- 10 patients with PPE related to capecitabine
Once eligibility and screening criteria are met, subjects will be given 2 types of topical
cream, one containing 1% sildenafil citrate and one containing placebo control. Subjects
will be randomized to apply sildenafil citrate cream to either the right or left hand/foot;
placebo cream will be applied to the opposite hand/ foot.
Clinical history, physical examination and photography of the hands and feet will be
performed every two weeks for the first 2 months for patients on sunitinib and then every
4-6 weeks thereafter. For patients on capecitabine (which is given on an every 3 week
schedule), these evaluations will be done every 3 weeks. Additional visits may be performed
if clinically indicated.
If PPE resolves, less frequent administration and lower doses will be permitted to maintain
responses. For consistency, patients may first reduce treatment to twice per day at the
dose at which the PPE resolved. If this dosing schedule is effective then lower
concentrations, e.g. 0.5%, may be used.
Patient cream assignment will be un-blinded at the 8 or 9 week time period (depending on the
chemotherapy). However, patients with a 2 grade improvement in PPE in one hand versus the
other (e.g. grade 3 improves to grade 1, or grade 2 improves to grade 0) that is maintained
for at least 2 weeks, will be eligible for early un-blinding and treatment with active
sildenafil for both hands and both feet.
Patients may receive topical sildenafil for up to 6 months on study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Grade of hand foot syndrome over time as measured by NCI CTC version 4.0 PPE syndrome criteria
Grading of PPE by NCI CTC criteria occurs every 2 weeks for subjects in the sunitinib arm for 1st 8 weeks (and as clinically indicated). Grading of PPE by NCI CTC criteria occurs every 3 weeks for subjects in the capeccitabine arm for the 1st 9 weeks (and as clinically indicated)
Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)
Herbert Hurwitz, MD
United States: Institutional Review Board
|Duke University Medical Center||Durham, North Carolina 27710|