<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/NCT04423380</url>
  </required_header>
  <id_info>
    <org_study_id>SHC033-I-01</org_study_id>
    <nct_id>NCT04423380</nct_id>
  </id_info>
  <brief_title>A Study to Investigate Safety and Tolerability of SH3051 Capsule in Patients With Advanced Solid Tumors</brief_title>
  <official_title>A Phase I, Open-Label Study to Determine Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Efficacy of SH3051 Capsule in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanjing Sanhome Pharmaceutical, Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nanjing Sanhome Pharmaceutical, 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>
      The primary objective is to determine the safety profile of SH3051 in subjects with advanced&#xD;
      solid tumors. The second objective is to evaluate the PK profile and preliminary efficacy of&#xD;
      SH3051 solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase I, open-label study to assess the safety,tolerability, pharmacokinetics and&#xD;
      preliminary efficacy of SH3051 capsule, a small molecule inhibitor of type I transforming&#xD;
      growth factor-β(TGF-β) receptor serine/threonine kinase, in patients with advanced solid&#xD;
      tumors.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 14, 2020</start_date>
  <completion_date type="Anticipated">May 2021</completion_date>
  <primary_completion_date type="Anticipated">March 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose(MTD)</measure>
    <time_frame>Within the first 28 days of consecutive treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Dose Limiting Toxicity (DLT)</measure>
    <time_frame>Within the first 28 days of consecutive treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve(AUC)of SH3051</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half-life(T1/2)of SH3051</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum(or peak)concentration of SH3051</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate(ORR)</measure>
    <time_frame>up to 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival(PFS)</measure>
    <time_frame>up to 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rates(DCR）</measure>
    <time_frame>up to 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response(DOR)</measure>
    <time_frame>up to 12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Advanced Solid Tumor</condition>
  <arm_group>
    <arm_group_label>SH3051 capsules treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Twice Daily Administration of SH3051</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SH3051 capsule treatment</intervention_name>
    <description>Starting dose 20mg,oral administered twice daily.If tolerated subsequent cohorts will test increasing doses (40mg,60mg,80mg,100mg) of SH3051.</description>
    <arm_group_label>SH3051 capsules treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 18 and 70 years inclusive;&#xD;
&#xD;
          -  Histologically or cytologically confirmed advanced malignant solid tumors, eligible&#xD;
             patients have failed standard treatment, have no standard treatment, or are not&#xD;
             suitable for standard treatment at this stage as determined by the investigator.&#xD;
&#xD;
          -  Must have at least one evaluable lesion in dose escalation period and one&#xD;
             unidimensional measurable lesion according to RECIST version 1.1;&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;&#xD;
&#xD;
          -  Life expectancy ≥3 months;&#xD;
&#xD;
          -  Adequate hematological and biological function, confirmed by the following laboratory&#xD;
             values:ANC≥1.5×10^9/L;PLT≥75×10^9/L;Hb≥90g/L;TBIL≤1.5×ULN;AST and ALT≤3×ULN(ALT and&#xD;
             AST≤5×ULN for subjects with liver cancer or hepatic metastases);CLcr&gt;50&#xD;
             mL/min(according to Cockcroft-Gault);Child-Pugh score between 0~7 for subjects with&#xD;
             primary hepatic carcinoma;APTT≤1.5×ULN;INR≤1.5×ULN.&#xD;
&#xD;
          -  Men and women of childbearing potential are willing to employ an effective method of&#xD;
             contraception for the entire duration of study and 6 months after the last dose, and&#xD;
             female subjects of childbearing potential have a negative pregnancy test at baseline.&#xD;
&#xD;
          -  Provision of signed and dated, written informed consent prior to any study-specific&#xD;
             evaluation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment with any TGF-β inhibitors.&#xD;
&#xD;
          -  Anticancer treatment including radiation therapy, chemotherapy, hormonal therapy,&#xD;
             molecular targeted therapy, or immunotherapy within 4 weeks prior to the first dose of&#xD;
             SH3051(use of mitomycin or nitrosoureas within 6 weeks prior to the first dose;use of&#xD;
             oral oral fluorouracil and small molecule targeted drugs within 2 weeks ,or 5&#xD;
             half-lifes prior to the first dose;use of Chinese herbal anti-tumor treatment with 2&#xD;
             weeks prior to the first dose).&#xD;
&#xD;
          -  Have systematic hormonal therapy(prednisone&gt;20mg/d or similar drugs with equivalent&#xD;
             dose)or immunosuppressor therapy with 14 days prior to the first dose of study drug,&#xD;
             except using topical,ocular,intra-articular,intranasal,inhaled corticosteroids,and&#xD;
             preventive therapy using corticosteroids in short period(for instance,to prevent&#xD;
             hypersensitivity to contrast media).&#xD;
&#xD;
          -  Participate in other clinical trials within 4 weeks prior to study entry.&#xD;
&#xD;
          -  Concomitant use of any strong inhibitors or inducers of CYP3A4(except drug withdrawal&#xD;
             within one week prior to first dose of study drug).&#xD;
&#xD;
          -  History of allogeneic hematopoietic stem cell transplantation or organ&#xD;
             transplantation.&#xD;
&#xD;
          -  Adverse events occurred during previous anticancer therapy have not been recovered to&#xD;
             ≤1(CTCAE 5.0)except toxicity with no significant risk determined by investigators such&#xD;
             as alopecia.&#xD;
&#xD;
          -  Evidence of central nervous system (CNS) metastases accompanied with clinical&#xD;
             symptoms, or other evidence of uncontrolled CNS metastases Judged by investigators&#xD;
             that the patient should not participate in the study.&#xD;
&#xD;
          -  Presence of grade 3 or 4 gastrointestinal bleeding or esophageal and gastric varices.&#xD;
&#xD;
          -  Have moderate or severe cardiac disease, including but not limited to severe&#xD;
             arrhythmias or abnormal cardiac conduction, such as ventricular arrhythmias requiring&#xD;
             clinical intervention, degree II-III atrioventricular block,QTcF≥450 ms for male,&#xD;
             QTcF≥470 ms for female, or other structural heart disease with high risk as determined&#xD;
             by investigators;history of acute coronary syndrome, congestive heart failure,aortic&#xD;
             dissection,stroke or other≥grade 3 cardiovascular and cerebrovascular events within 6&#xD;
             months prior to the first dose of study drug;New York Heart Association (NYHA) Class&#xD;
             II or greater heart failure, or LVEF&lt;55%;cTnT or cTnI above the normal&#xD;
             limit;NT-proBNP&gt;1.25×ULN;uncontrolled hypertension;any risk factors to increase QTc or&#xD;
             arrhythmias, including heart failure,hypokalemia,congenital long QTc syndrome,family&#xD;
             history of long QT interval syndrome or history of unexplained sudden death occurred&#xD;
             in first degree relative less than 40 years of age, or using any concomitant&#xD;
             medication known to produce QTc prolongation.&#xD;
&#xD;
          -  Have active infection requiring systemic with one week prior to the first dose the&#xD;
             study drug.&#xD;
&#xD;
          -  Infection with hepatitis B virus(HBV)and hepatitis C virus(HCV) (volunteers with HBsAg&#xD;
             positive but HBV-DNA negative, or volunteers with HCV antibody positive but HCV-RNA&#xD;
             negative can be enrolled).&#xD;
&#xD;
          -  History of immune deficiency including HIV antibody positive.&#xD;
&#xD;
          -  Major surgery(not include biopsy),or significant traumatism,or requiring selective&#xD;
             operation within 4 weeks prior to study entry.&#xD;
&#xD;
          -  Inability to swallow the drug, or severe gastrointestinal disease affecting absorption&#xD;
             of the drug.&#xD;
&#xD;
          -  Uncontrolled effusion in the third space, not suitable for entry as determined by the&#xD;
             investigator.&#xD;
&#xD;
          -  With alcohol or drug abuse disorder.&#xD;
&#xD;
          -  With mental disorders or non-compliance.&#xD;
&#xD;
          -  Women who are pregnancy or breastfeeding.&#xD;
&#xD;
          -  Judgment by the investigator that the patient should not participate in the study.&#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_official>
    <last_name>Jin Li, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai East Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xian Shen</last_name>
    <phone>18651825172</phone>
    <email>shenxian@sanhome.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hongchan Zhang</last_name>
    <phone>15150516871</phone>
    <email>zhanghcyf@sanhome.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Shanghai East Hospital</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jin Li</last_name>
      <phone>13761222111</phone>
      <email>lijin@csso.org.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 7, 2020</last_update_submitted>
  <last_update_submitted_qc>June 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>advanced solid tumor</keyword>
  <keyword>TGF-β RI</keyword>
  <keyword>ALK5</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_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/NCT04423380
org study id: SHC033-I-01
nct id: NCT04423380
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The primary objective is to determine the safety profile of SH3051 in subjects with advanced
      solid tumors. The second objective is to evaluate the PK profile and preliminary efficacy of
      SH3051 solid tumors.
This is a phase I, open-label study to assess the safety,tolerability, pharmacokinetics and
      preliminary efficacy of SH3051 capsule, a small molecule inhibitor of type I transforming
      growth factor-β(TGF-β) receptor serine/threonine kinase, in patients with advanced solid
      tumors.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose(MTD)
time frame: Within the first 28 days of consecutive treatment
measure: Incidence of Dose Limiting Toxicity (DLT)
time frame: Within the first 28 days of consecutive treatment
measure: Area under the plasma concentration versus time curve(AUC)of SH3051
time frame: 4 weeks
measure: Elimination half-life(T1/2)of SH3051
time frame: 4 weeks
measure: Maximum(or peak)concentration of SH3051
time frame: 4 weeks
measure: Overall Response Rate(ORR)
time frame: up to 12 months
measure: Progression-free survival(PFS)
time frame: up to 12 months
measure: Disease control rates(DCR）
time frame: up to 12 months
measure: Duration of response(DOR)
time frame: up to 12 months
arm group label: SH3051 capsules treatment
arm group type: Experimental
description: Oral Twice Daily Administration of SH3051
intervention type: Drug
intervention name: SH3051 capsule treatment
description: Starting dose 20mg,oral administered twice daily.If tolerated subsequent cohorts will test increasing doses (40mg,60mg,80mg,100mg) of SH3051.
arm group label: SH3051 capsules treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jin Li, MD
role: Principal Investigator
affiliation: Shanghai East Hospital
last name: Xian Shen
phone: 18651825172
email: shenxian@sanhome.com
last name: Hongchan Zhang
phone: 15150516871
email: zhanghcyf@sanhome.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms