Treatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil
Condition: Hand Foot Syndrome; Palmar Plantar Erythrodysesthesia
MeSH terms: Hand-Foot Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysethesia (PPE), occurs in a
      25%-50% of patients treated with several commonly used anti-cancer drugs including
      capecitabine and sunitinib. These drugs are known to improve survival in many cancers,
      including cancers of the colon, stomach, liver, breast, kidney, and GI stromal tumors (GIST).
      Worldwide, over 400,000 patients per year are treated with one of these agents. HFS involves
      skin changes, such as swelling, peeling, and blistering of the palms and soles, which is
      often painful and debilitating. As a result, HFS-related symptoms can frequently lead to dose
      reduction and/or discontinuation of otherwise effective anti-cancer treatment. There is no
      treatment for HFS other than dose reduction or stopping treatment. This proposal could
      quickly lead to treatments to prevent and/or treat HFS and help patients avoid debilitating
      side effects while continuing otherwise effective treatments for their cancer.
    

Detailed description: 
      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
      sildenafil.

      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
      sildenafil:

        -  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.
    

Intervention name(s): sildenafil citrate
Intervention type(s): Drug
Intervention description(s): Subjects will be given 2 types of topical creams, one containing 1% sildenafil and one containing placebo control. Subjects will be randomized to apply sildenafil cream to either the right or left hand/foot; placebo cream will be applied to the opposite hand/foot. The cream will be supplied to subjects with proper labeling to indicate right and left application assignment. Cream will be applied to each affected hand/foot two times per day.
Other intervention name(s): Viagra
Intervention MeSH terms: Sildenafil Citrate
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Hand foot syndrome; Palmar Plantar Erythrodysesthesia; chemotherapy; Sunitinib; Capecitebine; Sildenafil