<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/NCT03791112</url>
  </required_header>
  <id_info>
    <org_study_id>BTP-66711</org_study_id>
    <nct_id>NCT03791112</nct_id>
  </id_info>
  <brief_title>A Phase I Study of BPI-16350 in Patients With Advanced Solid Tumor</brief_title>
  <official_title>A Phase I Study of BPI-16350 in Patients With Advanced Solid Tumor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Betta Pharmaceuticals Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Betta Pharmaceuticals Co., Ltd.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was an open-label Phase I study. The primary objective of the study was to assess&#xD;
      safety, tolerability, efficacy, and pharmacokinetic characteristics of BPI-16350 in different&#xD;
      dose groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study was divided into two sections: dose escalation section and expanded enrollment&#xD;
      section.&#xD;
&#xD;
      In dose escalation section, BPI-16350 were administered orally once daily (QD) to patients&#xD;
      with locally advanced or metastatic solid tumors in different dose levels.The study was&#xD;
      designed to evaluate the safety, tolerability, and pharmacokinetics of single dose and&#xD;
      multiple doses of BPI-16350.&#xD;
&#xD;
      In expanded enrollment section, based on the results of dose escalation section, BPI-16350&#xD;
      were administered orally to patients with locally advanced or metastatic solid tumors, to&#xD;
      further evaluate the safety, tolerability, and pharmacokinetics of BPI-16350.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 18, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Participants with Adverse Events</measure>
    <time_frame>24 months</time_frame>
    <description>The safety and tolerability variables include adverse events, physical examinations, vital signs , clinical laboratory evaluations including serum chemistry, hematology , and urinalysis, and electrocardiograms (ECGs) in triplicate,Incidence and nature of DLTs ( dose-limiting toxicity), To determine the MTD (maximum tolerated dose).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>1 month</time_frame>
    <description>Day 1-7 for single dose, and day 1-28 for steady state</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life time</measure>
    <time_frame>1 month</time_frame>
    <description>Day 1-7 for single dose, and day 1-28 for steady state</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>Time to Cmax</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>6-24 months</time_frame>
  </other_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">54</enrollment>
  <condition>Advanced Solid Cancer</condition>
  <arm_group>
    <arm_group_label>50mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 50 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>100mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 100 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>200mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 200 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>300mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 300 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>400mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 400 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>500mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 500 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BPI-16350</intervention_name>
    <description>BPI-16350 capsules administered orally</description>
    <arm_group_label>100mg QD</arm_group_label>
    <arm_group_label>200mg QD</arm_group_label>
    <arm_group_label>300mg QD</arm_group_label>
    <arm_group_label>400mg QD</arm_group_label>
    <arm_group_label>500mg QD</arm_group_label>
    <arm_group_label>50mg QD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histological or cytological diagnosis of patients with advanced solid tumors, pateints&#xD;
             couldn't be benefit from the existing standard treatment options, and patients were&#xD;
             not suitable for surgical resection or radiation therapy for the purpose of cure;&#xD;
&#xD;
          2. There were measurable lesions defined in RECIST v. 1.1. Tumor lesions that had&#xD;
             previously received radiotherapy or other local treatment were considered as&#xD;
             measurable lesions only when disease progression at the treatment site was clearly&#xD;
             recorded after treatment;&#xD;
&#xD;
          3. Age ≥ 18 and ≤ 70 years old;&#xD;
&#xD;
          4. Expected survival ≥ 12 weeks;&#xD;
&#xD;
          5. Eastern Cancer Cooperative Group (ECOG) performance status 0-1;&#xD;
&#xD;
          6. Adequate bone marrow, hepatic, and renal function;&#xD;
&#xD;
          7. Patients of child bearing potential must agree to take contraception during the study&#xD;
             and for 90 days after the last day of treatment;&#xD;
&#xD;
          8. All acute toxicity of previous anti-tumor treatment or surgery is relieved to baseline&#xD;
             severity or NCI CTCAE version 4.03 ≤ 1 (except for hair loss or other toxicity that&#xD;
             the investigator believes has no safety risk to the patient);&#xD;
&#xD;
          9. Voluntarily enroll and sign informed consent, follow the trial treatment plan and&#xD;
             visit plan.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Received other anti-tumor treatments (including chemotherapy, radiotherapy,&#xD;
             immunotherapy and experimental treatment) within 28 days (for myelosuppressive drugs&#xD;
             or treatment) or within 14 days (for non-myelosuppressive drugs or treatment) before&#xD;
             receiving the study drug;&#xD;
&#xD;
          2. Previous treatments for other CDK4/6 inhibitors, such as Abemaciclib (VERZENIOTM,&#xD;
             LY2835219), Palbociclib (IBRANCE®, PD0332991), Ribociclib (KISQALI®, LEE-011),&#xD;
             Birosiclib (XZP-) 3287), SHR-6390, Trilaciclib and G1T-38, etc.;&#xD;
&#xD;
          3. Any of the following cardiac criteria: unexplained or cardiovascular causes of&#xD;
             threatened syncope or syncope, ventricular tachycardia, ventricular fibrillation or&#xD;
             cardiac arrest. Corrected QT interval prolongation [A mean corrected QT interval (male&#xD;
             QTcF &gt; 450 msec or female QTcF &gt; 470 msec) obtained from 3 electrocardiogram (ECG)&#xD;
             examinations at rest. Various clinically significant cardiac rhythm, conduction,&#xD;
             resting ECG morphological abnormalities, such as complete left bundle branch block,&#xD;
             III degree block, II degree block, PR interval &gt; 250 msec;&#xD;
&#xD;
          4. Clinically active bacterial, fungal or viral infections (eg active hepatitis B (HBV),&#xD;
             hepatitis C (HCV), human immunodeficiency virus (HIV) and syphilis positive, no other&#xD;
             activities required at the time of enrollment Screening for sexual infections);&#xD;
&#xD;
          5. Patients who had undergone autologous or allogeneic organ or stem cell&#xD;
             transplantation; patients who had undergone major surgery or severe trauma within 4&#xD;
             weeks prior to the first dose;&#xD;
&#xD;
          6. The patient received the following treatment within 7 days prior to entering the&#xD;
             study: a known or potent CYP3A inhibitor or inducer, and a drug primarily metabolized&#xD;
             by CYP2C19; or consumed grapefruit and grapefruit juice;&#xD;
&#xD;
          7. Patients who received anti-tumor treatment of Chinese herbal medicine within 1 week&#xD;
             before the first dose;&#xD;
&#xD;
          8. There were primary CNS（central nervous system）malignant tumors. Patients with CNS&#xD;
             metastases who failed local treatment. For patients with asymptomatic brain&#xD;
             metastases, or stable clinical symptoms and no need for steroids and other treatments&#xD;
             for brain metastases ≥ 28 days can be enrolled;&#xD;
&#xD;
          9. Have had other malignant tumors in the past 5 years, except for basal cell carcinoma&#xD;
             and cervical carcinoma in situ after radical treatment;&#xD;
&#xD;
         10. Occurrence of venous/venous thrombosis within 6 months prior to the first dose, such&#xD;
             as cerebrovascular accidents (including transient ischemic attack, cerebral&#xD;
             hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;&#xD;
&#xD;
         11. The prevalence of familial and/or acquired thrombophilia, such as the presence of&#xD;
             genetic or acquired defects such as anticoagulant, coagulation factors, fibrinolytic&#xD;
             proteins, or the presence of acquired risk factors with a high tendency to&#xD;
             thromboembolism;&#xD;
&#xD;
         12. Any condition that affected the patient's swallowing of the drug, as well as&#xD;
             conditions that seriously affect the absorption or pharmacokinetic parameters of the&#xD;
             test drug, including uncontrollable nausea and vomiting, chronic gastrointestinal&#xD;
             disease, gastrointestinal resection or surgical history;&#xD;
&#xD;
         13. It was known to be severely allergic to study drugs or any excipients;&#xD;
&#xD;
         14. The existence of drugs of abuse and patients whose medical, psychological or social&#xD;
             conditions may interfere with or participate in the evaluation of the results of the&#xD;
             study;&#xD;
&#xD;
         15. Any unstable systemic diseases (including active ≥CTCAE level 2 clinically serious&#xD;
             infections, uncontrolled high blood pressure, unstable angina pectoris, congestive&#xD;
             heart failure, severe liver and kidney or metabolic diseases, etc.);&#xD;
&#xD;
         16. Any condition that was unstable or may jeopardize patient safety and its compliance&#xD;
             with the study;&#xD;
&#xD;
         17. Other conditions that the investigator believeed were not suitable for participation&#xD;
             in this trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Xichun XI Hu, Ph.D</last_name>
    <phone>13816110335</phone>
    <email>xchu2009@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Betta Pharmaceuticals Co.</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang Provice</state>
        <zip>311100</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jiaying Li, B.S.</last_name>
      <phone>0571-8926 3060</phone>
      <email>jiaying.li@bettapharma.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>December 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>June 15, 2022</last_update_submitted>
  <last_update_submitted_qc>June 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03791112
org study id: BTP-66711
nct id: NCT03791112
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This was an open-label Phase I study. The primary objective of the study was to assess
      safety, tolerability, efficacy, and pharmacokinetic characteristics of BPI-16350 in different
      dose groups.
The study was divided into two sections: dose escalation section and expanded enrollment
      section.

      In dose escalation section, BPI-16350 were administered orally once daily (QD) to patients
      with locally advanced or metastatic solid tumors in different dose levels.The study was
      designed to evaluate the safety, tolerability, and pharmacokinetics of single dose and
      multiple doses of BPI-16350.

      In expanded enrollment section, based on the results of dose escalation section, BPI-16350
      were administered orally to patients with locally advanced or metastatic solid tumors, to
      further evaluate the safety, tolerability, and pharmacokinetics of BPI-16350.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Participants with Adverse Events
time frame: 24 months
description: The safety and tolerability variables include adverse events, physical examinations, vital signs , clinical laboratory evaluations including serum chemistry, hematology , and urinalysis, and electrocardiograms (ECGs) in triplicate,Incidence and nature of DLTs ( dose-limiting toxicity), To determine the MTD (maximum tolerated dose).
measure: Cmax
time frame: 1 month
description: Day 1-7 for single dose, and day 1-28 for steady state
measure: Half-life time
time frame: 1 month
description: Day 1-7 for single dose, and day 1-28 for steady state
measure: Tmax
time frame: Time to Cmax
measure: Progression-free survival
time frame: 6-24 months
arm group label: 50mg QD
arm group type: Experimental
description: Participants received 50 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.
arm group label: 100mg QD
arm group type: Experimental
description: Participants received 100 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.
arm group label: 200mg QD
arm group type: Experimental
description: Participants received 200 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.
arm group label: 300mg QD
arm group type: Experimental
description: Participants received 300 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.
arm group label: 400mg QD
arm group type: Experimental
description: Participants received 400 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.
arm group label: 500mg QD
arm group type: Experimental
description: Participants received 500 mg BPI-16350 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 28 of a 28-day cycle.
intervention type: Drug
intervention name: BPI-16350
description: BPI-16350 capsules administered orally
arm group label: 100mg QD
arm group label: 200mg QD
arm group label: 300mg QD
arm group label: 400mg QD
arm group label: 500mg QD
arm group label: 50mg QD
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Xichun XI Hu, Ph.D
phone: 13816110335
email: xchu2009@hotmail.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
sharing ipd: Undecided