Back to resultsTreatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil (JADE)
Primary Purpose
Hand Foot Syndrome, Palmar Plantar Erythrodysesthesia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
sildenafil citrate
Sponsored by
About this trial
This is an interventional treatment trial for Hand Foot Syndrome focused on measuring Hand foot syndrome, Palmar Plantar Erythrodysesthesia, chemotherapy, Sunitinib, Capecitebine, Sildenafil
Eligibility Criteria
Inclusion Criteria:
Subjects must meet the following criteria to be eligible for the study:
- Receiving capecitabine or sunitinib as part of routine standard care.
- CTCAE version 4.0, grade 1-3 PPE.
- Adults age ≥ 18
- Karnofsky (KPS) performance status of ≥70%
Adequate organ and marrow function as defined below:
- - ANC > 1000/mL
- - Platelets > 75,000/mL
- - Total bilirubin < 1.5 x UNL
- - AST(SGOT)/ALT(SGPT) < 5 x UNL
- - Creatinine Cr Cl est > 40 mL/min (by Cockcroft-Gault)
- Not pregnant or lactating.
- 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.
- 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:
- Currently participating in a clinical trial.
- History of hypersensitivity or intolerance to sildenafil or other related products tadalafil (Cialis™), vardenafil (Levitra™) or poloxamer vehicle.
- Currently taking oral sildenafil or other related products tadalafil (Cialis™), vardenafil (Levitra™).
- Currently taking other treatment for PPE other than standard emollients.
- Using organic nitrates, either regularly and/or intermittently, in any form.
- History of myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.
- 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.
- Cardiac failure or coronary artery disease causing unstable angina.
- Known retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).
- Concomitant use of strong cytochrome P450 3A4 inducers or inhibitors (Ex: ketoconazole, itraconazole, erythromycin, saquinavir).
- Other acute or chronic inflammatory conditions or infections of the hands or feet that would complicate safety, application of topical creams, or study endpoints.
- 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.
- Pregnant or breast-feeding and/or lactating.
- Inability or unwillingness to comply with protocol.
Sites / Locations
- Duke University Medical Center
Outcomes
Primary Outcome Measures
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)
Assessment of patient reported pain, at rest and when making a fist, using a 1-10 score.
Assessment of patient reported pain, at rest and when making a fist, using a 1-10 score, is collected on a diary card that subjects fill out twice daily.
Assessment of severity of erythema and desquamation or blistering as measured on 0-4 score from photographs.
Assessment of severity of erythema and desquamation or blistering as measured on 0-4 score from photographs of hands and/or feet taken every two weeks (for subjects in sunitinib arm) or every 3 weeks (for subjects in capecitabine arm).
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01219023
Brief Title
Treatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil
Acronym
JADE
Official Title
Treatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil
Study Type
Interventional
2. Study Status
Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
April 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hand Foot Syndrome, Palmar Plantar Erythrodysesthesia
Keywords
Hand foot syndrome, Palmar Plantar Erythrodysesthesia, chemotherapy, Sunitinib, Capecitebine, Sildenafil
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
sildenafil citrate
Other Intervention Name(s)
Viagra
Intervention Description
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.
Primary Outcome Measure Information:
Title
Grade of hand foot syndrome over time as measured by NCI CTC version 4.0 PPE syndrome criteria
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)
Time Frame
Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)
Title
Assessment of patient reported pain, at rest and when making a fist, using a 1-10 score.
Description
Assessment of patient reported pain, at rest and when making a fist, using a 1-10 score, is collected on a diary card that subjects fill out twice daily.
Time Frame
twice daily
Title
Assessment of severity of erythema and desquamation or blistering as measured on 0-4 score from photographs.
Description
Assessment of severity of erythema and desquamation or blistering as measured on 0-4 score from photographs of hands and/or feet taken every two weeks (for subjects in sunitinib arm) or every 3 weeks (for subjects in capecitabine arm).
Time Frame
Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must meet the following criteria to be eligible for the study:
Receiving capecitabine or sunitinib as part of routine standard care.
CTCAE version 4.0, grade 1-3 PPE.
Adults age ≥ 18
Karnofsky (KPS) performance status of ≥70%
Adequate organ and marrow function as defined below:
- ANC > 1000/mL
- Platelets > 75,000/mL
- Total bilirubin < 1.5 x UNL
- AST(SGOT)/ALT(SGPT) < 5 x UNL
- Creatinine Cr Cl est > 40 mL/min (by Cockcroft-Gault)
Not pregnant or lactating.
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.
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:
Currently participating in a clinical trial.
History of hypersensitivity or intolerance to sildenafil or other related products tadalafil (Cialis™), vardenafil (Levitra™) or poloxamer vehicle.
Currently taking oral sildenafil or other related products tadalafil (Cialis™), vardenafil (Levitra™).
Currently taking other treatment for PPE other than standard emollients.
Using organic nitrates, either regularly and/or intermittently, in any form.
History of myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.
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.
Cardiac failure or coronary artery disease causing unstable angina.
Known retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).
Concomitant use of strong cytochrome P450 3A4 inducers or inhibitors (Ex: ketoconazole, itraconazole, erythromycin, saquinavir).
Other acute or chronic inflammatory conditions or infections of the hands or feet that would complicate safety, application of topical creams, or study endpoints.
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.
Pregnant or breast-feeding and/or lactating.
Inability or unwillingness to comply with protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Herbert Hurwitz, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
12. IPD Sharing Statement
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Treatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil
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