Hand Foot Skin ReactionEarly Phase 1NCT03229512
Topical Sildenafil as Pre-Treatment for Hand-Foot Skin Reaction
A Early Phase 1 study testing Sildenafil in people with Hand Foot Skin Reaction, run by Northwestern University at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hand Foot Skin Reaction
- What is being tested?
- Sildenafil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- 11 Apr 2017to 4 Jun 2020
- Phase
- Early 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Department of Dermatology, Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
Northwestern Memorial Hospital
Chicago, Illinois, 60611
About this study
Official title: An Open Label, Pilot Study Evaluating the Effect of 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.
Read the detailed description
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:
- Determine whether HFSR can be prevented with topical sildenafil as pre-treatment.
- Determine whether topical sildenafil can reduce the incidence of HFSR in patients treated with sorafenib or sunitinib.
- Determine whether topical sildenafil can delay the onset of HFSR.
- 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).
- Conditions
- Hand Foot Skin Reaction
- Being tested
- Sildenafil
- Keywords
- Hand Foot Skin Reaction, Sildenafil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Also called Sildenafil citrate, Viagra
Topical 1% Sildenafil Cream
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Topical 1% Sildenafil Cream Receives: Drug: Sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evidence of hand-foot skin reaction
The primary outcome measure is the onset and calculated incidence of any grade of hand-foot skin reaction during the 12-week study period.
Measured: Within 12 weeks of start of study
Secondary outcomes (1)
Adverse events due to 1% sildenafil cream
Safety endpoints will include number, frequency and severity of adverse events noted by significant changes upon physical examination or vital sign measurements.
Measured: Within 12 weeks of start of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2017
- Study start11 Apr 2017
- Primary completion4 Jun 2020
- Study completion4 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hand Foot Skin ReactionStudies of the same condition, open and under way.
- More trials run by Northwestern 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
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Nam Choi, MD, Northwestern University
- Investigators
- Jennifer N Choi, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03229512
- Sponsor's protocol ID
- JNC052716
- Status last verified
- Oct 2021
- First submitted
- 21 Jul 2017
- Last updated
- 1 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Choi JN. Chemotherapy-induced iatrogenic injury of skin: new drugs and new concepts. Clin Dermatol. 2011 Nov-Dec;29(6):587-601. doi: 10.1016/j.clindermatol.2011.08.032.
PubMed 22014981Lacouture ME, Wu S, Robert C, Atkins MB, Kong HH, Guitart J, Garbe C, Hauschild A, Puzanov I, Alexandrescu DT, Anderson RT, Wood L, Dutcher JP. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist. 2008 Sep;13(9):1001-11. doi: 10.1634/theoncologist.2008-0131. Epub 2008 Sep 8.
PubMed 18779536Meadows KL, Rushing C, Honeycutt W, Latta K, Howard L, Arrowood CA, Niedzwiecki D, Hurwitz HI. Treatment of palmar-plantar erythrodysesthesia (PPE) with topical sildenafil: a pilot study. Support Care Cancer. 2015 May;23(5):1311-9. doi: 10.1007/s00520-014-2465-z. Epub 2014 Oct 24.
PubMed 25341548
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Pilot Study Evaluating the Effect of Topical Sildenafil as Pre-Treatment for Hand-Foot Skin Reaction
- ClinicalTrials.gov ID
- NCT03229512
- Acronym / sponsor ID
- JNC052716
- Conditions
- Hand Foot Skin Reaction
- Keywords
- Hand Foot Skin Reaction, Sildenafil
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- 11 Apr 2017 (actual)
- Primary completion
- 4 Jun 2020 (actual)
- Study completion
- 4 Jun 2020 (actual)
- First posted
- 25 Jul 2017 (actual)
- 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.
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.
Detailed description
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:
- Determine whether HFSR can be prevented with topical sildenafil as pre-treatment.
- Determine whether topical sildenafil can reduce the incidence of HFSR in patients treated with sorafenib or sunitinib.
- Determine whether topical sildenafil can delay the onset of HFSR.
- 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).
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: SildenafilTopical 1% Sildenafil Cream |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
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 |
|---|---|---|
| SildenafilAlso: Sildenafil citrate, ViagraTopical 1% Sildenafil Cream | Drug | Intervention |
Primary outcome
Evidence of hand-foot skin reaction
Time frame: Within 12 weeks of start of study
The primary outcome measure is the onset and calculated incidence of any grade of hand-foot skin reaction during the 12-week study period.
1 secondary outcome
Adverse events due to 1% sildenafil cream
Time frame: Within 12 weeks of start of study
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 1 Nov 2021.
- Background: PubMed 22014981Choi JN. Chemotherapy-induced iatrogenic injury of skin: new drugs and new concepts. Clin Dermatol. 2011 Nov-Dec;29(6):587-601. doi: 10.1016/j.clindermatol.2011.08.032.
- Background: PubMed 18779536Lacouture ME, Wu S, Robert C, Atkins MB, Kong HH, Guitart J, Garbe C, Hauschild A, Puzanov I, Alexandrescu DT, Anderson RT, Wood L, Dutcher JP. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist. 2008 Sep;13(9):1001-11. doi: 10.1634/theoncologist.2008-0131. Epub 2008 Sep 8.
- Background: PubMed 25341548Meadows KL, Rushing C, Honeycutt W, Latta K, Howard L, Arrowood CA, Niedzwiecki D, Hurwitz HI. Treatment of palmar-plantar erythrodysesthesia (PPE) with topical sildenafil: a pilot study. Support Care Cancer. 2015 May;23(5):1311-9. doi: 10.1007/s00520-014-2465-z. Epub 2014 Oct 24.
- Individual participant dataSharing planned: No
Related trials for Hand Foot Skin Reaction
Recruiting
Photobiomodulation Therapy in the Management of Hand-foot Syndrome and Hand-foot Skin Reaction
Hand-foot Syndrome, Hand-foot Skin Reaction
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.
Jennifer N Choi, MD principal investigator
Northwestern University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Sildenafil in people with Hand Foot Skin Reaction, run by Northwestern University at 2 sites 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 6 inclusion and 10 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 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Evidence of hand-foot skin reaction (time frame: Within 12 weeks of start of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03229512, which also lists 3 linked publications.
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 1 Nov 2021.