<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/NCT02238509</url>
  </required_header>
  <id_info>
    <org_study_id>GIM12-TYPHER</org_study_id>
    <secondary_id>2013-005044-29</secondary_id>
    <nct_id>NCT02238509</nct_id>
  </id_info>
  <brief_title>Safety and QoL of Trastuzumab With Lapatinib or Chemiotherapy in MBC and HER2+ Patients Refractory to Anti HER2 Therapies</brief_title>
  <official_title>A Randomised, Multicentre, Open-label Phase II Trial Investigating Activity of Chemotherapy and Lapatinib and Trastuzumab in Patients With HER2-positive Metastatic Breast Cancer (MBC) Refractory to Anti HER2 Therapies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Consorzio Oncotech</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Clinical Research Technology S.r.l.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Consorzio Oncotech</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recent clinical studies have shown that the combination of lapatinib and trastuzumab has&#xD;
      superior antitumor activity compared to either single drug in both neoadjuvant and metastatic&#xD;
      setting and is well tolerated. According to this evidence, the combination of lapatinib and&#xD;
      trastuzumab today offers a valid chemotherapy-free option, primarily for patients with&#xD;
      pre-treated HER2-positive MBC&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The present study is designed to determine the efficacy and safety profile of the combination&#xD;
      of lapatinib and trastuzumab (plus endocrinetherapy in ER-positive breast cancer) versus&#xD;
      trastuzumab and chemotherapy in heavily pretreated patient population with HER2-positive MBC&#xD;
      and to investigate the predictive role of cfDNA for detection of HER2 gene amplification on&#xD;
      patients' outcome. The presence of circulating free DNA (cfDNA) for detection of HER2 gene&#xD;
      amplification was associated with worse prognosis and seems to allow early response&#xD;
      evaluation. However, many aspects of the role of cfDNA detection in patients undergoing&#xD;
      molecular target agents such as trastuzumab or lapatinib are not well described. With the&#xD;
      availability of improved and standardized techniques for cfDNA detection, it should now be&#xD;
      possible to examine several of these important questions within a prospective multicenter&#xD;
      study and a striking potential of cfDNA for detection of HER2 gene amplification might enable&#xD;
      a more individual and optimized antimetastatic therapy inpatients with cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2014</start_date>
  <completion_date type="Anticipated">October 2017</completion_date>
  <primary_completion_date type="Anticipated">October 2017</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical Benefit Rate</measure>
    <time_frame>Clinical Benefit Rate is defined as confirmed complete response plus partial response at any time, plus stable disease up to 24 weeks</time_frame>
    <description>To evaluate clinical benefit rate (CBR) for patients treated with lapatinib and trastuzumab and for patients treated with trastuzumab and chemotherapy. CBR is defined as: confirmed complete response (CR) plus partial response (PR) at any time, plus stable disease (SD) for 24 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months</time_frame>
    <description>Second-line progression-free survival, defined as the time from first dosing to the first documented disease progression or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months</time_frame>
    <description>OS is defined as the time from first dosing in second line to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability</measure>
    <time_frame>Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months</time_frame>
    <description>Safety of second line treatment will be evaluated by the frequency of AEs and SAEs, cardiac events, clinically significant abnormal laboratory tests, vital signs, and ECOG PS. All patients who received at least one dose of study treatment will be included in the safety analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months</time_frame>
    <description>QoL and symptom control will be assessed using the FACT-B questionnaire.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">154</enrollment>
  <condition>Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>lapatinib and trastuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ARM A: Lapatinib and trastuzumab (experimental arm). Patients with hormone receptor (HR) positive breast cancer will also receive endocrine therapy at the physician's discretion (preferred choice with fulvestrant).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>trastuzumab plus chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ARM B: Trastuzumab plus chemotherapy (control arm). Any type of chemotherapy in combination with trastuzumab will be allowed at the physician's discretion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lapatinib</intervention_name>
    <description>ARM A: oral lapatinib 1,000 mg daily in combination with intravenous trastuzumab 6mg/kg q3wks (after the initial 8 mg/kg loading dose).</description>
    <arm_group_label>lapatinib and trastuzumab</arm_group_label>
    <other_name>Tyverb</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <description>ARM A: oral lapatinib 1,000 mg daily in combination with intravenous trastuzumab 6mg/kg q3wks (after the initial 8 mg/kg loading dose).</description>
    <arm_group_label>lapatinib and trastuzumab</arm_group_label>
    <arm_group_label>trastuzumab plus chemotherapy</arm_group_label>
    <other_name>Herceptin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological or cytological confirmed and documented adenocarcinoma of the breast with&#xD;
             metastatic disease&#xD;
&#xD;
          -  The original tumour specimen must be HER2 IHC 3+ positive or, in case of IHC 2+&#xD;
&#xD;
          -  Age ≥18&#xD;
&#xD;
          -  Life expectancy of &gt;12 weeks&#xD;
&#xD;
          -  ECOG PS 0-1&#xD;
&#xD;
          -  Measurable disease as defined by RECIST1.1 criteria&#xD;
&#xD;
          -  All patients must have received prior anthracycline-and taxane-based regimens as well&#xD;
             as trastuzumab based regimens in either the adjuvant or the metastatic setting.&#xD;
             Patients must have been already treated with at least one line of the anti HER2&#xD;
             inhibitor therapy lapatinib for their metastatic breast cancer. A maximum of three&#xD;
             previous lines of anti-HER-2 therapies in the metastatic setting are allowed.&#xD;
&#xD;
          -  Adequate haematological function as defined by: ANC 1.5 x 109/L, platelet count 100 x&#xD;
             109/L, haemoglobin 10 g/dL.&#xD;
&#xD;
          -  Adequate renal function, as defined by: creatinine 1.5 x UNL&#xD;
&#xD;
          -  Adequate hepatobiliary function, as defined by the following baseline liver function&#xD;
             tests: total serum bilirubin 1.5 upper normal limit (UNL); alanine amino transferase&#xD;
             (ALT), aspartate amino transferase (AST) 2.5xUNL; alkaline phosphatase (AP) 2.5xUNL;&#xD;
             if total alkaline phosphatase (AP) &gt; 2.5xUNL, alkaline phosphatase liver fraction must&#xD;
             be 2.5xUNL&#xD;
&#xD;
          -  Adequate contraception for all fertile patients&#xD;
&#xD;
          -  Negative pregnancy test.&#xD;
&#xD;
          -  Postmenopausal women fulfilling any of the NCCN criteria may be included.&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) ≥50% during a baseline period of 28 days, as&#xD;
             determined by either echocardiography (ECHO) or multi gated acquisition (MUGA) scan.&#xD;
&#xD;
          -  Signed, written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of persistent Grade ≥ 2 hematologic toxicity resulting from previous systemic&#xD;
             therapy&#xD;
&#xD;
          -  Current peripheral neuropathy of NCI-CTCAE, Version 3.0, Grade ≥ 3 at randomization&#xD;
&#xD;
          -  History of other malignancy within the last 5 years, except for carcinoma in situ of&#xD;
             the cervix or basal cell carcinoma&#xD;
&#xD;
          -  Bone-only disease, unless a measurable lesion is evident as determined by RECIST v1.1&#xD;
&#xD;
          -  Bone scan, PET scan or plain films are not considered adequate imaging techniques to&#xD;
             measure bone lesions. ve&#xD;
&#xD;
          -  Blastic bone lesions are non-measurable.&#xD;
&#xD;
          -  Uncontrolled hypertension (systolic &gt;150 mm Hg and/or diastolic &gt;100 mm Hg) or&#xD;
             clinically significant (i.e. active) cardiovascular disease.&#xD;
&#xD;
          -  Current dyspnoea at rest due to complications of advanced malignancy, or other&#xD;
             diseases that require continuous oxygen therapy.&#xD;
&#xD;
          -  Inadequate organ function, evidenced by the following laboratory results within 28&#xD;
             days prior to randomization.&#xD;
&#xD;
          -  Current severe, uncontrolled systemic disease&#xD;
&#xD;
          -  Major surgical procedure or significant traumatic injury within 28 days prior to study&#xD;
             treatment start or anticipation of the need for major surgery during the course of&#xD;
             study treatment&#xD;
&#xD;
          -  History of receiving any investigational treatment within 28 days of randomization&#xD;
&#xD;
          -  Current known infection with HIV, HBV, or HCV&#xD;
&#xD;
          -  Receipt of IV antibiotics for infection within 14 days of randomization&#xD;
&#xD;
          -  Known hypersensitivity to any of the study drugs&#xD;
&#xD;
          -  Assessed by the investigator to be unable or unwilling to comply with the requirements&#xD;
             of the protocol&#xD;
&#xD;
          -  Lack of physical integrity of the upper gastrointestinal tract, clinically significant&#xD;
             malabsorption syndrome, or inability to take oral medications&#xD;
&#xD;
          -  Concurrent interventional or non-interventional studies&#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>Grazia Arpino, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli &quot;Federico II&quot;</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Clinical Research Technology</last_name>
    <phone>0039089301545</phone>
  </overall_contact>
  <location>
    <facility>
      <name>A.O.U. Ospedali Riuniti Umberto I</name>
      <address>
        <city>Ancona</city>
        <zip>60020</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Stefano Cascinu, MD</last_name>
    </contact>
    <investigator>
      <last_name>Stefano Cascinu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centro di Riferimento Oncologico</name>
      <address>
        <city>Aviano</city>
        <zip>33081</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Simon Spazzapan, MD</last_name>
    </contact>
    <investigator>
      <last_name>Simon Spazzapan, Md</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Policlinico S. Orsola Malpighi</name>
      <address>
        <city>Bologna</city>
        <zip>MD</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Claudio Zamagni, MD</last_name>
    </contact>
    <investigator>
      <last_name>Claudio Zamagni, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale Centrale di Bolzano</name>
      <address>
        <city>Bolzano</city>
        <zip>39100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Elisabetta Cretella, MD</last_name>
    </contact>
    <investigator>
      <last_name>Elisabetta Cretella, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Presidio Ospedaliero 'Antonio Perrino</name>
      <address>
        <city>Brindisi</city>
        <zip>72100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Saverio Cinieri, MD</last_name>
    </contact>
    <investigator>
      <last_name>Saverio Cinieri, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>A.O.R.N.A.S. Garibaldi Nesima di Catania</name>
      <address>
        <city>Catania</city>
        <zip>95122</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Roberto Bordonaro, MD</last_name>
    </contact>
    <investigator>
      <last_name>Roberto Bordonaro, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Humanitas Centro Catanese di Oncologia</name>
      <address>
        <city>Catania</city>
        <zip>95126</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Michele Caruso, MD</last_name>
    </contact>
    <investigator>
      <last_name>Michele Caruso, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera S. Anna</name>
      <address>
        <city>Como</city>
        <zip>22100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Monica Giordano, MD</last_name>
    </contact>
    <investigator>
      <last_name>Monica Giordano, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale 'F. Spaziani'</name>
      <address>
        <city>Frosinone</city>
        <zip>03100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Teresa Gamucci, MD</last_name>
    </contact>
    <investigator>
      <last_name>Teresa Gamucci, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>I.R.C.C.S. A.O.U. San Martino</name>
      <address>
        <city>Genova</city>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lucia Del Mastro, MD</last_name>
    </contact>
    <investigator>
      <last_name>Lucia Del Mastro, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale Civile di Guastalla</name>
      <address>
        <city>Guastalla</city>
        <zip>42016</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Laura Scaltriti, Md</last_name>
    </contact>
    <investigator>
      <last_name>Laura Scaltriti, Md</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale Vito Fazzi</name>
      <address>
        <city>Lecce</city>
        <zip>73100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mariangela Ciccarese, MD</last_name>
    </contact>
    <investigator>
      <last_name>Mariangela Ciccarese, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale di Lugo - AUSL della Romagna</name>
      <address>
        <city>Lugo</city>
        <zip>48022</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Michele Gianni Turolla, MD</last_name>
    </contact>
    <investigator>
      <last_name>Michele Gianni Turolla, Md</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori</name>
      <address>
        <city>Meldola</city>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dino Amadori, MD</last_name>
    </contact>
    <investigator>
      <last_name>Dino Amadori, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale Niguarda Ca' Granda</name>
      <address>
        <city>Milano</city>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Salvatore Siena, Md</last_name>
    </contact>
    <investigator>
      <last_name>Salvatore Siena, Md</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>A.O. San Gerardo</name>
      <address>
        <city>Monza</city>
        <zip>20900</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marina Elena Cazzaniga, MD</last_name>
      <phone>039-233.3683</phone>
      <email>ricercaindipendente.monza@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Marina Elena Cazzaniga, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>AORN &quot;A. Cardarelli&quot;</name>
      <address>
        <city>Naples</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nando Riccardi, MD</last_name>
      <phone>08174721740</phone>
      <email>nando.riccardi@alice.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori - IRCCS &quot;Fondazione G.Pascale&quot;</name>
      <address>
        <city>Napoli</city>
        <zip>8011</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michele De Laurentiis, MD</last_name>
    </contact>
    <investigator>
      <last_name>Michele De Laurentiis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Policlinico SUN</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Michele Orditura, MD</last_name>
    </contact>
    <investigator>
      <last_name>Michele Orditura, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Università degli Studi di Napoli &quot;Federico II&quot;</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Grazia Arpino, MD</last_name>
    </contact>
    <investigator>
      <last_name>Grazia Arpino, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>A.R.N.A.S. Ospedale Civico e Benfratelli</name>
      <address>
        <city>Palermo</city>
        <zip>90127</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vita Leonardi, MD</last_name>
    </contact>
    <investigator>
      <last_name>Vita Leonardi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale S. Maria della Misericordia</name>
      <address>
        <city>Perugia</city>
        <zip>06156</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Maria Mosconi, MD</last_name>
    </contact>
    <investigator>
      <last_name>Anna Maria Mosconi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Santa Maria degli Angeli</name>
      <address>
        <city>Pordenone</city>
        <zip>33170</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Silvana Saracchini, MD</last_name>
    </contact>
    <investigator>
      <last_name>Silvana Saracchini, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale di Ravenna</name>
      <address>
        <city>Ravenna</city>
        <zip>48100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Claudio Dazzi, MD</last_name>
    </contact>
    <investigator>
      <last_name>Dazzi Claudio, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia</name>
      <address>
        <city>Reggio Emilia</city>
        <zip>42123</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Corrado Boni, MD</last_name>
    </contact>
    <investigator>
      <last_name>Corrado Boni, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale Infermi di Rimini</name>
      <address>
        <city>Rimini</city>
        <zip>47923</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lorenzo Gianni, MD</last_name>
    </contact>
    <investigator>
      <last_name>Lorenzo Gianni, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario Campus Biomedico</name>
      <address>
        <city>Roma</city>
        <zip>00128</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Giuseppe Tonini, Md</last_name>
    </contact>
    <investigator>
      <last_name>Giuseppe Tonini, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Istituto Regina Elena per lo studio e la cura dei tumori</name>
      <address>
        <city>Roma</city>
        <zip>00144</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francesco Cognetti, Md</last_name>
    </contact>
    <investigator>
      <last_name>Cognetti Francesco, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale G. Da Procida</name>
      <address>
        <city>Salerno</city>
        <zip>84126</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Maria Luisa Barzelloni, MD</last_name>
    </contact>
    <investigator>
      <last_name>Maria Luisa Barzelloni, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale Civile di Sassari SS Annunaziata</name>
      <address>
        <city>Sassari</city>
        <zip>07100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nina Olmeo, MD</last_name>
    </contact>
    <investigator>
      <last_name>Nina Olmeo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale 'SS. Trinità'</name>
      <address>
        <city>Sora</city>
        <zip>03039</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Teresa Gamucci, MD</last_name>
    </contact>
    <investigator>
      <last_name>Teresa Gamucci, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera S.Maria di Terni</name>
      <address>
        <city>Terni</city>
        <zip>05100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fauso Roila, Md</last_name>
    </contact>
    <investigator>
      <last_name>Fausto Roila, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>A.O.U. San Giovanni Battista di Torino</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Mario Airoldi, MD</last_name>
    </contact>
    <investigator>
      <last_name>Mario Airoldi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>A.O.U. Santa Maria della Misericordia di Udine</name>
      <address>
        <city>Udine</city>
        <zip>33100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>fabio Puglisi, MD</last_name>
    </contact>
    <investigator>
      <last_name>Fabio Puglisi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>A.O. Ospedale di Circolo e Fondazione Macchi</name>
      <address>
        <city>Varese</city>
        <zip>21100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Giovanni Giardina, MD</last_name>
    </contact>
    <investigator>
      <last_name>Giovanni Giardina, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale Sacro Cuore Don Calabria</name>
      <address>
        <city>Verona</city>
        <zip>37024</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Stefania Gori, MD</last_name>
    </contact>
    <investigator>
      <last_name>Stefania Gori, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Nahta R, Esteva FJ. Herceptin: mechanisms of action and resistance. Cancer Lett. 2006 Feb 8;232(2):123-38. doi: 10.1016/j.canlet.2005.01.041.</citation>
    <PMID>16458110</PMID>
  </reference>
  <reference>
    <citation>Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol. 2006 May;3(5):269-80. doi: 10.1038/ncponc0509.</citation>
    <PMID>16683005</PMID>
  </reference>
  <reference>
    <citation>Jagiello-Gruszfeld A, Tjulandin S, Dobrovolskaya N, Manikhas A, Pienkowski T, DeSilvio M, Ridderheim M, Abbey R. A single-arm phase II trial of first-line paclitaxel in combination with lapatinib in HER2-overexpressing metastatic breast cancer. Oncology. 2010;79(1-2):129-35. doi: 10.1159/000318043. Epub 2010 Nov 22.</citation>
    <PMID>21088439</PMID>
  </reference>
  <reference>
    <citation>Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320. Erratum In: N Engl J Med. 2007 Apr 5;356(14):1487.</citation>
    <PMID>17192538</PMID>
  </reference>
  <reference>
    <citation>Clemens M, Eidtmann H, Nitz U, Niederle N, du Bois A, Grischke EM, Hinke A, von Minckwitz G. Trastuzumab single-drug therapy after failure of cytotoxic treatment for metastatic breast cancer. Onkologie. 2010;33(8-9):425-30. doi: 10.1159/000318144. Epub 2010 Jul 27.</citation>
    <PMID>20838057</PMID>
  </reference>
  <reference>
    <citation>von Minckwitz G, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, Maartense E, de Jongh FE, Baumann KH, Bischoff J, Harbeck N, Luck HJ, Maass N, Zielinski C, Andersson M, Stein RC, Nekljudova V, Loibl S; GBG 26/BIG 03-05 study group and participating investigators. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer. 2011 Oct;47(15):2273-81. doi: 10.1016/j.ejca.2011.06.021. Epub 2011 Jul 7.</citation>
    <PMID>21741829</PMID>
  </reference>
  <reference>
    <citation>Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, Ellis C, Casey M, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010 Mar 1;28(7):1124-30. doi: 10.1200/JCO.2008.21.4437. Epub 2010 Feb 1.</citation>
    <PMID>20124187</PMID>
  </reference>
  <reference>
    <citation>Wu Y, Amonkar MM, Sherrill BH, O'Shaughnessy J, Ellis C, Baselga J, Blackwell KL, Burstein HJ. Impact of lapatinib plus trastuzumab versus single-agent lapatinib on quality of life of patients with trastuzumab-refractory HER2+ metastatic breast cancer. Ann Oncol. 2011 Dec;22(12):2582-2590. doi: 10.1093/annonc/mdr014. Epub 2011 Mar 15. Erratum In: Ann Oncol. 2019 Jun 1;30(6):1019.</citation>
    <PMID>21406472</PMID>
  </reference>
  <reference>
    <citation>Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. doi: 10.1200/JCO.2009.23.3734. Epub 2009 Sep 28.</citation>
    <PMID>19786658</PMID>
  </reference>
  <reference>
    <citation>Page K, Hava N, Ward B, Brown J, Guttery DS, Ruangpratheep C, Blighe K, Sharma A, Walker RA, Coombes RC, Shaw JA. Detection of HER2 amplification in circulating free DNA in patients with breast cancer. Br J Cancer. 2011 Apr 12;104(8):1342-8. doi: 10.1038/bjc.2011.89. Epub 2011 Mar 22.</citation>
    <PMID>21427727</PMID>
  </reference>
  <reference>
    <citation>Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. doi: 10.1056/NEJMoa052122.</citation>
    <PMID>16236738</PMID>
  </reference>
  <reference>
    <citation>Wang YC, Morrison G, Gillihan R, Guo J, Ward RM, Fu X, Botero MF, Healy NA, Hilsenbeck SG, Phillips GL, Chamness GC, Rimawi MF, Osborne CK, Schiff R. Different mechanisms for resistance to trastuzumab versus lapatinib in HER2-positive breast cancers--role of estrogen receptor and HER2 reactivation. Breast Cancer Res. 2011;13(6):R121. doi: 10.1186/bcr3067. Epub 2011 Nov 28.</citation>
    <PMID>22123186</PMID>
  </reference>
  <reference>
    <citation>Tan-Chiu E, Yothers G, Romond E, Geyer CE Jr, Ewer M, Keefe D, Shannon RP, Swain SM, Brown A, Fehrenbacher L, Vogel VG, Seay TE, Rastogi P, Mamounas EP, Wolmark N, Bryant J. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005 Nov 1;23(31):7811-9. doi: 10.1200/JCO.2005.02.4091.</citation>
    <PMID>16258083</PMID>
  </reference>
  <reference>
    <citation>Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. doi: 10.1056/NEJM200103153441101.</citation>
    <PMID>11248153</PMID>
  </reference>
  <reference>
    <citation>Rusnak DW, Lackey K, Affleck K, Wood ER, Alligood KJ, Rhodes N, Keith BR, Murray DM, Knight WB, Mullin RJ, Gilmer TM. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther. 2001 Dec;1(2):85-94.</citation>
    <PMID>12467226</PMID>
  </reference>
  <verification_date>June 2016</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>June 14, 2016</last_update_submitted>
  <last_update_submitted_qc>June 14, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 15, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Breast cancer</keyword>
  <keyword>HER2 Positive</keyword>
  <keyword>HER2+</keyword>
  <keyword>MBC</keyword>
  <keyword>Metastatic</keyword>
  <keyword>Metastatic breast cancer</keyword>
  <keyword>Chemotherapy</keyword>
  <keyword>Lapatinib</keyword>
  <keyword>Trastuzumab</keyword>
  <keyword>anti HER2 therapies</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Lapatinib</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/NCT02238509
org study id: GIM12-TYPHER
secondary id: 2013-005044-29
nct id: NCT02238509
lead sponsor: 
collaborator: 
has dmc: Yes
Recent clinical studies have shown that the combination of lapatinib and trastuzumab has
      superior antitumor activity compared to either single drug in both neoadjuvant and metastatic
      setting and is well tolerated. According to this evidence, the combination of lapatinib and
      trastuzumab today offers a valid chemotherapy-free option, primarily for patients with
      pre-treated HER2-positive MBC
The present study is designed to determine the efficacy and safety profile of the combination
      of lapatinib and trastuzumab (plus endocrinetherapy in ER-positive breast cancer) versus
      trastuzumab and chemotherapy in heavily pretreated patient population with HER2-positive MBC
      and to investigate the predictive role of cfDNA for detection of HER2 gene amplification on
      patients' outcome. The presence of circulating free DNA (cfDNA) for detection of HER2 gene
      amplification was associated with worse prognosis and seems to allow early response
      evaluation. However, many aspects of the role of cfDNA detection in patients undergoing
      molecular target agents such as trastuzumab or lapatinib are not well described. With the
      availability of improved and standardized techniques for cfDNA detection, it should now be
      possible to examine several of these important questions within a prospective multicenter
      study and a striking potential of cfDNA for detection of HER2 gene amplification might enable
      a more individual and optimized antimetastatic therapy inpatients with cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical Benefit Rate
time frame: Clinical Benefit Rate is defined as confirmed complete response plus partial response at any time, plus stable disease up to 24 weeks
description: To evaluate clinical benefit rate (CBR) for patients treated with lapatinib and trastuzumab and for patients treated with trastuzumab and chemotherapy. CBR is defined as: confirmed complete response (CR) plus partial response (PR) at any time, plus stable disease (SD) for 24 weeks
measure: Progression free survival
time frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months
description: Second-line progression-free survival, defined as the time from first dosing to the first documented disease progression or death from any cause, whichever occurs first.
measure: Overall Survival
time frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months
description: OS is defined as the time from first dosing in second line to death from any cause.
measure: Safety and tolerability
time frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months
description: Safety of second line treatment will be evaluated by the frequency of AEs and SAEs, cardiac events, clinically significant abnormal laboratory tests, vital signs, and ECOG PS. All patients who received at least one dose of study treatment will be included in the safety analysis.
measure: Quality of life
time frame: Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first, assessed up to 36 months
description: QoL and symptom control will be assessed using the FACT-B questionnaire.
arm group label: lapatinib and trastuzumab
arm group type: Experimental
description: ARM A: Lapatinib and trastuzumab (experimental arm). Patients with hormone receptor (HR) positive breast cancer will also receive endocrine therapy at the physician's discretion (preferred choice with fulvestrant).
arm group label: trastuzumab plus chemotherapy
arm group type: Experimental
description: ARM B: Trastuzumab plus chemotherapy (control arm). Any type of chemotherapy in combination with trastuzumab will be allowed at the physician's discretion.
intervention type: Drug
intervention name: Lapatinib
description: ARM A: oral lapatinib 1,000 mg daily in combination with intravenous trastuzumab 6mg/kg q3wks (after the initial 8 mg/kg loading dose).
arm group label: lapatinib and trastuzumab
other name: Tyverb
intervention type: Drug
intervention name: Trastuzumab
description: ARM A: oral lapatinib 1,000 mg daily in combination with intravenous trastuzumab 6mg/kg q3wks (after the initial 8 mg/kg loading dose).
arm group label: lapatinib and trastuzumab
arm group label: trastuzumab plus chemotherapy
other name: Herceptin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Grazia Arpino, MD
role: Principal Investigator
affiliation: Dipartimento di Medicina Clinica e Chirurgia Oncologia Università degli Studi di Napoli "Federico II"
last name: Clinical Research Technology
phone: 0039089301545
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
country: Italy
citation: Nahta R, Esteva FJ. Herceptin: mechanisms of action and resistance. Cancer Lett. 2006 Feb 8;232(2):123-38. doi: 10.1016/j.canlet.2005.01.041.
PMID: 16458110
citation: Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol. 2006 May;3(5):269-80. doi: 10.1038/ncponc0509.
PMID: 16683005
citation: Jagiello-Gruszfeld A, Tjulandin S, Dobrovolskaya N, Manikhas A, Pienkowski T, DeSilvio M, Ridderheim M, Abbey R. A single-arm phase II trial of first-line paclitaxel in combination with lapatinib in HER2-overexpressing metastatic breast cancer. Oncology. 2010;79(1-2):129-35. doi: 10.1159/000318043. Epub 2010 Nov 22.
PMID: 21088439
citation: Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320. Erratum In: N Engl J Med. 2007 Apr 5;356(14):1487.
PMID: 17192538
citation: Clemens M, Eidtmann H, Nitz U, Niederle N, du Bois A, Grischke EM, Hinke A, von Minckwitz G. Trastuzumab single-drug therapy after failure of cytotoxic treatment for metastatic breast cancer. Onkologie. 2010;33(8-9):425-30. doi: 10.1159/000318144. Epub 2010 Jul 27.
PMID: 20838057
citation: von Minckwitz G, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, Maartense E, de Jongh FE, Baumann KH, Bischoff J, Harbeck N, Luck HJ, Maass N, Zielinski C, Andersson M, Stein RC, Nekljudova V, Loibl S; GBG 26/BIG 03-05 study group and participating investigators. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer. 2011 Oct;47(15):2273-81. doi: 10.1016/j.ejca.2011.06.021. Epub 2011 Jul 7.
PMID: 21741829
citation: Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, Ellis C, Casey M, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010 Mar 1;28(7):1124-30. doi: 10.1200/JCO.2008.21.4437. Epub 2010 Feb 1.
PMID: 20124187
citation: Wu Y, Amonkar MM, Sherrill BH, O'Shaughnessy J, Ellis C, Baselga J, Blackwell KL, Burstein HJ. Impact of lapatinib plus trastuzumab versus single-agent lapatinib on quality of life of patients with trastuzumab-refractory HER2+ metastatic breast cancer. Ann Oncol. 2011 Dec;22(12):2582-2590. doi: 10.1093/annonc/mdr014. Epub 2011 Mar 15. Erratum In: Ann Oncol. 2019 Jun 1;30(6):1019.
PMID: 21406472
citation: Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. doi: 10.1200/JCO.2009.23.3734. Epub 2009 Sep 28.
PMID: 19786658
citation: Page K, Hava N, Ward B, Brown J, Guttery DS, Ruangpratheep C, Blighe K, Sharma A, Walker RA, Coombes RC, Shaw JA. Detection of HER2 amplification in circulating free DNA in patients with breast cancer. Br J Cancer. 2011 Apr 12;104(8):1342-8. doi: 10.1038/bjc.2011.89. Epub 2011 Mar 22.
PMID: 21427727
citation: Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. doi: 10.1056/NEJMoa052122.
PMID: 16236738
citation: Wang YC, Morrison G, Gillihan R, Guo J, Ward RM, Fu X, Botero MF, Healy NA, Hilsenbeck SG, Phillips GL, Chamness GC, Rimawi MF, Osborne CK, Schiff R. Different mechanisms for resistance to trastuzumab versus lapatinib in HER2-positive breast cancers--role of estrogen receptor and HER2 reactivation. Breast Cancer Res. 2011;13(6):R121. doi: 10.1186/bcr3067. Epub 2011 Nov 28.
PMID: 22123186
citation: Tan-Chiu E, Yothers G, Romond E, Geyer CE Jr, Ewer M, Keefe D, Shannon RP, Swain SM, Brown A, Fehrenbacher L, Vogel VG, Seay TE, Rastogi P, Mamounas EP, Wolmark N, Bryant J. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005 Nov 1;23(31):7811-9. doi: 10.1200/JCO.2005.02.4091.
PMID: 16258083
citation: Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. doi: 10.1056/NEJM200103153441101.
PMID: 11248153
citation: Rusnak DW, Lackey K, Affleck K, Wood ER, Alligood KJ, Rhodes N, Keith BR, Murray DM, Knight WB, Mullin RJ, Gilmer TM. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther. 2001 Dec;1(2):85-94.
PMID: 12467226
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Trastuzumab
mesh term: Lapatinib
sharing ipd: No