<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/NCT02993913</url>
  </required_header>
  <id_info>
    <org_study_id>ACE-CT-006I</org_study_id>
    <nct_id>NCT02993913</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability and Pharmacokinetics of Simmiparib in Patients With Malignant Advanced Solid Tumor</brief_title>
  <official_title>A Safety, Tolerability and Pharmacokinetic Study of Single and Repeat Oral Escalating Doses of Simmiparib in Patients With Advanced Malignant Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Acebright Pharmaceuticals Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Acebright Pharmaceuticals Co., Ltd.</source>
  <brief_summary>
    <textblock>
      Phase I dose escalating trial. Primary objectives of this study are to assess the safety and&#xD;
      tolerability of Simmiparib following single and multiple oral doses in patients with advanced&#xD;
      solid malignancies, to determine the maximum tolerance dose (MTD) and dose limiting toxicity&#xD;
      (DLT), and pharmacokinetic profile.&#xD;
&#xD;
      The Secondary objective is to observe the preliminary antitumor effect of Simmiparib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This single-center, nonrandomized, open-label, dose-escalating study. The trial was divided&#xD;
      into dose escalation and expansion stages.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>Per doselevel of 3 to 6 patients (When 3-6 patients have completed DLT periods of 4 weeks)</time_frame>
    <description>The Dose level at which more than 1/6 patients develop a Dose Limiting Toxicity (DLT)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Cmax (maximum concentration)</measure>
    <time_frame>At day 1 single dose period, day 8 and 28 multiple dose period day</time_frame>
    <description>PK blood collection Before 0:00h and after 0.25h、0.50h、1:00h、1.50h、2:00h、3:00h、4:00h、6:00h、8:00h、10:00h、24:00h、48:00h、72:00h at single dose period.&#xD;
PK blood collection before 0:00h and after 0.25h、0.50、1:00h、1.50h、2:00h、3:00h、4:00h、6:00h、8:00h、10:00h and 12:00h at multiple dose period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Tmax (Time of maximum concentration)</measure>
    <time_frame>At day 1 single dose period, day 8 and 28 multiple dose period day</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics AUC (Area Under the Curve)</measure>
    <time_frame>At day 1 single dose period, day 8 and 28 multiple dose period day</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Poly ADP-ribose polymerase (PARP) inhibition measured by PAR assay</measure>
    <time_frame>Up to 4 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Up to 4 months</time_frame>
    <description>ORR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Malignant Advanced Solid Tumor</condition>
  <arm_group>
    <arm_group_label>Simmiparib tablet monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: Simmiparib tablet oral Qd or Bid</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Simmiparib</intervention_name>
    <description>Simmiparib Tablets, oral administration</description>
    <arm_group_label>Simmiparib tablet monotherapy</arm_group_label>
    <other_name>SMOCL-9112</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients confirmed with advanced solid tumor based on pathology and/or cytology,&#xD;
             considered unresponsive or poorly responsive to standard therapies, no curative&#xD;
             therapies or can't tolerate standard therapies;&#xD;
&#xD;
          2. Patients must have measurable disease in accordance with RECIST criteria v. 1.1, at&#xD;
             least one lesion that can be accurately measured in CT and MRI at least one dimension&#xD;
             ( longest diameter≥10mm; if lymph node, short diameter≥15mm );&#xD;
&#xD;
          3. Age≥18 and ≤75 years, both men and women, no history of drug abuse and alcohol;&#xD;
&#xD;
          4. Life expectancy≥ 3 months and can be followed for safety and efficiency&#xD;
&#xD;
          5. Received no prior anti-tumor therapies at least within past 4 weeks and no other&#xD;
             adjuvant anti-tumor regimen(including steroids mediations )&#xD;
&#xD;
          6. Have recovered to≤ common terminology criteria of adverse events (CTC-AE) 1 from&#xD;
             toxicities of prior therapy&#xD;
&#xD;
          7. Not participated in any clinical trials within 28 days;&#xD;
&#xD;
          8. Not have received treatment of poly-ADP ribose polymerase (PARP) inhibitor;&#xD;
&#xD;
          9. No serious abnormal hematopoiesis function, has adequate cardiac, pulmonic, hepatic&#xD;
             and renal function. Blood routine and blood biochemical examination within 2 weeks&#xD;
             before enrollment : White blood cell (WBC) ≥4000/mm3, Absolute neutrophil count (ANC)&#xD;
             ≥1,500/mm3, Platelets ≥100,000/mm3, Coagulation function ≤ 1.5 times upper limit of&#xD;
             normal (ULN), serum creatinine ≤ 1.5 times ULN, Total bilirubin ≤ 1.5 times ULN,&#xD;
             Patients without liver metastasis, Aspartate aminotransferase (AST)/alanine&#xD;
             aminotransferase (ALT)≤ 2.5 times ULN; Patients with liver metastasis, Aspartate&#xD;
             aminotransferase (AST)/alanine aminotransferase (ALT)/≤ 2.5 times ULN, NYHAclass≤Ⅱand&#xD;
             Left ventricular ejection fraction ( LVEF)&gt;50%;&#xD;
&#xD;
         10. Virology test: negative HbsAg, HCV, HIV and syphilis&#xD;
&#xD;
         11. Eastern Cooperative Oncology Group(ECOG) performance status ≤2;&#xD;
&#xD;
         12. No history of other malignant tumors, except cervical carcinoma in situ, basal skin&#xD;
             cancer or squamous-cell carcinoma that have been cured; No other serious illnesses&#xD;
             that are in conflict with this study and significant heart disease and psychosis;&#xD;
&#xD;
         13. Ability to understand and a willingness to sign a written informed consent; Obtaining&#xD;
             consent before any operation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with serious medical disease, including, severe cardiopathy, vascular&#xD;
             disease, uncontrolled diabetes, uncontrolled hypertension, severe infection , or&#xD;
             psychosis, etc.;&#xD;
&#xD;
          2. Patients with primary brain lesion or metastases lesion;&#xD;
&#xD;
          3. Female patient who is pregnant, breast feeding or unwilling to contraception;&#xD;
&#xD;
          4. Patient who received or is receiving any other investigational agents within 4 weeks&#xD;
             prior to treatment;&#xD;
&#xD;
          5. Patients, with poor compliance, or based on the opinion of the investigator, should&#xD;
             not be enrolled into this study;&#xD;
&#xD;
          6. has not recovered to grade 1 or better from any adverse events related to previous&#xD;
             therapy.&#xD;
&#xD;
          7. Neurotoxicity observed in previous antineoplastic therapy has not recovered to grade 1&#xD;
             or below.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xichun Hu</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>MohammadAbdul Kaium</last_name>
    <phone>0086-21-51323300</phone>
    <phone_ext>4080</phone_ext>
    <email>kaium@acebright.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jian Liu</last_name>
    <phone>0086-21-51323300</phone>
    <email>jian.liu@acebright.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xichun Hu, Ph.D.</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>January 3, 2017</last_update_submitted>
  <last_update_submitted_qc>January 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT02993913
org study id: ACE-CT-006I
nct id: NCT02993913
lead sponsor: 
Phase I dose escalating trial. Primary objectives of this study are to assess the safety and
      tolerability of Simmiparib following single and multiple oral doses in patients with advanced
      solid malignancies, to determine the maximum tolerance dose (MTD) and dose limiting toxicity
      (DLT), and pharmacokinetic profile.

      The Secondary objective is to observe the preliminary antitumor effect of Simmiparib.
This single-center, nonrandomized, open-label, dose-escalating study. The trial was divided
      into dose escalation and expansion stages.
allocation: N/A
intervention model: Single Group Assignment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: Per doselevel of 3 to 6 patients (When 3-6 patients have completed DLT periods of 4 weeks)
description: The Dose level at which more than 1/6 patients develop a Dose Limiting Toxicity (DLT)
measure: Pharmacokinetic Cmax (maximum concentration)
time frame: At day 1 single dose period, day 8 and 28 multiple dose period day
description: PK blood collection Before 0:00h and after 0.25h、0.50h、1:00h、1.50h、2:00h、3:00h、4:00h、6:00h、8:00h、10:00h、24:00h、48:00h、72:00h at single dose period.
PK blood collection before 0:00h and after 0.25h、0.50、1:00h、1.50h、2:00h、3:00h、4:00h、6:00h、8:00h、10:00h and 12:00h at multiple dose period
measure: Pharmacokinetic Tmax (Time of maximum concentration)
time frame: At day 1 single dose period, day 8 and 28 multiple dose period day
measure: Pharmacokinetics AUC (Area Under the Curve)
time frame: At day 1 single dose period, day 8 and 28 multiple dose period day
measure: Poly ADP-ribose polymerase (PARP) inhibition measured by PAR assay
time frame: Up to 4 months
measure: Overall Response Rate (ORR)
time frame: Up to 4 months
description: ORR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
arm group label: Simmiparib tablet monotherapy
arm group type: Experimental
description: Drug: Simmiparib tablet oral Qd or Bid
intervention type: Drug
intervention name: Simmiparib
description: Simmiparib Tablets, oral administration
arm group label: Simmiparib tablet monotherapy
other name: SMOCL-9112
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Xichun Hu
role: Principal Investigator
affiliation: Fudan University
last name: MohammadAbdul Kaium
phone: 0086-21-51323300
phone ext: 4080
email: kaium@acebright.com
last name: Jian Liu
phone: 0086-21-51323300
email: jian.liu@acebright.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor