<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/NCT02993159</url>
  </required_header>
  <id_info>
    <org_study_id>NCI 2015-06-04</org_study_id>
    <secondary_id>P30CA060553</secondary_id>
    <secondary_id>NCI-2016-01911</secondary_id>
    <secondary_id>N01-CN-2012-00035</secondary_id>
    <secondary_id>NCI 2015-06-04</secondary_id>
    <secondary_id>NWU2015-06-04</secondary_id>
    <secondary_id>N01CN00035</secondary_id>
    <nct_id>NCT02993159</nct_id>
  </id_info>
  <brief_title>Testing an Active Form of Tamoxifen (4-hydroxytamoxifen) Delivered Through the Breast Skin to Control Ductal Carcinoma in Situ (DCIS) of the Breast</brief_title>
  <official_title>Phase IIB Pre-Surgical Trial of Oral Tamoxifen Versus Transdermal 4-hydroxytamoxifen in Women With DCIS of the Breast</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>BHR Pharma, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </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>
      This randomized phase IIB trial studies how well tamoxifen or afimoxifene works in treating&#xD;
      patients with estrogen receptor positive breast cancer. Estrogen can cause the growth of&#xD;
      breast cancer cells. Hormone therapy using tamoxifen citrate or afimoxifene may fight breast&#xD;
      cancer by blocking the use of estrogen by the tumor cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To demonstrate that 2 mg once daily per breast of 4-hydroxytamoxifen (4-OHT) topical gel&#xD;
      results in a reduction in the Ki-67 labeling index of ductal breast carcinoma in situ (DCIS)&#xD;
      lesions that is not inferior to that seen with 20 mg daily oral tamoxifen citrate (TAM) for&#xD;
      4-10 weeks, when comparing the base-line diagnostic core biopsy to the therapeutic surgical&#xD;
      excision sample.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To compare post-therapy changes in the oncotype DCIS-score between arms (this is a&#xD;
      validated reverse transcriptase-polymerase chain reaction [RT-PCR] assay for Ki67, STK15,&#xD;
      survivin, cyclin B1, MYBL2, PR, GSTM1).&#xD;
&#xD;
      II. To compare between-group post-therapy changes in immunohistochemistry (IHC) markers:&#xD;
      CD-68 macrophage marker as a surrogate for response to therapy, p16 and COX-2.&#xD;
&#xD;
      III. To compare post-therapy changes in breast density, quantitative estimate, between arms.&#xD;
&#xD;
      IV. To compare post-therapy breast tissue and plasma levels of TAM and its metabolites&#xD;
      (N-desmethyl tamoxifen [NDT], [E] and [Z] isomers of 4-hydroxytamoxifen [4-OHT],&#xD;
      N-desmethyl-4-hydroxytamoxifen [endoxifen]).&#xD;
&#xD;
      V. To compare post-therapy breast tissue and plasma levels of estradiol and progesterone&#xD;
      between arms (optional).&#xD;
&#xD;
      VI. To compare the post-therapy fraction of participants demonstrating &quot;no residual DCIS&quot;.&#xD;
&#xD;
      VII. To compare post-therapy changes in plasma proteins involved in coagulation: factors VIII&#xD;
      and IX, von Willebrand factor, total protein S between arms.&#xD;
&#xD;
      VIII. To compare post-therapy changes in plasma markers of systemic estrogenic effect (IGF-1,&#xD;
      SHBG).&#xD;
&#xD;
      IX. To compare post-therapy changes in symptoms as captured in the breast cancer prevention&#xD;
      trial (BCPT) Eight Symptom Scale (BESS) questionnaire and skin reactions to 4-OHT gel.&#xD;
&#xD;
      OUTLINE: Patients are randomized into 1 of 2 arms.&#xD;
&#xD;
      ARM I: Patients apply afimoxifene gel to both breasts and receive placebo orally (PO) daily&#xD;
      for 4-10 weeks in the absence of disease progression or unexpected toxicity.&#xD;
&#xD;
      ARM II: Patients apply placebo gel to both breasts and receive tamoxifen citrate orally PO&#xD;
      daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 1-2 weeks and 1 month after&#xD;
      surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 31, 2017</start_date>
  <completion_date type="Anticipated">July 15, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 15, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ki67 labeling assessed by standard immunohistochemistry</measure>
    <time_frame>Up to 1 month after surgery</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>CD68, p16, and COX2 assessed by IHC</measure>
    <time_frame>Up to 1 month after surgery</time_frame>
    <description>Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estradiol and progesterone levels in breast tissue and plasma assessed by liquid chromatography/tandem mass spectrometry</measure>
    <time_frame>Up to 1 month after surgery</time_frame>
    <description>Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of subjects with &quot;no residual DCIS&quot; in surgical sample assessed by core needle biopsy</measure>
    <time_frame>Up to 1 month after surgery</time_frame>
    <description>Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oncotype DCIS-score assessed by RT-PCR</measure>
    <time_frame>Up to 1 month after surgery</time_frame>
    <description>Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathologic complete response defined as absence of residual DCIS or residual DCIS responded completely to therapy</measure>
    <time_frame>Up to 1 month after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma markers of systemic estrogenic effect (IGF-1, SHBG)</measure>
    <time_frame>Up to 1 month after surgery</time_frame>
    <description>Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma proteins involved in coagulation (factors VIII and IX, von Willebrand factor, and total protein S)</measure>
    <time_frame>Up to 1 month after surgery</time_frame>
    <description>Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptoms assessed by BESS questionnaire</measure>
    <time_frame>Up to 1 month after surgery</time_frame>
    <description>Will evaluate hot flashes, vaginal discharge/dryness, skin reactions to afimoxifene gel. Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TAM and its metabolites levels in breast tissue and plasma</measure>
    <time_frame>Up to 1 month after surgery</time_frame>
    <description>Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Ductal Breast Carcinoma In Situ</condition>
  <condition>Estrogen Receptor Positive</condition>
  <arm_group>
    <arm_group_label>Arm I (afimoxifene, placebo)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients apply afimoxifene gel to both breasts and receive placebo PO daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (placebo, tamoxifen citrate)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients apply placebo gel to both breasts and receive tamoxifen citrate orally PO daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Afimoxifene</intervention_name>
    <description>Applied to the breast</description>
    <arm_group_label>Arm I (afimoxifene, placebo)</arm_group_label>
    <other_name>4-Hydroxy-Tamoxifen</other_name>
    <other_name>4-Hydroxytamoxifen</other_name>
    <other_name>4-OHT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (afimoxifene, placebo)</arm_group_label>
    <arm_group_label>Arm II (placebo, tamoxifen citrate)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (afimoxifene, placebo)</arm_group_label>
    <other_name>placebo therapy</other_name>
    <other_name>PLCB</other_name>
    <other_name>sham therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Applied to the breast</description>
    <arm_group_label>Arm II (placebo, tamoxifen citrate)</arm_group_label>
    <other_name>placebo therapy</other_name>
    <other_name>PLCB</other_name>
    <other_name>sham therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tamoxifen Citrate</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm II (placebo, tamoxifen citrate)</arm_group_label>
    <other_name>Apo-Tamox</other_name>
    <other_name>Clonoxifen</other_name>
    <other_name>Dignotamoxi</other_name>
    <other_name>Ebefen</other_name>
    <other_name>Emblon</other_name>
    <other_name>Estroxyn</other_name>
    <other_name>Fentamox</other_name>
    <other_name>Gen-Tamoxifen</other_name>
    <other_name>Genox</other_name>
    <other_name>ICI 46,474</other_name>
    <other_name>ICI-46474</other_name>
    <other_name>Jenoxifen</other_name>
    <other_name>Kessar</other_name>
    <other_name>Ledertam</other_name>
    <other_name>Lesporene</other_name>
    <other_name>Nolgen</other_name>
    <other_name>Noltam</other_name>
    <other_name>Nolvadex</other_name>
    <other_name>Nolvadex-D</other_name>
    <other_name>Nourytam</other_name>
    <other_name>Novo-Tamoxifen</other_name>
    <other_name>Novofen</other_name>
    <other_name>Noxitem</other_name>
    <other_name>Oestrifen</other_name>
    <other_name>Oncotam</other_name>
    <other_name>PMS-Tamoxifen</other_name>
    <other_name>Soltamox</other_name>
    <other_name>TAM</other_name>
    <other_name>Tamax</other_name>
    <other_name>Tamaxin</other_name>
    <other_name>Tamifen</other_name>
    <other_name>Tamizam</other_name>
    <other_name>Tamofen</other_name>
    <other_name>Tamoxasta</other_name>
    <other_name>Tamoxifeni Citras</other_name>
    <other_name>Zemide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Screen-detected, estrogen receptor (ER) positive DCIS of the breast proven on core&#xD;
             needle biopsy, defined as 10% positive cells; the presence of a focus suspicious for&#xD;
             microinvasion will be allowed; the size of the DCIS in the core biopsy sample must&#xD;
             total 5 mm (multiple cores can be summed) and must be estimated on the deepest step&#xD;
             section (if step sections are taken)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 1 (Karnofsky &gt;= 70%)&#xD;
&#xD;
          -  Participants must have acceptable organ and marrow function as defined below:&#xD;
&#xD;
        Baseline lab parameters are not standard of care for initiation of tamoxifen therapy; a&#xD;
        minimal panel will therefore be appropriate.&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/microliter&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/microliter&#xD;
&#xD;
          -  Platelets &gt;= 100,000/microliter&#xD;
&#xD;
          -  Total bilirubin within &quot;≤1.5 x institutional upper limit of normal (ULN)institutional&#xD;
             limits&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 1.5 x institutional upper limit of normal (ULN)&#xD;
&#xD;
          -  Creatinine within &quot;≤1.5 x institutional upper limit of normal (ULN) institutional&#xD;
             limits&#xD;
&#xD;
          -  Women of childbearing potential and their male partners must agree to use TWO&#xD;
             effective forms of birth control (abstinence is not an allowed method) prior to study&#xD;
             entry and for the duration of study participation, and for two months following the&#xD;
             last dose of study medications; effective birth control methods are: copper IUD&#xD;
             [intrauterine device], diaphragm/cervical cap/shield, spermicide, contraceptive&#xD;
             sponge, condoms; women of childbearing potential must have a negative urine pregnancy&#xD;
             test within seven days before starting study medications; should a woman become&#xD;
             pregnant or suspect she is pregnant while participating in this study, she should&#xD;
             inform her study physician immediately&#xD;
&#xD;
          -  Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e.&#xD;
             tanning beds) for the duration of the study&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  DCIS presentation as a palpable mass&#xD;
&#xD;
          -  Exogenous sex steroid use within 4 weeks prior to core needle biopsy&#xD;
&#xD;
          -  Prior ipsilateral breast cancer radiotherapy will be excluded; prior contralateral&#xD;
             breast cancer therapy within 2 years will also be excluded&#xD;
&#xD;
          -  Skin lesions on the breast that disrupt the stratum corneum (eg eczema, ulceration)&#xD;
&#xD;
          -  History of endometrial neoplasia&#xD;
&#xD;
          -  History of thromboembolic disease (history of varicose veins and superficial phlebitis&#xD;
             is allowed)&#xD;
&#xD;
          -  Current smokers&#xD;
&#xD;
          -  Current users of potent inhibitors of tamoxifen metabolism must be able to discontinue&#xD;
             their use and switch to an alternative medication for the duration of participation,&#xD;
             under the advice of their physician; if the physician feels that an alternative&#xD;
             medication is not appropriate for the subject and the current medication is medically&#xD;
             necessary, the subject will not be eligible; the drugs are listed below; many of these&#xD;
             are not in clinical use at the moment; bupropion, celecoxib, chlorpheniramine,&#xD;
             chlorpromazine, cimetidine, citalopram, clemastine, clomipramine, clozapine, cocaine,&#xD;
             delavirdine, desipramine, diphenhydramine, doxepin, duloxetine, escitalopram,&#xD;
             fluoxetine, haloperidol, halofantrine, hydroxyzine, imipramine, isoniazid,&#xD;
             ketoconazole, methadone, methimazole, mibefradil, miconazole, nicardipine, paroxetine,&#xD;
             pergolide, perphenazine, pioglitazone, pyrimethamine, quinidine, quinine, ranitidine,&#xD;
             ritonavir, ropinirole, sertraline, terbinafine, thioridazine, ticlopidine,&#xD;
             tranylcypromine, trazodone, tripelennamine&#xD;
&#xD;
          -  Prior use of SERMS or AIs including tamoxifen, raloxifene, anastrozole, letrozole, or&#xD;
             exemestane for prevention or therapy within 5 years&#xD;
&#xD;
          -  Participants may not be receiving any other investigational agents within 30 days of&#xD;
             enrollment or during this study&#xD;
&#xD;
          -  History of allergic reactions attributed to tamoxifen or compounds of similar chemical&#xD;
             or biologic composition&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  Pregnant women are excluded from this study; breastfeeding should be discontinued by&#xD;
             nursing mothers who agree to participate in the study&#xD;
&#xD;
          -  Men are excluded from this study since DCIS of the breast is exceedingly rare in men,&#xD;
             and there are no data regarding skin penetration of 4-OHT though male chest wall skin&#xD;
             (which is thicker and hairier than female chest wall skin)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Seema Khan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Principle Investigator</last_name>
    <phone>312-503-4236</phone>
    <email>skhan@nm.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Seema A. Khan, MD</last_name>
      <phone>312-503-4236</phone>
      <email>skhan@nm.org</email>
    </contact>
    <investigator>
      <last_name>Seema A. Khan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Saint Elizabeth Medical Center South</name>
      <address>
        <city>Edgewood</city>
        <state>Kentucky</state>
        <zip>41017</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joseph M. Guenther, MD</last_name>
      <phone>859-344-1600</phone>
      <email>Joseph.Guenther@stelizabeth.com</email>
    </contact>
    <investigator>
      <last_name>Joseph M. Guenther, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amy C. Degnim, MD</last_name>
      <phone>507-284-4499</phone>
      <email>degnim.amy@mayo.edu</email>
    </contact>
    <investigator>
      <last_name>Amy C. Degnim, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan-Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melissa L. Pilewskie, MD</last_name>
      <phone>646-888-4590</phone>
      <email>pilewskm@mskcc.org</email>
    </contact>
    <investigator>
      <last_name>Melissa L. Pilewskie, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eun-Sil (Shelley) Hwang, MD</last_name>
      <phone>919-684-6849</phone>
      <email>shelly.hwang@duke.edu</email>
    </contact>
    <investigator>
      <last_name>Eun-Sil (Shelley) Hwang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stephen R. Grobmyer, MD</last_name>
      <phone>216-636-2843</phone>
      <email>TaussigResearch@ccf.org</email>
    </contact>
    <investigator>
      <last_name>Stephen R. Grobmyer, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 14, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>December 17, 2020</last_update_submitted>
  <last_update_submitted_qc>December 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Carcinoma in Situ</mesh_term>
    <mesh_term>Carcinoma, Ductal, Breast</mesh_term>
    <mesh_term>Breast Carcinoma In Situ</mesh_term>
    <mesh_term>Carcinoma, Intraductal, Noninfiltrating</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tamoxifen</mesh_term>
    <mesh_term>Afimoxifene</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>October 19, 2022</submitted>
    <returned>November 10, 2022</returned>
  </pending_results>
  <!-- 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/NCT02993159
org study id: NCI 2015-06-04
secondary id: P30CA060553
secondary id: NCI-2016-01911
secondary id: N01-CN-2012-00035
secondary id: NCI 2015-06-04
secondary id: NWU2015-06-04
secondary id: N01CN00035
nct id: NCT02993159
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This randomized phase IIB trial studies how well tamoxifen or afimoxifene works in treating
      patients with estrogen receptor positive breast cancer. Estrogen can cause the growth of
      breast cancer cells. Hormone therapy using tamoxifen citrate or afimoxifene may fight breast
      cancer by blocking the use of estrogen by the tumor cells.
PRIMARY OBJECTIVES:

      I. To demonstrate that 2 mg once daily per breast of 4-hydroxytamoxifen (4-OHT) topical gel
      results in a reduction in the Ki-67 labeling index of ductal breast carcinoma in situ (DCIS)
      lesions that is not inferior to that seen with 20 mg daily oral tamoxifen citrate (TAM) for
      4-10 weeks, when comparing the base-line diagnostic core biopsy to the therapeutic surgical
      excision sample.

      SECONDARY OBJECTIVES:

      I. To compare post-therapy changes in the oncotype DCIS-score between arms (this is a
      validated reverse transcriptase-polymerase chain reaction [RT-PCR] assay for Ki67, STK15,
      survivin, cyclin B1, MYBL2, PR, GSTM1).

      II. To compare between-group post-therapy changes in immunohistochemistry (IHC) markers:
      CD-68 macrophage marker as a surrogate for response to therapy, p16 and COX-2.

      III. To compare post-therapy changes in breast density, quantitative estimate, between arms.

      IV. To compare post-therapy breast tissue and plasma levels of TAM and its metabolites
      (N-desmethyl tamoxifen [NDT], [E] and [Z] isomers of 4-hydroxytamoxifen [4-OHT],
      N-desmethyl-4-hydroxytamoxifen [endoxifen]).

      V. To compare post-therapy breast tissue and plasma levels of estradiol and progesterone
      between arms (optional).

      VI. To compare the post-therapy fraction of participants demonstrating "no residual DCIS".

      VII. To compare post-therapy changes in plasma proteins involved in coagulation: factors VIII
      and IX, von Willebrand factor, total protein S between arms.

      VIII. To compare post-therapy changes in plasma markers of systemic estrogenic effect (IGF-1,
      SHBG).

      IX. To compare post-therapy changes in symptoms as captured in the breast cancer prevention
      trial (BCPT) Eight Symptom Scale (BESS) questionnaire and skin reactions to 4-OHT gel.

      OUTLINE: Patients are randomized into 1 of 2 arms.

      ARM I: Patients apply afimoxifene gel to both breasts and receive placebo orally (PO) daily
      for 4-10 weeks in the absence of disease progression or unexpected toxicity.

      ARM II: Patients apply placebo gel to both breasts and receive tamoxifen citrate orally PO
      daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.

      After completion of study treatment, patients are followed up at 1-2 weeks and 1 month after
      surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Ki67 labeling assessed by standard immunohistochemistry
time frame: Up to 1 month after surgery
measure: CD68, p16, and COX2 assessed by IHC
time frame: Up to 1 month after surgery
description: Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
measure: Estradiol and progesterone levels in breast tissue and plasma assessed by liquid chromatography/tandem mass spectrometry
time frame: Up to 1 month after surgery
description: Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
measure: Fraction of subjects with "no residual DCIS" in surgical sample assessed by core needle biopsy
time frame: Up to 1 month after surgery
description: Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
measure: Oncotype DCIS-score assessed by RT-PCR
time frame: Up to 1 month after surgery
description: Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
measure: Pathologic complete response defined as absence of residual DCIS or residual DCIS responded completely to therapy
time frame: Up to 1 month after surgery
measure: Plasma markers of systemic estrogenic effect (IGF-1, SHBG)
time frame: Up to 1 month after surgery
description: Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
measure: Plasma proteins involved in coagulation (factors VIII and IX, von Willebrand factor, and total protein S)
time frame: Up to 1 month after surgery
description: Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
measure: Symptoms assessed by BESS questionnaire
time frame: Up to 1 month after surgery
description: Will evaluate hot flashes, vaginal discharge/dryness, skin reactions to afimoxifene gel. Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
measure: TAM and its metabolites levels in breast tissue and plasma
time frame: Up to 1 month after surgery
description: Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
arm group label: Arm I (afimoxifene, placebo)
arm group type: Experimental
description: Patients apply afimoxifene gel to both breasts and receive placebo PO daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.
arm group label: Arm II (placebo, tamoxifen citrate)
arm group type: Active Comparator
description: Patients apply placebo gel to both breasts and receive tamoxifen citrate orally PO daily for 4-10 weeks in the absence of disease progression or unexpected toxicity.
intervention type: Drug
intervention name: Afimoxifene
description: Applied to the breast
arm group label: Arm I (afimoxifene, placebo)
other name: 4-Hydroxy-Tamoxifen
other name: 4-Hydroxytamoxifen
other name: 4-OHT
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm I (afimoxifene, placebo)
arm group label: Arm II (placebo, tamoxifen citrate)
intervention type: Other
intervention name: Placebo
description: Given PO
arm group label: Arm I (afimoxifene, placebo)
other name: placebo therapy
other name: PLCB
other name: sham therapy
intervention type: Other
intervention name: Placebo
description: Applied to the breast
arm group label: Arm II (placebo, tamoxifen citrate)
other name: placebo therapy
other name: PLCB
other name: sham therapy
intervention type: Drug
intervention name: Tamoxifen Citrate
description: Given PO
arm group label: Arm II (placebo, tamoxifen citrate)
other name: Apo-Tamox
other name: Clonoxifen
other name: Dignotamoxi
other name: Ebefen
other name: Emblon
other name: Estroxyn
other name: Fentamox
other name: Gen-Tamoxifen
other name: Genox
other name: ICI 46,474
other name: ICI-46474
other name: Jenoxifen
other name: Kessar
other name: Ledertam
other name: Lesporene
other name: Nolgen
other name: Noltam
other name: Nolvadex
other name: Nolvadex-D
other name: Nourytam
other name: Novo-Tamoxifen
other name: Novofen
other name: Noxitem
other name: Oestrifen
other name: Oncotam
other name: PMS-Tamoxifen
other name: Soltamox
other name: TAM
other name: Tamax
other name: Tamaxin
other name: Tamifen
other name: Tamizam
other name: Tamofen
other name: Tamoxasta
other name: Tamoxifeni Citras
other name: Zemide
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Seema Khan, MD
role: Principal Investigator
affiliation: Northwestern University
last name: Principle Investigator
phone: 312-503-4236
email: skhan@nm.org
facility: 
status: Recruiting
contact: 
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status: Recruiting
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country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Breast Neoplasms
mesh term: Carcinoma in Situ
mesh term: Carcinoma, Ductal, Breast
mesh term: Breast Carcinoma In Situ
mesh term: Carcinoma, Intraductal, Noninfiltrating
mesh term: Tamoxifen
mesh term: Afimoxifene
submitted: October 19, 2022
returned: November 10, 2022