<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03229512</url>
  </required_header>
  <id_info>
    <org_study_id>JNC052716</org_study_id>
    <nct_id>NCT03229512</nct_id>
  </id_info>
  <brief_title>Topical Sildenafil as Pre-Treatment for Hand-Foot Skin Reaction</brief_title>
  <official_title>An Open Label, Pilot Study Evaluating the Effect of Topical Sildenafil as Pre-Treatment for Hand-Foot Skin Reaction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Northwestern University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Skin toxicities are a major complication to cancer therapies. They can be painful and limit&#xD;
      the amount of drug that can be received by cancer patients, preventing the patients from&#xD;
      receiving optimal doses of drug. One such cutaneous toxicity, hand-foot skin reaction (HFSR),&#xD;
      is caused by next generation targeted agents that are in routine use for the treatment of&#xD;
      kidney and liver cancer. HFSR is characterized by swelling, redness, and pain of the palms&#xD;
      and soles, in addition to the development of painful or thickened callus-like plaques with&#xD;
      fissures in areas of friction and pressure. The investigators have identified a topical&#xD;
      skin-directed therapy, 1% topical sildenafil cream, that the investigators believe will be&#xD;
      useful in preventing and ameliorating this painful, skin side effect associated with the&#xD;
      targeted agents sorafenib and sunitinib. This project proposal aims to conduct an open-label&#xD;
      pilot study to assess whether pre-medication with this cream can be an effective way of&#xD;
      preventing or decreasing the severity of hand-foot skin reaction, improving their quality of&#xD;
      life on therapy and enabling the patients to receive optimal amounts of their anti-cancer&#xD;
      drug.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to evaluate the effect of topical sildenafil as a pre-treatment&#xD;
      regimen for HFSR in patients naïve to anti-cancer therapy who will be initiated on treatment&#xD;
      with sorafenib or sunitinib. The study endpoint will be the onset and calculated incidence of&#xD;
      any grade of HFSR. Skin toxicity grading per National Cancer Institute - Common Terminology&#xD;
      Criteria for Adverse Events (NCI-CTCAE) v4.03 will be performed by the investigator at each&#xD;
      visit (every 2 weeks) until the end of the study (12 weeks total).&#xD;
&#xD;
      This study aims to:&#xD;
&#xD;
        1. Determine whether HFSR can be prevented with topical sildenafil as pre-treatment.&#xD;
&#xD;
        2. Determine whether topical sildenafil can reduce the incidence of HFSR in patients&#xD;
           treated with sorafenib or sunitinib.&#xD;
&#xD;
        3. Determine whether topical sildenafil can delay the onset of HFSR.&#xD;
&#xD;
        4. Determine whether topical sildenafil can reduce the severity of skin lesions if HFSR&#xD;
           does occur.&#xD;
&#xD;
      Patient Eligibility:&#xD;
&#xD;
      The target population for this study is patients with clinically-diagnosed cancer who will be&#xD;
      treated with sorafenib or sunitinib. A total of 20 subjects will be needed for this trial.&#xD;
      There is no placebo group for this study. Subjects must meet all of the inclusion criteria&#xD;
      and none of the exclusion criteria to be registered to the study.&#xD;
&#xD;
      Data Collection:&#xD;
&#xD;
      Patients will be instructed to apply the treatment cream to both hands and both feet twice a&#xD;
      day for 12 weeks. After the initial visit to enroll and obtain consent, patient assessment&#xD;
      will occur in clinic every 2 weeks. At each clinic visit, a skin toxicity grading per&#xD;
      NCI-CTCAE v4.03 will be performed, any visual skin changes will be documented with&#xD;
      photography, treatment cream will be refilled, and patient medication diaries will be&#xD;
      reviewed. A follow up visit will occur within 30 days of the last study treatment. In&#xD;
      addition, the investigators will collect information to ensure compliance with drug therapy&#xD;
      (in the form of a subject medication diary).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 11, 2017</start_date>
  <completion_date type="Actual">June 4, 2020</completion_date>
  <primary_completion_date type="Actual">June 4, 2020</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evidence of hand-foot skin reaction</measure>
    <time_frame>Within 12 weeks of start of study</time_frame>
    <description>The primary outcome measure is the onset and calculated incidence of any grade of hand-foot skin reaction during the 12-week study period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events due to 1% sildenafil cream</measure>
    <time_frame>Within 12 weeks of start of study</time_frame>
    <description>Safety endpoints will include number, frequency and severity of adverse events noted by significant changes upon physical examination or vital sign measurements.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Hand Foot Skin Reaction</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Topical 1% Sildenafil Cream</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sildenafil</intervention_name>
    <description>Topical 1% Sildenafil Cream</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Sildenafil citrate</other_name>
    <other_name>Viagra</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a clinical diagnosis of cancer that are within ± 3 days of initiating&#xD;
             treatment with sorafenib or sunitinib. Patients treated with a combination regimen&#xD;
             that includes sorafenib or sunitinib are eligible.&#xD;
&#xD;
          -  Patients must be age ≥ 18 years.&#xD;
&#xD;
          -  Patients must exhibit an ECOG performance status of 0 to 2.&#xD;
&#xD;
          -  Females of child-bearing potential (FOCBP) and males must agree to use adequate&#xD;
             contraception (e.g., hormonal contraceptives such as birth control pills, patch,&#xD;
             intrauterine device; barrier contraception such as male/female condoms, diaphragm;&#xD;
             male partner with vasectomy; abstinence) prior to study entry, for the duration of&#xD;
             study participation, and for 30 days following completion of therapy. Should a female&#xD;
             patient become pregnant or suspect she is pregnant while participating in this study,&#xD;
             she should inform her treating physician immediately. NOTE: A FOCBP is any woman&#xD;
             (regardless of sexual orientation, having undergone a tubal ligation, or remaining&#xD;
             celibate by choice) who meets the following criteria: has not undergone a hysterectomy&#xD;
             or bilateral oophorectomy or has had menses at any time in the preceding 12&#xD;
             consecutive months (and therefore has not been naturally postmenopausal for &gt; 12&#xD;
             months).&#xD;
&#xD;
          -  FOCBP must have a negative urine or serum pregnancy test within 7 days prior to&#xD;
             registration on study.&#xD;
&#xD;
          -  Patients must have the ability to understand and the willingness to sign a written&#xD;
             informed consent prior to registration in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a prior diagnosis of hand-foot skin reaction are not eligible.&#xD;
&#xD;
          -  Patients who have had other chemotherapy or radiotherapy within 4 weeks prior to&#xD;
             entering the study or those who have not recovered from adverse events due to agents&#xD;
             administered more than 4 weeks earlier are not eligible.&#xD;
&#xD;
          -  Patients who have a history of allergic reactions attributed to compounds of similar&#xD;
             chemical or biologic composition to sildenafil or phosphodiesterase-5 (PDE5)&#xD;
             inhibitors such as vardenafil (Levitra) and tadalafil (Cialis) are not eligible.&#xD;
&#xD;
          -  Patients may not be receiving any other investigational agents. Note: it is acceptable&#xD;
             to be on combination therapy including either sorafenib and/or sunitinib.&#xD;
&#xD;
          -  Patients must not be using topical steroids (e.g., hydrocortisone). Topical&#xD;
             over-the-counter antibiotics (e.g., Neosporin) and skin protectants (e.g., Vaseline,&#xD;
             Aquaphor) for local skin fissures on hands and feet are allowed. Patients are allowed&#xD;
             to use topical medications on other body parts, besides the hands and feet, but must&#xD;
             use qtips or gloves for application.&#xD;
&#xD;
          -  Patients taking nitrates (e.g., nitroglycerin, isosorbide mononitrate, isosorbide&#xD;
             dinitrate) and/or alpha blockers (e.g., tamsulosin, prazosin, afluzosin, silodosin)&#xD;
             are not eligible.&#xD;
&#xD;
          -  Patients taking Viagra must have a 1 day washout period prior to treatment. Note:&#xD;
             patients must agree to discontinue Viagra while on study treatment.&#xD;
&#xD;
          -  Female patients who are pregnant or nursing are not eligible.&#xD;
&#xD;
          -  Patients must not have any condition or situation which, in the investigator's&#xD;
             opinion, puts the patient at significant risk, could confound the study results, or&#xD;
             may interfere significantly with the patient's participation in the study.&#xD;
&#xD;
          -  Patients who are unable to communicate or cooperate with the investigator due to&#xD;
             language problems, poor mental development, or impaired cerebral function are not&#xD;
             eligible.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jennifer N Choi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Dermatology, Northwestern University Feinberg School of Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Memorial Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>22014981</PMID>
  </reference>
  <reference>
    <citation>Lacouture 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.</citation>
    <PMID>18779536</PMID>
  </reference>
  <reference>
    <citation>Meadows 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.</citation>
    <PMID>25341548</PMID>
  </reference>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>July 21, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>October 29, 2021</last_update_submitted>
  <last_update_submitted_qc>October 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Northwestern University</investigator_affiliation>
    <investigator_full_name>Jennifer Nam Choi, MD</investigator_full_name>
    <investigator_title>Chief of Division of Oncodermatology</investigator_title>
  </responsible_party>
  <keyword>Hand Foot Skin Reaction</keyword>
  <keyword>Sildenafil</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sildenafil Citrate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03229512
org study id: JNC052716
nct id: NCT03229512
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Evidence of hand-foot skin reaction
time frame: Within 12 weeks of start of study
description: The primary outcome measure is the onset and calculated incidence of any grade of hand-foot skin reaction during the 12-week study period.
measure: Adverse events due to 1% sildenafil cream
time frame: Within 12 weeks of start of study
description: Safety endpoints will include number, frequency and severity of adverse events noted by significant changes upon physical examination or vital sign measurements.
arm group label: Intervention
arm group type: Experimental
description: Topical 1% Sildenafil Cream
intervention type: Drug
intervention name: Sildenafil
description: Topical 1% Sildenafil Cream
arm group label: Intervention
other name: Sildenafil citrate
other name: Viagra
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer N Choi, MD
role: Principal Investigator
affiliation: Northwestern University
facility: 
facility: 
country: United States
citation: 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.
PMID: 22014981
citation: Lacouture 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.
PMID: 18779536
citation: Meadows 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.
PMID: 25341548
responsible party type: Principal Investigator
investigator affiliation: Northwestern University
investigator full name: Jennifer Nam Choi, MD
investigator title: Chief of Division of Oncodermatology
mesh term: Sildenafil Citrate
sharing ipd: No