<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/NCT03006172</url>
  </required_header>
  <id_info>
    <org_study_id>GO39374</org_study_id>
    <secondary_id>2016-003022-17</secondary_id>
    <nct_id>NCT03006172</nct_id>
  </id_info>
  <brief_title>To Evaluate the Safety, Tolerability, and Pharmacokinetics of Inavolisib Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer</brief_title>
  <official_title>A Phase I, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GDC-0077 as a Single Agent in Patients With Locally Advanced or Metastatic PIK3CA-Mutant Solid Tumors and in Combination With Endocrine and Targeted Therapies in Patients With Locally Advanced or Metastatic PIK3CA-Mutant Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Genentech, Inc.</source>
  <brief_summary>
    <textblock>
      This is an open-label, multicenter, Phase I study designed to evaluate the safety,&#xD;
      tolerability, and pharmacokinetics of inavolisib administered orally as a single agent in&#xD;
      patients with locally advanced or metastatic PIK3CA-mutant solid tumors, including breast&#xD;
      cancer, and in combination with standard-of-care endocrine and/or targeted therapies for the&#xD;
      treatment of locally advanced or metastatic PIK3CA-mutant breast cancer. Participants will be&#xD;
      enrolled in two stages: a dose-escalation stage (Stage I) and an expansion stage (Stage II).&#xD;
      Participants will be assigned to one of seven regimens: inavolisib as a single agent (Arm A),&#xD;
      inavolisib in combination with palbociclib and letrozole (Arm B), inavolisib in combination&#xD;
      with letrozole (Arm C), inavolisib in combination with fulvestrant (Arm D), inavolisib in&#xD;
      combination with palbociclib and fulvestrant (Arm E), inavolisib in combination with&#xD;
      palbociclib, fulvestrant, and metformin (Arm F), and inavolisib in combination with&#xD;
      trastuzumab and pertuzumab (and letrozole or fulvestrant, if applicable (Arm G)).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 13, 2016</start_date>
  <completion_date type="Anticipated">November 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Stage 1: Percentage of Participants With Dose Limiting Toxicities</measure>
    <time_frame>Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended Phase II Dose of Inavolisib</measure>
    <time_frame>Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Adverse Events and Serious Adverse Events</measure>
    <time_frame>Day 1 up to 6 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration Time-Curve (AUC) from Time Zero to Infinity (AUCinf) of Inavolisib</measure>
    <time_frame>Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to end of study (EOS; up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC from Time Zero to Dosing Interval (AUC0-tau) of Inavolisib</measure>
    <time_frame>Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-Life of Inavolisib</measure>
    <time_frame>Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of Inavolisib</measure>
    <time_frame>Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Plasma Concentration (Cmin) of Inavolisib</measure>
    <time_frame>Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Cmax (tmax) of Inavolisib</measure>
    <time_frame>Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance (CL/F) of Inavolisib</measure>
    <time_frame>Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio (AR) of Inavolisib at Steady-State</measure>
    <time_frame>Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of Palbociclib</measure>
    <time_frame>Predose (0-2 hours before inavolisib) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of Palbociclib</measure>
    <time_frame>Predose (0-2 hours before inavolisib) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of Letrozole</measure>
    <time_frame>Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of Letrozole</measure>
    <time_frame>Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of Fulvestrant</measure>
    <time_frame>Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of Fulvestrant</measure>
    <time_frame>Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (v1.1)</measure>
    <time_frame>Baseline up to occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions &gt;/=4 weeks apart (up to approximately 6 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response, as Assessed by RECIST v1.1</measure>
    <time_frame>From first occurrence of a documented objective response (CR or PR) to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Clinical Benefit as Assessed by RECIST v1.1</measure>
    <time_frame>Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) as Assessed by RECIST v1.1</measure>
    <time_frame>Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Maximum Standard Uptake Value (SUV) of Tumor Regions of Interest (as assessed by [18] F-fluorodeoxyglucose-positron emission tomography) From Baseline to Approximately 2 Weeks of Inavolisib Treatment</measure>
    <time_frame>Baseline, Week 2</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of Pertuzumab</measure>
    <time_frame>Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of Pertuzumab</measure>
    <time_frame>Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of Trastuzumab</measure>
    <time_frame>Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of Trastuzumab</measure>
    <time_frame>Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days</time_frame>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Anticipated">256</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>Stage I Arm A: Inavolisib Single Agent</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive inavolisib in escalating dose levels with starting dose of 6 milligrams (mg). Participants will receive single dose of inavolisib on Day 1 of Cycle 1 followed by once daily from Day 8 of Cycle 1. (Cycle length: 35 days for Cycle 1 and 28 days for all other cycles). Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage I Arm B: Inavolisib + Palbociclib + Letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive inavolisib in escalating dose levels (starting dose 3 mg) on Days 1-28, palbociclib on Days 1-21, and letrozole on Days 1-28 of each 28-day cycle. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage I Arm C: Inavolisib + Letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive inavolisib in escalating dose levels along with letrozole on Days 1-28 of each 28-day cycle. The starting dose of inavolisib will not exceed the starting dose in Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II Arm B: Inavolisib + Palbociclib + Letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive inavolisib on Days 1-28 in combination with palbociclib on Days 1-21 and letrozole on Days 1-28 of each 28-day cycle. Dose of inavolisib will be decided based on the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II Arm C: Inavolisib + Letrozole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive inavolisib in combination with letrozole on Days 1-28 of each 28-day cycle. Dose of inavolisib will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II Arm D: Inavolisib + Fulvestrant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive inavolisib on Days 1-28 in combination with fulvestrant on Day 1 and 15 of Cycle 1 and then on Day 1 from Cycle 2 (cycle length: 28 days). Dose of inavolisib will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive inavolisib (Days 1-28) in combination with palbociclib (Days 1-21) and fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles)(Cycle = 28 days). Dose of inavolisib will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive inavolisib (Days 1-28) in combination with palbociclib (Days 1-21), fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles) and metformin (Days 1-28)(Cycle = 28 days). Dose of inavolisib will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive inavolisib in combination with trastuzumab and pertuzumab (Days 1-21). Dose of inavolisib will be determined from the results of Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inavolisib</intervention_name>
    <description>Participants will receive oral inavolisib once daily on Days 1-28 of each 28-day cycle (Arms A, B, C, D, E, F) or Days 1-21 of each 21-day cycle (Arm G).</description>
    <arm_group_label>Stage I Arm A: Inavolisib Single Agent</arm_group_label>
    <arm_group_label>Stage I Arm B: Inavolisib + Palbociclib + Letrozole</arm_group_label>
    <arm_group_label>Stage I Arm C: Inavolisib + Letrozole</arm_group_label>
    <arm_group_label>Stage II Arm B: Inavolisib + Palbociclib + Letrozole</arm_group_label>
    <arm_group_label>Stage II Arm C: Inavolisib + Letrozole</arm_group_label>
    <arm_group_label>Stage II Arm D: Inavolisib + Fulvestrant</arm_group_label>
    <arm_group_label>Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant</arm_group_label>
    <arm_group_label>Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin</arm_group_label>
    <arm_group_label>Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab</arm_group_label>
    <other_name>RO7113755, GDC-0077</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fulvestrant</intervention_name>
    <description>Participants will receive fulvestrant 500 mg, administered intramuscularly on Days 1 and 15 of Cycle 1. For subsequent cycles, participants will receive fulvestrant intramuscularly on Day 1 of each cycle.</description>
    <arm_group_label>Stage II Arm D: Inavolisib + Fulvestrant</arm_group_label>
    <arm_group_label>Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant</arm_group_label>
    <arm_group_label>Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.</description>
    <arm_group_label>Stage I Arm B: Inavolisib + Palbociclib + Letrozole</arm_group_label>
    <arm_group_label>Stage I Arm C: Inavolisib + Letrozole</arm_group_label>
    <arm_group_label>Stage II Arm B: Inavolisib + Palbociclib + Letrozole</arm_group_label>
    <arm_group_label>Stage II Arm C: Inavolisib + Letrozole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palbociclib</intervention_name>
    <description>Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.</description>
    <arm_group_label>Stage I Arm B: Inavolisib + Palbociclib + Letrozole</arm_group_label>
    <arm_group_label>Stage II Arm B: Inavolisib + Palbociclib + Letrozole</arm_group_label>
    <arm_group_label>Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant</arm_group_label>
    <arm_group_label>Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Participants will receive oral metformin once daily, starting on Cycle 1, Day 1, as tolerated.</description>
    <arm_group_label>Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <description>Participants will receive trastuzumab, administered by IV infusion on Day 1 of each 21-day cycle, at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg for subsequent cycles, until disease progression or unacceptable toxicity.</description>
    <arm_group_label>Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pertuzumab</intervention_name>
    <description>Participants will receive pertuzumab, administered by IV infusion on Day 1 of each 21-day cycle, at a loading dose of 840 mg for Cycle 1 and a dose of 420 mg for subsequent cycles, until disease progression or unacceptable toxicity.</description>
    <arm_group_label>Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Evaluable or measurable disease per RECIST, Version 1.1 (measurable disease only for&#xD;
             Arm D)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Life expectancy of greater than or equal to (≥) 12 weeks&#xD;
&#xD;
          -  Adequate hematologic and organ function, including blood counts, liver and kidney&#xD;
             function&#xD;
&#xD;
        Stage I Arm A (Inavolisib):&#xD;
&#xD;
        - Locally advanced, recurrent, or metastatic, PIK3CA mutant, incurable solid tumor&#xD;
        malignancy, including breast cancer&#xD;
&#xD;
        Stages I and II, Arms B and C:&#xD;
&#xD;
        - Postmenopausal female participants with locally advanced or metastatic PIK3CA-mutant&#xD;
        HR+/HER2- breast cancer&#xD;
&#xD;
        Stage II, Arms D, E, or F:&#xD;
&#xD;
        - Female participants with locally advanced or metastatic PIK3CA-mutant HR+/HER2- breast&#xD;
        cancer&#xD;
&#xD;
        Stage II Arm D:&#xD;
&#xD;
        - Prior treatment with CDK4/6 inhibitor&#xD;
&#xD;
        Stage II Arm G:&#xD;
&#xD;
          -  Female participants with locally advanced or metastatic PIK3CA-mutant HER2+ breast&#xD;
             cancer&#xD;
&#xD;
          -  Left ventricular ejection fraction 50% or greater&#xD;
&#xD;
        Stages I and II:&#xD;
&#xD;
        - All participants must provide tumor tissue from the primary or metastatic tumor site&#xD;
        obtained from a prior or new biopsy or surgical procedure for detection of PIK3CA mutation&#xD;
        by central laboratory test.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Metaplastic breast cancer&#xD;
&#xD;
          -  History of leptomeningeal disease&#xD;
&#xD;
          -  Type 1 or 2 diabetes requiring anti-hyperglycemic medication&#xD;
&#xD;
          -  Inability or unwillingness to swallow pills&#xD;
&#xD;
          -  Malabsorption syndrome or other condition that would interfere with enteral absorption&#xD;
&#xD;
          -  Known and untreated, or active central nervous system metastases&#xD;
&#xD;
          -  Uncontrolled pleural effusion or ascites&#xD;
&#xD;
          -  Any active infection that could impact patient safety or serious infection requiring&#xD;
             intravenous antibiotics&#xD;
&#xD;
          -  History of other malignancy within 5 years, except for treated carcinoma in situ of&#xD;
             the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer&#xD;
&#xD;
          -  History of or active ventricular dysrhythmias or congestive heart failure requiring&#xD;
             medication or symptomatic coronary heart disease&#xD;
&#xD;
          -  Congenital long QT syndrome, prolonged QT interval, or family history of sudden&#xD;
             unexplained death or long QT syndrome&#xD;
&#xD;
        Stage II Arms B, C, D, and E only:&#xD;
&#xD;
          -  Prior treatment with &gt;1 chemotherapy regimen for metastatic disease&#xD;
&#xD;
          -  Prior treatment with PI3K inhibitor&#xD;
&#xD;
          -  History of significant toxicity related to mTOR inhibitor requiring treatment&#xD;
             discontinuation&#xD;
&#xD;
        Stage II Arms B and E only:&#xD;
&#xD;
        - Prior CDK4/6 inhibitor treatment&#xD;
&#xD;
        Stage II Arm G only:&#xD;
&#xD;
          -  Current uncontrolled hypertension or unstable angina&#xD;
&#xD;
          -  History of congestive heart failure, serious cardiac arrhythmia, or recent myocardial&#xD;
             infarction&#xD;
&#xD;
          -  Prior ejection fraction decrease on trastuzumab&#xD;
&#xD;
          -  Prior cumulative doxorubicin greater than 360 mg/m2&#xD;
&#xD;
          -  Symptomatic active lung disease&#xD;
&#xD;
          -  History of significant toxicity related to trastuzumab and/or pertuzumab requiring&#xD;
             discontinuation of treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Reference Study ID Number: GO39374 https://forpatients.roche.com/</last_name>
    <phone>888-662-6728 (U.S. and Canada)</phone>
    <email>global-roche-genentech-trials@gene.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital.</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>2114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </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>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Philippe Bedard Clinic Toronto</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1L7</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Institut Bergonie</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Barts and the London NHS Trust.</name>
      <address>
        <city>London</city>
        <zip>EC1A 7BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital - London</name>
      <address>
        <city>London</city>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital - Surrey</name>
      <address>
        <city>Surrey</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>France</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>December 27, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <last_update_submitted>September 1, 2023</last_update_submitted>
  <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PIK3CA mutant, Breast Cancer</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>Metformin</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Pertuzumab</mesh_term>
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Fulvestrant</mesh_term>
    <mesh_term>Palbociclib</mesh_term>
    <mesh_term>Inavolisib</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03006172
org study id: GO39374
secondary id: 2016-003022-17
nct id: NCT03006172
lead sponsor: 
This is an open-label, multicenter, Phase I study designed to evaluate the safety,
      tolerability, and pharmacokinetics of inavolisib administered orally as a single agent in
      patients with locally advanced or metastatic PIK3CA-mutant solid tumors, including breast
      cancer, and in combination with standard-of-care endocrine and/or targeted therapies for the
      treatment of locally advanced or metastatic PIK3CA-mutant breast cancer. Participants will be
      enrolled in two stages: a dose-escalation stage (Stage I) and an expansion stage (Stage II).
      Participants will be assigned to one of seven regimens: inavolisib as a single agent (Arm A),
      inavolisib in combination with palbociclib and letrozole (Arm B), inavolisib in combination
      with letrozole (Arm C), inavolisib in combination with fulvestrant (Arm D), inavolisib in
      combination with palbociclib and fulvestrant (Arm E), inavolisib in combination with
      palbociclib, fulvestrant, and metformin (Arm F), and inavolisib in combination with
      trastuzumab and pertuzumab (and letrozole or fulvestrant, if applicable (Arm G)).
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Stage 1: Percentage of Participants With Dose Limiting Toxicities
time frame: Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35)
measure: Recommended Phase II Dose of Inavolisib
time frame: Day 1 up to Day 28 (for Stage 1 Arm A: Day 1 up to Day 35)
measure: Percentage of Participants With Adverse Events and Serious Adverse Events
time frame: Day 1 up to 6 years
measure: Area Under the Concentration Time-Curve (AUC) from Time Zero to Infinity (AUCinf) of Inavolisib
time frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to end of study (EOS; up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
measure: AUC from Time Zero to Dosing Interval (AUC0-tau) of Inavolisib
time frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
measure: Half-Life of Inavolisib
time frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
measure: Maximum Plasma Concentration (Cmax) of Inavolisib
time frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
measure: Minimum Plasma Concentration (Cmin) of Inavolisib
time frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
measure: Time to Cmax (tmax) of Inavolisib
time frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
measure: Apparent Clearance (CL/F) of Inavolisib
time frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
measure: Accumulation Ratio (AR) of Inavolisib at Steady-State
time frame: Predose (0-2 hours before dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days (Cycle 1 of Stage 1 Arm A=35 days)
measure: AUC of Palbociclib
time frame: Predose (0-2 hours before inavolisib) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days
measure: Cmax of Palbociclib
time frame: Predose (0-2 hours before inavolisib) dosing) on Cycle 1 Day 1 up to Cycle 6; Cycle length=28 days
measure: AUC of Letrozole
time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
measure: Cmax of Letrozole
time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
measure: AUC of Fulvestrant
time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
measure: Cmax of Fulvestrant
time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=28 days
measure: Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 (v1.1)
time frame: Baseline up to occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions >/=4 weeks apart (up to approximately 6 years)
measure: Duration of Response, as Assessed by RECIST v1.1
time frame: From first occurrence of a documented objective response (CR or PR) to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
measure: Percentage of Participants With Clinical Benefit as Assessed by RECIST v1.1
time frame: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
measure: Progression Free Survival (PFS) as Assessed by RECIST v1.1
time frame: Baseline up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years)
measure: Change in Maximum Standard Uptake Value (SUV) of Tumor Regions of Interest (as assessed by [18] F-fluorodeoxyglucose-positron emission tomography) From Baseline to Approximately 2 Weeks of Inavolisib Treatment
time frame: Baseline, Week 2
measure: AUC of Pertuzumab
time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
measure: Cmax of Pertuzumab
time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
measure: AUC of Trastuzumab
time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
measure: Cmax of Trastuzumab
time frame: Predose (0-2 hours before inavolisib dosing) on Cycle 1 Day 1 up to EOS (up to approximately 6 years); Cycle length=21 days
arm group label: Stage I Arm A: Inavolisib Single Agent
arm group type: Experimental
description: Participants will receive inavolisib in escalating dose levels with starting dose of 6 milligrams (mg). Participants will receive single dose of inavolisib on Day 1 of Cycle 1 followed by once daily from Day 8 of Cycle 1. (Cycle length: 35 days for Cycle 1 and 28 days for all other cycles). Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
arm group label: Stage I Arm B: Inavolisib + Palbociclib + Letrozole
arm group type: Experimental
description: Participants will receive inavolisib in escalating dose levels (starting dose 3 mg) on Days 1-28, palbociclib on Days 1-21, and letrozole on Days 1-28 of each 28-day cycle. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
arm group label: Stage I Arm C: Inavolisib + Letrozole
arm group type: Experimental
description: Participants will receive inavolisib in escalating dose levels along with letrozole on Days 1-28 of each 28-day cycle. The starting dose of inavolisib will not exceed the starting dose in Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
arm group label: Stage II Arm B: Inavolisib + Palbociclib + Letrozole
arm group type: Experimental
description: Participants will receive inavolisib on Days 1-28 in combination with palbociclib on Days 1-21 and letrozole on Days 1-28 of each 28-day cycle. Dose of inavolisib will be decided based on the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
arm group label: Stage II Arm C: Inavolisib + Letrozole
arm group type: Experimental
description: Participants will receive inavolisib in combination with letrozole on Days 1-28 of each 28-day cycle. Dose of inavolisib will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
arm group label: Stage II Arm D: Inavolisib + Fulvestrant
arm group type: Experimental
description: Participants will receive inavolisib on Days 1-28 in combination with fulvestrant on Day 1 and 15 of Cycle 1 and then on Day 1 from Cycle 2 (cycle length: 28 days). Dose of inavolisib will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
arm group label: Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant
arm group type: Experimental
description: Participants will receive inavolisib (Days 1-28) in combination with palbociclib (Days 1-21) and fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles)(Cycle = 28 days). Dose of inavolisib will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
arm group label: Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin
arm group type: Experimental
description: Participants will receive inavolisib (Days 1-28) in combination with palbociclib (Days 1-21), fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles) and metformin (Days 1-28)(Cycle = 28 days). Dose of inavolisib will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
arm group label: Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab
arm group type: Experimental
description: Participants will receive inavolisib in combination with trastuzumab and pertuzumab (Days 1-21). Dose of inavolisib will be determined from the results of Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
intervention type: Drug
intervention name: Inavolisib
description: Participants will receive oral inavolisib once daily on Days 1-28 of each 28-day cycle (Arms A, B, C, D, E, F) or Days 1-21 of each 21-day cycle (Arm G).
arm group label: Stage I Arm A: Inavolisib Single Agent
arm group label: Stage I Arm B: Inavolisib + Palbociclib + Letrozole
arm group label: Stage I Arm C: Inavolisib + Letrozole
arm group label: Stage II Arm B: Inavolisib + Palbociclib + Letrozole
arm group label: Stage II Arm C: Inavolisib + Letrozole
arm group label: Stage II Arm D: Inavolisib + Fulvestrant
arm group label: Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant
arm group label: Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin
arm group label: Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab
other name: RO7113755, GDC-0077
intervention type: Drug
intervention name: Fulvestrant
description: Participants will receive fulvestrant 500 mg, administered intramuscularly on Days 1 and 15 of Cycle 1. For subsequent cycles, participants will receive fulvestrant intramuscularly on Day 1 of each cycle.
arm group label: Stage II Arm D: Inavolisib + Fulvestrant
arm group label: Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant
arm group label: Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin
intervention type: Drug
intervention name: Letrozole
description: Participants will receive once daily oral doses of letrozole 2.5 mg on Days 1-28 of each cycle.
arm group label: Stage I Arm B: Inavolisib + Palbociclib + Letrozole
arm group label: Stage I Arm C: Inavolisib + Letrozole
arm group label: Stage II Arm B: Inavolisib + Palbociclib + Letrozole
arm group label: Stage II Arm C: Inavolisib + Letrozole
intervention type: Drug
intervention name: Palbociclib
description: Participants will receive once daily oral doses of palbociclib 125 mg on Days 1-21 of each cycle.
arm group label: Stage I Arm B: Inavolisib + Palbociclib + Letrozole
arm group label: Stage II Arm B: Inavolisib + Palbociclib + Letrozole
arm group label: Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant
arm group label: Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin
intervention type: Drug
intervention name: Metformin
description: Participants will receive oral metformin once daily, starting on Cycle 1, Day 1, as tolerated.
arm group label: Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin
intervention type: Drug
intervention name: Trastuzumab
description: Participants will receive trastuzumab, administered by IV infusion on Day 1 of each 21-day cycle, at a loading dose of 8 mg/kg for Cycle 1 and a dose of 6 mg/kg for subsequent cycles, until disease progression or unacceptable toxicity.
arm group label: Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab
intervention type: Drug
intervention name: Pertuzumab
description: Participants will receive pertuzumab, administered by IV infusion on Day 1 of each 21-day cycle, at a loading dose of 840 mg for Cycle 1 and a dose of 420 mg for subsequent cycles, until disease progression or unacceptable toxicity.
arm group label: Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
last name: Reference Study ID Number: GO39374 https://forpatients.roche.com/
phone: 888-662-6728 (U.S. and Canada)
email: global-roche-genentech-trials@gene.com
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Completed
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: Canada
country: France
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Metformin
mesh term: Trastuzumab
mesh term: Pertuzumab
mesh term: Letrozole
mesh term: Fulvestrant
mesh term: Palbociclib
mesh term: Inavolisib