<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/NCT04464174</url>
  </required_header>
  <id_info>
    <org_study_id>MedOPP253</org_study_id>
    <secondary_id>2018-004648-44</secondary_id>
    <nct_id>NCT04464174</nct_id>
  </id_info>
  <brief_title>Ipatasertib Plus Non-Taxane Chemotherapy for Advanced or Metastatic Triple-Negative Breast Cancer</brief_title>
  <acronym>PATHFINDER</acronym>
  <official_title>A Multicenter, Open-Label, Non-Comparative, Three-Arm, Phase IIa Trial of Ipatasertib (GDC-0068) in Combination With Non-Taxane Chemotherapy Agents for Taxane-Pretreated Unresectable Locally Advanced or Metastatic TNBC Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MedSIR</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>MedSIR</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, open-label, non-comparative, three-arm, phase IIa trial of Ipatasertib&#xD;
      (GDC-0068) in combination with non-taxane chemotherapy agents for taxane-pretreated&#xD;
      unresectable locally advanced or metastatic triple-negative breast cancer patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Women age ≥ 18 years with triple-negative unresectable locally advanced or MBC that is not&#xD;
      amenable to resection with curative intent.&#xD;
&#xD;
      Patients must have received at least one, but not more than two, prior chemotherapeutic&#xD;
      regimens for treatment of unresectable locally advanced and/or metastatic disease (at least&#xD;
      one regimen must have contained a taxane).&#xD;
&#xD;
      The number of patients to be included is 54 patients. The primary objective is to evaluate&#xD;
      the safety and tolerability of ipatasertib (GDC-0068) in combination with capecitabine,&#xD;
      eribulin, or carboplatin plus gemcitabine in patients with unresectable locally advanced or&#xD;
      metastatic triple-negative breast cancer&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 8, 2020</start_date>
  <completion_date type="Anticipated">January 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine; as incidence of Adverse Events as assessed by the investigator, with severity determined through the use of NCI-CTCAE v.4.03</measure>
    <time_frame>From baseline up to 15 months</time_frame>
    <description>To evaluate the safety and tolerability of ipatasertib (400 mg) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>From baseline up to 15 months</time_frame>
    <description>PFS, defined as the time from the date of inclusion to the date of the first documented progression or death due to any cause. If a patient has not had an event, PFS will be censored at the date of the last adequate tumor evaluation [see RECIST 1.1]) (Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the Intended To Treat (ITT) population and in each treatment arm).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR)</measure>
    <time_frame>From baseline up to 15 months</time_frame>
    <description>TTR, defined as the time from the treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a Complete Response (CR) or Partial Response (PR), as determined locally by the investigator through the use of RECIST v.1.1.(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>From baseline up to 15 months</time_frame>
    <description>ORR, defined as a CR or PR, as determined locally by the investigator through the use of RECIST v.1.1.(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>From baseline up to 15 months</time_frame>
    <description>DoR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined locally by the investigator through use of RECIST v.1.1.(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate (CBR)</measure>
    <time_frame>From baseline up to 15 months</time_frame>
    <description>CBR, defined as an objective response (CR or PR), or Stable Disease (SD) for at least 24 weeks, as determined locally by the investigator through the use of RECIST v.1.1(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From baseline up to 15 months</time_frame>
    <description>OS, defined as the time from treatment initiation to death from any cause, as determined locally by the investigator through use of RECIST v.1.1.(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best percentage of change from baseline in the size of target tumor lesions</measure>
    <time_frame>From baseline up to 15 months</time_frame>
    <description>Best percentage of change from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease will be observed, as determined locally by the investigator through use of RECIST v.1.1.(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">54</enrollment>
  <condition>Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Ipatasertib plus capecitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm A: Ipatasertib (GDC-0068) 400 milligrams (mg) tablets administered orally once a day (noon) on Days 1-14 of each 21-day cycle plus capecitabine 1000 mg/m2 tablets orally twice a day (morning and evening; equivalent to 2000 mg/m2 total daily dose), for 14 days (followed by a 7-day rest period) every 21-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ipatasertib plus Eribulin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm B: Ipatasertib (GDC-0068) 400 mg tablets administered orally once a day on Days 1-14 of each 21-day cycle plus eribulin 1.23 mg/m2 (equivalent to eribulin mesylate at 1.4 mg/m2) administered intravenously over 2 to 5 minutes on Days 1 and 8 of every 21-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ipatasertib plus carboplatin plus gemcitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm C: Ipatasertib (GDC-0068) 400 mg tablets administered orally once a day on Days 1-14 of each 21-day cycle plus carboplatin AUC5 on Day 1 administered intravenously plus gemcitabine 1000 mg/m2 administered intravenously over 30 minutes on Days 1 and 8, every 21-day cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipatasertib</intervention_name>
    <description>Ipatasertib administered orally (400 mg) once a day, from day 1 to day 14, and rest from day 15 to day 21 of every 21-day cycle</description>
    <arm_group_label>Ipatasertib plus Eribulin</arm_group_label>
    <arm_group_label>Ipatasertib plus capecitabine</arm_group_label>
    <arm_group_label>Ipatasertib plus carboplatin plus gemcitabine</arm_group_label>
    <other_name>GDC-0068</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>Capecitabine administered orally (1000 mg/m2) twice a day, from day 1 to day 14, and rest from day 15 to day 21 of every 21-day cycle</description>
    <arm_group_label>Ipatasertib plus capecitabine</arm_group_label>
    <other_name>Xeloda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eribulin</intervention_name>
    <description>Eribulin 1.23 mg/m2 administered intravenously Days 1 and 8 of every 21-day cycle</description>
    <arm_group_label>Ipatasertib plus Eribulin</arm_group_label>
    <other_name>Halaven</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin AUC5 administered intravenously day 1 of every 21-day cycle</description>
    <arm_group_label>Ipatasertib plus carboplatin plus gemcitabine</arm_group_label>
    <other_name>Paraplatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Gemcitabine administered intravenously (1000 mg/m2) at days 1 and 8 of every 21-day cycle</description>
    <arm_group_label>Ipatasertib plus carboplatin plus gemcitabine</arm_group_label>
    <other_name>Gemzar</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed Informed Consent Form (ICF) prior to participation in any study-related&#xD;
             activities.&#xD;
&#xD;
          2. Female patients ≥ 18 years at the time of signing ICF.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.&#xD;
&#xD;
          4. Life expectancy of ≥ 12 weeks.&#xD;
&#xD;
          5. Histologically confirmed Triple Negative Breast Cancer (TNBC) per American Society of&#xD;
             Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria based on&#xD;
             local testing on the most recent analyzed biopsy. Triple-negative is defined as &lt;1%&#xD;
             expression for estrogen receptor (ER) and progesterone receptor (PgR) and negative for&#xD;
             Human Epidermal Growth Factor Receptor 2 (HER2) (0-1+ by immunohistochemistry (IHC) or&#xD;
             2+ and negative by in situ hybridization [ISH) test].&#xD;
&#xD;
          6. Unresectable locally advanced or metastatic disease documented by computerized&#xD;
             tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to&#xD;
             resection with curative intent.&#xD;
&#xD;
          7. Measurable or evaluable disease as per RECIST v.1.1. Patients with only bone lesions&#xD;
             are also eligible.&#xD;
&#xD;
          8. Refractory to or relapsed after one or two prior standard of care chemotherapy&#xD;
             regimens for unresectable locally advanced or metastatic breast cancer (MBC). Earlier&#xD;
             adjuvant or neoadjuvant therapy for more limited disease will be considered as one of&#xD;
             the required prior regimens if the development of unresectable locally advanced or&#xD;
             metastatic disease occurred within a 12-month period of time after completion of&#xD;
             chemotherapy.&#xD;
&#xD;
             Note: Exclusive tumor marker elevation will not be considered sufficient for diagnosis&#xD;
             of disease progression.&#xD;
&#xD;
          9. Prior therapy must have included a taxane in any combination or order and either in&#xD;
             the early, locally advanced, or metastatic setting. Note: Exclusive prior taxane-based&#xD;
             therapy as adjuvant or neoadjuvant treatment is also allowed if the patient had a&#xD;
             disease-free interval of less than 12 months after completing this treatment.&#xD;
&#xD;
         10. Eligible for one of the chemotherapy options (eribulin, capecitabine, carboplatin plus&#xD;
             gemcitabine) as per local investigator assessment and slots availability. Patients&#xD;
             treated with (neo)adjuvant platinum salts or capecitabine and who have relapsed more&#xD;
             than one year after the last dose of either treatment may be allowed to be included in&#xD;
             the treatment arm based on ipatasertib (GDC-0068) in combination with carboplatin plus&#xD;
             gemcitabine and capecitabine, respectively.&#xD;
&#xD;
         11. Previous treatment with androgen receptor antagonists, poly ADP-ribose Polymerase&#xD;
             (PARP) inhibitors, and immunotherapy is allowed. Those patients who have previously&#xD;
             received a PARP inhibitor will not be included in the carboplatin and gemcitabine arm&#xD;
             unless PARP inhibitors were used in the early breast cancer setting and the period&#xD;
             between the end of PARP inhibitor-based regimen and onset of metastatic disease is at&#xD;
             least of 12 months.&#xD;
&#xD;
         12. Resolution of all acute toxic effects of prior anti-cancer therapy to grade inferior&#xD;
             or equal to 1 as determined by the NCI-CTCAE v.5.0 (except for alopecia or other&#xD;
             toxicities not considered a safety risk for the patient at investigator's discretion).&#xD;
&#xD;
         13. Willingness and ability to provide a tumor biopsy from a metastatic site or the&#xD;
             primary breast tumor at the time of the inclusion in order to perform exploratory&#xD;
             studies. If not feasible, patient eligibility should be evaluated by a Sponsor's&#xD;
             qualified designee. Note: Subjects for whom tumor biopsies cannot be obtained (e.g.,&#xD;
             inaccessible tumor or subject safety concern) may submit an archived metastatic tumor&#xD;
             specimen only upon agreement from the Sponsor.&#xD;
&#xD;
         14. Patients agree to give blood samples (liquid biopsy) at the time of inclusion, after&#xD;
             two cycles of study treatment, and upon progression or study termination.&#xD;
&#xD;
         15. Adequate hematologic and organ function within 14 days before the first study&#xD;
             treatment on Day 1 of Cycle 1, defined by the following:&#xD;
&#xD;
               1. Hematological: White blood cell (WBC) count &gt; 3.0 x 109/L, absolute neutrophil&#xD;
                  count (ANC) &gt; 1.5 x 109/L, platelet count &gt; 100.0 x109/L, and hemoglobin &gt; 9.0&#xD;
                  g/dL.&#xD;
&#xD;
               2. Hepatic: Serum albumin ≥ 3 g/dL; Bilirubin ≤ 1.5 times the upper limit of normal&#xD;
                  (× ULN) (≤ 3 x ULN in the case of Gilbert's disease); aspartate transaminase&#xD;
                  (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (in the case of liver metastases&#xD;
                  ≤ 5 × ULN); alkaline phosphatase (ALP) ≤ 2 × ULN (≤ 5 × ULN in the case of liver&#xD;
                  and/or bone metastases ≤ 5 × ULN).&#xD;
&#xD;
               3. Renal: Serum creatinine &lt; 1.5 × ULN or creatinine clearance ≥ 50 mL/min based on&#xD;
                  Cockcroft-Gault glomerular filtration rate estimation.&#xD;
&#xD;
               4. Coagulation: Partial Thromboplastin Time (PTT) (or activated Partial&#xD;
                  Thromboplastin Time [aPTT]) and International Normalized Ratio (INR) ≤ 1.5 × ULN&#xD;
                  (except for patients receiving anticoagulation therapy).&#xD;
&#xD;
             Note: Patients receiving heparin treatment should have a PTT (or aPTT) ≤ 2.5 × ULN (or&#xD;
             patient value before starting heparin treatment). Patients receiving coumarin&#xD;
             derivatives should have an INR between 2.0 and 3.0 assessed in two consecutive&#xD;
             measurements one to four days apart. Patients should be on a stable anticoagulant&#xD;
             regimen.&#xD;
&#xD;
         16. For women of childbearing potential: agreement to remain abstinent (refrain from&#xD;
             heterosexual intercourse), or to use a highly effective non-hormonal form of&#xD;
             contraception, or two effective forms of contraception, as defined in the protocol&#xD;
             during the treatment period and for at least 28 days after the last dose of&#xD;
             ipatasertib (GDC-0068), three months after the last dose of eribulin, and six months&#xD;
             after the last dose of carboplatin and gemcitabine or capecitabine, whichever occurs&#xD;
             later, and agreement to refrain from donating eggs during this same period. Women of&#xD;
             childbearing potential must have a negative serum pregnancy test before study&#xD;
             treatment initiation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to comply with study and follow-up procedures.&#xD;
&#xD;
          2. Previous treatment with PI3K, mTOR, or AKT inhibitors.&#xD;
&#xD;
          3. Known active uncontrolled or symptomatic central nervous system (CNS) metastases,&#xD;
             carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms,&#xD;
             cerebral edema, and/or progressive growth. Patients with a history of CNS metastases&#xD;
             or cord compression are eligible if they have been definitively treated (e.g.,&#xD;
             radiotherapy, stereotactic surgery), are clinically stable, and off anticonvulsants&#xD;
             and steroids for at least two weeks before first dose of study treatment.&#xD;
&#xD;
          4. Radiotherapy or limited-field palliative radiotherapy within seven days prior to study&#xD;
             enrolment, or patients who have not recovered from radiotherapy-related toxicities to&#xD;
             baseline or grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously&#xD;
             irradiated.&#xD;
&#xD;
          5. Major surgery (defined as requiring general anesthesia) or significant traumatic&#xD;
             injury within 28 days of start of study drug, or patients who have not recovered from&#xD;
             the side effects of any major surgery.&#xD;
&#xD;
          6. Grade ≥ 2 peripheral neuropathy.&#xD;
&#xD;
          7. Grade ≥ 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia.&#xD;
&#xD;
          8. History of type I or type II diabetes mellitus either requiring insulin or with a&#xD;
             baseline fasting glucose &gt; 150 mg/dL (8.3 mmol/L) or high hemoglobin A1c (HbA1c) as&#xD;
             defined as &gt; 7%. Patients who are on a stable dose of oral diabetes medication during&#xD;
             at least weeks prior to initiation of study treatment are eligible for enrolment.&#xD;
&#xD;
          9. Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis,&#xD;
             cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic&#xD;
             infections (pneumocystis pneumonia or cytomegalovirus pneumonia).&#xD;
&#xD;
         10. History of malabsorption syndrome or other condition that would interfere with enteral&#xD;
             absorption or results in the inability or unwillingness to swallow pills.&#xD;
&#xD;
         11. History of or active inflammatory bowel disease (e.g., Crohn's disease and ulcerative&#xD;
             colitis) or active bowel inflammation (e.g., diverticulitis).&#xD;
&#xD;
         12. Known hypersensitivity reaction to any investigational or therapeutic compound or&#xD;
             their incorporated substances.&#xD;
&#xD;
         13. Patients have a concurrent malignancy or malignancy within five years of study&#xD;
             enrollment with the exception of carcinoma in situ of the cervix, non-melanoma skin&#xD;
             carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk&#xD;
             of recurrence, discussion with the Medical Monitor is required.&#xD;
&#xD;
         14. Current known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV).&#xD;
             Patients with past HBV infection or resolved HBV infection (defined as having a&#xD;
             negative hepatitis B surface antibody [HBsAg] test and a positive hepatitis B core&#xD;
             antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Patients&#xD;
             positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is&#xD;
             negative for HCV RNA.&#xD;
&#xD;
         15. Active uncontrolled infection at the time of enrollment.&#xD;
&#xD;
         16. Congenital long QT syndrome or screening QT interval corrected using Fridericia's&#xD;
             formula (QTcF) &gt; 480 milliseconds.&#xD;
&#xD;
         17. Patients have an active cardiac disease or a history of cardiac dysfunction including&#xD;
             any of the following:&#xD;
&#xD;
               1. Unstable angina pectoris or documented myocardial infarction within six months&#xD;
                  prior to study entry.&#xD;
&#xD;
               2. Symptomatic pericarditis.&#xD;
&#xD;
               3. Documented congestive heart failure (New York Heart Association functional&#xD;
                  classification III- IV).&#xD;
&#xD;
               4. Left ventricular ejection fraction (LVEF) &lt; 50% as determined by multiple gated&#xD;
                  acquisition (MUGA) scan or echocardiogram (ECHO).&#xD;
&#xD;
         18. Patients have any of the following cardiac conduction abnormalities:&#xD;
&#xD;
               1. Ventricular arrhythmias except for benign premature ventricular contractions.&#xD;
&#xD;
               2. Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled&#xD;
                  with medication.&#xD;
&#xD;
               3. Conduction abnormality requiring a pacemaker.&#xD;
&#xD;
               4. Other cardiac arrhythmia not controlled with medication.&#xD;
&#xD;
         19. Patients have any other concurrent severe and/or uncontrolled medical condition that&#xD;
             would, in the investigator's judgment contraindicate patient participation in the&#xD;
             clinical study.&#xD;
&#xD;
         20. Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 14 days or five&#xD;
             drug-elimination half-lives, whichever is longer, prior to initiation of study&#xD;
             treatment.&#xD;
&#xD;
         21. Pregnant, breastfeeding, or intending to become pregnant during the study or within 28&#xD;
             days after the last dose of ipatasertib (GDC-0068), three months after the last dose&#xD;
             of eribulin, and six months after the last dose of carboplatin and gemcitabine or&#xD;
             capecitabine, whichever occurs later.&#xD;
&#xD;
         22. Treatment with approved or investigational cancer therapy within 14 days prior to&#xD;
             initiation of study drug.&#xD;
&#xD;
         23. Concurrent participation in other interventional clinical trial.&#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>Antonio Llombart, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MedSIR</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Professor Doutor Fernando Fonseca</name>
      <address>
        <city>Amadora</city>
        <state>Lisboa</state>
        <zip>2720-276</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Champalimaud Clinical Centre - Champalimaud Foundation</name>
      <address>
        <city>Lisboa</city>
        <zip>1400-038</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Português de Oncologia do Porto FG, EPE (IPO-Porto)</name>
      <address>
        <city>Porto</city>
        <zip>4200-072</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Provincial de Castellón</name>
      <address>
        <city>Castellón De La Plana</city>
        <state>Castellón</state>
        <zip>12002</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Donostia</name>
      <address>
        <city>San Sebastián</city>
        <state>Donostia</state>
        <zip>20014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico Universitario Virgen de la Arrixaca</name>
      <address>
        <city>El Palmar</city>
        <state>Murcia</state>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Alicante</name>
      <address>
        <city>Alicante</city>
        <zip>03010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Oncológico Baselga - Hospital Quiron Salud Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08023</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital San Pedro de Alcántara</name>
      <address>
        <city>Cáceres</city>
        <zip>10003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Arnau de Vilanova</name>
      <address>
        <city>Lleida</city>
        <zip>25198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Quiron San Camilo- Ruber Juan Bravo</name>
      <address>
        <city>Madrid</city>
        <zip>28006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Victoria</name>
      <address>
        <city>Málaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Arnau de Vilanova</name>
      <address>
        <city>Valencia</city>
        <zip>46015</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Portugal</country>
    <country>Spain</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>January 18, 2023</last_update_submitted>
  <last_update_submitted_qc>January 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2023</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>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Ipatasertib</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/NCT04464174
org study id: MedOPP253
secondary id: 2018-004648-44
nct id: NCT04464174
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multicenter, open-label, non-comparative, three-arm, phase IIa trial of Ipatasertib
      (GDC-0068) in combination with non-taxane chemotherapy agents for taxane-pretreated
      unresectable locally advanced or metastatic triple-negative breast cancer patients
Women age ≥ 18 years with triple-negative unresectable locally advanced or MBC that is not
      amenable to resection with curative intent.

      Patients must have received at least one, but not more than two, prior chemotherapeutic
      regimens for treatment of unresectable locally advanced and/or metastatic disease (at least
      one regimen must have contained a taxane).

      The number of patients to be included is 54 patients. The primary objective is to evaluate
      the safety and tolerability of ipatasertib (GDC-0068) in combination with capecitabine,
      eribulin, or carboplatin plus gemcitabine in patients with unresectable locally advanced or
      metastatic triple-negative breast cancer
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine; as incidence of Adverse Events as assessed by the investigator, with severity determined through the use of NCI-CTCAE v.4.03
time frame: From baseline up to 15 months
description: To evaluate the safety and tolerability of ipatasertib (400 mg) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine
measure: Progression Free Survival (PFS)
time frame: From baseline up to 15 months
description: PFS, defined as the time from the date of inclusion to the date of the first documented progression or death due to any cause. If a patient has not had an event, PFS will be censored at the date of the last adequate tumor evaluation [see RECIST 1.1]) (Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the Intended To Treat (ITT) population and in each treatment arm).
measure: Time to response (TTR)
time frame: From baseline up to 15 months
description: TTR, defined as the time from the treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a Complete Response (CR) or Partial Response (PR), as determined locally by the investigator through the use of RECIST v.1.1.(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).
measure: Objective response rate (ORR)
time frame: From baseline up to 15 months
description: ORR, defined as a CR or PR, as determined locally by the investigator through the use of RECIST v.1.1.(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).
measure: Duration of Response (DoR)
time frame: From baseline up to 15 months
description: DoR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined locally by the investigator through use of RECIST v.1.1.(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).
measure: Clinical Benefit Rate (CBR)
time frame: From baseline up to 15 months
description: CBR, defined as an objective response (CR or PR), or Stable Disease (SD) for at least 24 weeks, as determined locally by the investigator through the use of RECIST v.1.1(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).
measure: Overall Survival (OS)
time frame: From baseline up to 15 months
description: OS, defined as the time from treatment initiation to death from any cause, as determined locally by the investigator through use of RECIST v.1.1.(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).
measure: Best percentage of change from baseline in the size of target tumor lesions
time frame: From baseline up to 15 months
description: Best percentage of change from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease will be observed, as determined locally by the investigator through use of RECIST v.1.1.(Efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the ITT population and in each treatment arm).
arm group label: Ipatasertib plus capecitabine
arm group type: Experimental
description: Arm A: Ipatasertib (GDC-0068) 400 milligrams (mg) tablets administered orally once a day (noon) on Days 1-14 of each 21-day cycle plus capecitabine 1000 mg/m2 tablets orally twice a day (morning and evening; equivalent to 2000 mg/m2 total daily dose), for 14 days (followed by a 7-day rest period) every 21-day cycle.
arm group label: Ipatasertib plus Eribulin
arm group type: Experimental
description: Arm B: Ipatasertib (GDC-0068) 400 mg tablets administered orally once a day on Days 1-14 of each 21-day cycle plus eribulin 1.23 mg/m2 (equivalent to eribulin mesylate at 1.4 mg/m2) administered intravenously over 2 to 5 minutes on Days 1 and 8 of every 21-day cycle.
arm group label: Ipatasertib plus carboplatin plus gemcitabine
arm group type: Experimental
description: Arm C: Ipatasertib (GDC-0068) 400 mg tablets administered orally once a day on Days 1-14 of each 21-day cycle plus carboplatin AUC5 on Day 1 administered intravenously plus gemcitabine 1000 mg/m2 administered intravenously over 30 minutes on Days 1 and 8, every 21-day cycle.
intervention type: Drug
intervention name: Ipatasertib
description: Ipatasertib administered orally (400 mg) once a day, from day 1 to day 14, and rest from day 15 to day 21 of every 21-day cycle
arm group label: Ipatasertib plus Eribulin
arm group label: Ipatasertib plus capecitabine
arm group label: Ipatasertib plus carboplatin plus gemcitabine
other name: GDC-0068
intervention type: Drug
intervention name: Capecitabine
description: Capecitabine administered orally (1000 mg/m2) twice a day, from day 1 to day 14, and rest from day 15 to day 21 of every 21-day cycle
arm group label: Ipatasertib plus capecitabine
other name: Xeloda
intervention type: Drug
intervention name: Eribulin
description: Eribulin 1.23 mg/m2 administered intravenously Days 1 and 8 of every 21-day cycle
arm group label: Ipatasertib plus Eribulin
other name: Halaven
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin AUC5 administered intravenously day 1 of every 21-day cycle
arm group label: Ipatasertib plus carboplatin plus gemcitabine
other name: Paraplatin
intervention type: Drug
intervention name: Gemcitabine
description: Gemcitabine administered intravenously (1000 mg/m2) at days 1 and 8 of every 21-day cycle
arm group label: Ipatasertib plus carboplatin plus gemcitabine
other name: Gemzar
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Antonio Llombart, MD
role: Principal Investigator
affiliation: MedSIR
facility: 
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country: Portugal
country: Spain
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Carboplatin
mesh term: Gemcitabine
mesh term: Capecitabine
mesh term: Ipatasertib
sharing ipd: No