Treatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil
18 Years
90 Years
Both
Hand Foot Syndrome, Palmar Plantar Erythrodysesthesia
Trial Information
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
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.
Inclusion Criteria:
Subjects must meet the following criteria to be eligible for the study:
1. Receiving capecitabine or sunitinib as part of routine standard care.
2. CTCAE version 4.0, grade 1-3 PPE.
3. Adults age ≥ 18
4. Karnofsky (KPS) performance status of ≥70%
5. Adequate organ and marrow function as defined below:
1. - ANC > 1000/mL
2. - Platelets > 75,000/mL
3. - Total bilirubin < 1.5 x UNL
4. - AST(SGOT)/ALT(SGPT) < 5 x UNL
5. - Creatinine Cr Cl est > 40 mL/min (by Cockcroft-Gault)
6. Not pregnant or lactating.
7. Use of adequate birth control with female partners of male subjects agreeing to use a
medically acceptable form of birth control: (1) surgical sterilization, (2) approved
hormonal contraceptives (such as birth control pills or Depo-Provera), (3) barrier
methods (such as a condom or diaphragm) used with a spermicide, (4) an intrauterine
device (IUD) or (5) post menopausal. Abstinence is not considered acceptable birth
control. Postmenopausal woman must have been amenorrheic for at least 12 months to
be considered of non-childbearing potential.
8. Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
Subjects meeting any of the following criteria are ineligible for study entry:
1. Currently participating in a clinical trial.
2. History of hypersensitivity or intolerance to sildenafil or other related products
tadalafil (Cialis™), vardenafil (Levitra™) or poloxamer vehicle.
3. Currently taking oral sildenafil or other related products tadalafil (Cialis™),
vardenafil (Levitra™).
4. Currently taking other treatment for PPE other than standard emollients.
5. Using organic nitrates, either regularly and/or intermittently, in any form.
6. History of myocardial infarction, stroke, or life-threatening arrhythmia within the
last 6 months.
7. Resting hypotension (BP <90/50 mmHg) or hypertension (BP >170/110 mmHg). Those
subjects on alpha-blocker or anti-hypertensive therapy must be hemodynamically stable
for at least two weeks before day 1 of study drug.
8. Cardiac failure or coronary artery disease causing unstable angina.
9. Known retinitis pigmentosa (a minority of these patients have genetic disorders of
retinal phosphodiesterases).
10. Concomitant use of strong cytochrome P450 3A4 inducers or inhibitors (Ex:
ketoconazole, itraconazole, erythromycin, saquinavir).
11. Other acute or chronic inflammatory conditions or infections of the hands or feet
that would complicate safety, application of topical creams, or study endpoints.
12. History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of an investigational drug or that might affect the
interpretation of the results of the study or render the subject at high risk from
treatment complications.
13. Pregnant or breast-feeding and/or lactating.
14. Inability or unwillingness to comply with protocol.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Outcome Measure:
Grade of hand foot syndrome over time as measured by NCI CTC version 4.0 PPE syndrome criteria
Outcome Description:
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)
Outcome Time Frame:
Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)
Safety Issue:
No
Principal Investigator
Herbert Hurwitz, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Duke University
Authority:
United States: Institutional Review Board
Study ID:
Pro00021480
NCT ID:
NCT01219023
Start Date:
June 2010
Completion Date:
April 2012
Related Keywords:
- Hand Foot Syndrome
- Palmar Plantar Erythrodysesthesia
- Hand foot syndrome
- Palmar Plantar Erythrodysesthesia
- chemotherapy
- Sunitinib
- Capecitebine
- Sildenafil
Name | Location |
|---|---|
| Duke University Medical Center | Durham, North Carolina 27710 |
