Topical Sildenafil as Pre-Treatment for Hand-Foot Skin Reaction
Topical Sildenafil as Pre-Treatment for Hand-Foot Skin Reaction
Skin toxicities are a major complication to cancer therapies. They can be painful and limit
 the amount of drug that can be received by cancer patients, preventing the patients from
 receiving optimal doses of drug. One such cutaneous toxicity, hand-foot skin reaction (HFSR),
 is caused by next generation targeted agents that are in routine use for the treatment of
 kidney and liver cancer. HFSR is characterized by swelling, redness, and pain of the palms
 and soles, in addition to the development of painful or thickened callus-like plaques with
 fissures in areas of friction and pressure. The investigators have identified a topical
 skin-directed therapy, 1% topical sildenafil cream, that the investigators believe will be
 useful in preventing and ameliorating this painful, skin side effect associated with the
 targeted agents sorafenib and sunitinib. This project proposal aims to conduct an open-label
 pilot study to assess whether pre-medication with this cream can be an effective way of
 preventing or decreasing the severity of hand-foot skin reaction, improving their quality of
 life on therapy and enabling the patients to receive optimal amounts of their anti-cancer
 drug.
The purpose of this study is to evaluate the effect of topical sildenafil as a pre-treatment
 regimen for HFSR in patients naïve to anti-cancer therapy who will be initiated on treatment
 with sorafenib or sunitinib. The study endpoint will be the onset and calculated incidence of
 any grade of HFSR. Skin toxicity grading per National Cancer Institute - Common Terminology
 Criteria for Adverse Events (NCI-CTCAE) v4.03 will be performed by the investigator at each
 visit (every 2 weeks) until the end of the study (12 weeks total).

 This study aims to:

 1. Determine whether HFSR can be prevented with topical sildenafil as pre-treatment.

 2. Determine whether topical sildenafil can reduce the incidence of HFSR in patients
 treated with sorafenib or sunitinib.

 3. Determine whether topical sildenafil can delay the onset of HFSR.

 4. Determine whether topical sildenafil can reduce the severity of skin lesions if HFSR
 does occur.

 Patient Eligibility:

 The target population for this study is patients with clinically-diagnosed cancer who will be
 treated with sorafenib or sunitinib. A total of 20 subjects will be needed for this trial.
 There is no placebo group for this study. Subjects must meet all of the inclusion criteria
 and none of the exclusion criteria to be registered to the study.

 Data Collection:

 Patients will be instructed to apply the treatment cream to both hands and both feet twice a
 day for 12 weeks. After the initial visit to enroll and obtain consent, patient assessment
 will occur in clinic every 2 weeks. At each clinic visit, a skin toxicity grading per
 NCI-CTCAE v4.03 will be performed, any visual skin changes will be documented with
 photography, treatment cream will be refilled, and patient medication diaries will be
 reviewed. A follow up visit will occur within 30 days of the last study treatment. In
 addition, the investigators will collect information to ensure compliance with drug therapy
 (in the form of a subject medication diary).
Inclusion Criteria:

 -  Patients with a clinical diagnosis of cancer that are within ± 3 days of initiating
 treatment with sorafenib or sunitinib. Patients treated with a combination regimen
 that includes sorafenib or sunitinib are eligible.

 -  Patients must be age ≥ 18 years.

 -  Patients must exhibit an ECOG performance status of 0 to 2.

 -  Females of child-bearing potential (FOCBP) and males must agree to use adequate
 contraception (e.g., hormonal contraceptives such as birth control pills, patch,
 intrauterine device; barrier contraception such as male/female condoms, diaphragm;
 male partner with vasectomy; abstinence) prior to study entry, for the duration of
 study participation, and for 30 days following completion of therapy. Should a female
 patient become pregnant or suspect she is pregnant while participating in this study,
 she should inform her treating physician immediately. NOTE: A FOCBP is any woman
 (regardless of sexual orientation, having undergone a tubal ligation, or remaining
 celibate by choice) who meets the following criteria: has not undergone a hysterectomy
 or bilateral oophorectomy or has had menses at any time in the preceding 12
 consecutive months (and therefore has not been naturally postmenopausal for > 12
 months).

 -  FOCBP must have a negative urine or serum pregnancy test within 7 days prior to
 registration on study.

 -  Patients must have the ability to understand and the willingness to sign a written
 informed consent prior to registration in the study.

 Exclusion Criteria:

 -  Patients with a prior diagnosis of hand-foot skin reaction are not eligible.

 -  Patients who have had other chemotherapy or radiotherapy within 4 weeks prior to
 entering the study or those who have not recovered from adverse events due to agents
 administered more than 4 weeks earlier are not eligible.

 -  Patients who have a history of allergic reactions attributed to compounds of similar
 chemical or biologic composition to sildenafil or phosphodiesterase-5 (PDE5)
 inhibitors such as vardenafil (Levitra) and tadalafil (Cialis) are not eligible.

 -  Patients may not be receiving any other investigational agents. Note: it is acceptable
 to be on combination therapy including either sorafenib and/or sunitinib.

 -  Patients must not be using topical steroids (e.g., hydrocortisone). Topical
 over-the-counter antibiotics (e.g., Neosporin) and skin protectants (e.g., Vaseline,
 Aquaphor) for local skin fissures on hands and feet are allowed. Patients are allowed
 to use topical medications on other body parts, besides the hands and feet, but must
 use qtips or gloves for application.

 -  Patients taking nitrates (e.g., nitroglycerin, isosorbide mononitrate, isosorbide
 dinitrate) and/or alpha blockers (e.g., tamsulosin, prazosin, afluzosin, silodosin)
 are not eligible.

 -  Patients taking Viagra must have a 1 day washout period prior to treatment. Note:
 patients must agree to discontinue Viagra while on study treatment.

 -  Female patients who are pregnant or nursing are not eligible.

 -  Patients must not have any condition or situation which, in the investigator's
 opinion, puts the patient at significant risk, could confound the study results, or
 may interfere significantly with the patient's participation in the study.

 -  Patients who are unable to communicate or cooperate with the investigator due to
 language problems, poor mental development, or impaired cerebral function are not
 eligible.