Hand Foot SyndromePhase 1JADENCT01219023
Treatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil
A Phase 1 study testing sildenafil citrate in people with Hand Foot Syndrome and Palmar Plantar Erythrodysesthesia, run by Duke University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Hand Foot Syndrome, Palmar Plantar Erythrodysesthesia
- What is being tested?
- sildenafil citrate
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to Apr 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- - 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
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.
Read the 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.
- Being tested
- sildenafil citrate
- Keywords
- Hand foot syndrome, Palmar Plantar Erythrodysesthesia, chemotherapy, Sunitinib, Capecitebine, Sildenafil
- Medical subject headings
- Hand-Foot Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sildenafil citrateDrug
Also called Viagra
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)
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.
Measured: 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).
Measured: Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2010 (estimated)
- Study startJun 2010
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hand Foot SyndromeStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Herbert Hurwitz, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01219023
- Sponsor's protocol ID
- Pro00021480
- Acronym
- JADE
- Status last verified
- Oct 2012
- First submitted
- 8 Oct 2010
- Last updated
- 30 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil
- ClinicalTrials.gov ID
- NCT01219023
- Acronym / sponsor ID
- JADE / Pro00021480
- Keywords
- Hand foot syndrome, Palmar Plantar Erythrodysesthesia, chemotherapy, Sunitinib, Capecitebine, Sildenafil
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- Jun 2010
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 13 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sildenafil citrateAlso: ViagraSubjects 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. | Drug | – |
Primary outcome
Grade of hand foot syndrome over time as measured by NCI CTC version 4.0 PPE syndrome criteria
Time frame: Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)
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.
Time frame: twice daily
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.
Time frame: Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Herbert Hurwitz, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sildenafil citrate in people with Hand Foot Syndrome and Palmar Plantar Erythrodysesthesia, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Grade of hand foot syndrome over time as measured by NCI CTC version 4.0 PPE syndrome criteria (time frame: Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2012.