<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/NCT03827837</url>
  </required_header>
  <id_info>
    <org_study_id>SHR-1210-II-213</org_study_id>
    <nct_id>NCT03827837</nct_id>
  </id_info>
  <brief_title>Famitinib Plus Anti-PD1 Therapy for Advanced Urinary System Tumor, Advanced Gynecological Tumors</brief_title>
  <official_title>Famitinib Malate Plus Anti-PD1 Therapy (SHR-1210) in Advanced Renal Cell Carcinoma, Urothelial Carcinoma, Advanced Cervical Cancer, Relapse Ovarian Cancer, Endometrial Cancer: Multi-institutional, Open-label, Phase 2 Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu HengRui Medicine 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>
      Phase II multi-chort, adaptive two-stage, open label, nonrandomized study. The aim of our&#xD;
      study is to evaluate the efficacy and safety of anti-PD-1 antibody SHR-1210(Camrelizumab) in&#xD;
      combination with a small-molecule multikinase inhibitor Famitinib in subjects with advanced&#xD;
      RCC/UC/CC/EC and recurrent OC.&#xD;
&#xD;
      chort1: Renal Cell Carcinoma (RCC) chort2: Urothelial Carcinoma(UC) chort3: Ovarian Cancer&#xD;
      (OC) chort4: Cervical Cancer (CC) chort5: Endometrial Cancer (EC)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Stage 1: Approximately 110 participants will be recruited, 22 participants per chort; Stage&#xD;
      2: Approximately 55 participants will be recruited, 11 participants per chort, if more than&#xD;
      7（including 7） patients reached ORR in every chort ; Approximately 155 participants will be&#xD;
      recruited, 21 participants per chort, if 3 ≤ patients &lt;7 patients reached ORR in every chort.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 23, 2019</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 2</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>Overall response rate (ORR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Defined as complete or partial response per RECIST 1.1 criteria with assessment every 9 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Duration of Response (DoR) per RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Disease Control Rate per RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to objective response(TTR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Time to objective response per RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival(PFS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Progression-free survival(PFS) per RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival(OS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Overal Survial will be calculated based on Kaplan-Meier estimates</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>12-month survival rate</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>12-month survival rate will be calculated based on Kaplan-Meier estimates of Overall survival at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>number of participants who experience an adverse event (AE)</measure>
    <time_frame>From the first assignment of informed consent form up to 90 days after the last dose</time_frame>
    <description>number of participants who experience an adverse event (AE) per CTCAE 4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>serum SHR-1210 concentrations</measure>
    <time_frame>From the first dose up to 30 days after the last dose</time_frame>
    <description>serum SHR-1210 concentrations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positive rate of ADA</measure>
    <time_frame>From the first dose up to 30 days after the last dose</time_frame>
    <description>Positive rate of anti-SHR1210 antibody</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax)</measure>
    <time_frame>Day 1 of cycle 3 (each cycle is 21 days)</time_frame>
    <description>Cmax, based PK parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Observed Plasma Concentration (Tmax)</measure>
    <time_frame>Day 1 of cycle 3 (each cycle is 21 days)</time_frame>
    <description>Summarized by dose, cycle, day and time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Oral Clearance (CL/F)</measure>
    <time_frame>Day 1 of cycle 3 (each cycle is 21 days)</time_frame>
    <description>Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">265</enrollment>
  <condition>Renal Cell Carcinoma</condition>
  <condition>Urothelial Carcinoma</condition>
  <condition>Cervical Cancer</condition>
  <condition>Ovarian Cancer Recurrent</condition>
  <condition>Endometrial Cancer</condition>
  <arm_group>
    <arm_group_label>SHR-1210 combined with Famitinb</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SHR-1210 + Famitinib</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>SHR-1210</intervention_name>
    <description>SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody</description>
    <arm_group_label>SHR-1210 combined with Famitinb</arm_group_label>
    <other_name>Camrelizumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Famitinib</intervention_name>
    <description>a small-molecule multikinase inhibitor</description>
    <arm_group_label>SHR-1210 combined with Famitinb</arm_group_label>
    <other_name>Famitinib Malate Capsule</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Be willing and able to provide written informed consent/ for the trial.&#xD;
&#xD;
          2. Be at least 18 years of age on day of signing informed consent, male or female.&#xD;
&#xD;
          3. Patients with one of the following tumors:&#xD;
&#xD;
               -  Histologically or cytologically confirmed diagnosis of advanced renal cell&#xD;
                  carcinoma (defined as more than 50% clear cell component) after failure of IL-2&#xD;
                  and/or anti-VEGF TKI treatment. If patients didn't want to use anti-VEGF TKI&#xD;
                  medicine or couldn't stand anti-VEGF TKI medicine costs, they will also be&#xD;
                  considered.&#xD;
&#xD;
               -  Histologically or cytologically confirmed diagnosis of unresectable urothelial&#xD;
                  carcinoma of the renal pelvis, ureter, bladder, or urethra (defined as more than&#xD;
                  50% transitional cell component) after failure of no more than two prior&#xD;
                  platinum-based chemotherapeutic regimen.&#xD;
&#xD;
               -  Histologically or cytologically confirmed diagnosis of advanced squamous cell&#xD;
                  carcinoma of the cervix after failure of first-line system treatment.&#xD;
&#xD;
               -  Histologically confirmed diagnosis of recurrent or refractory epithelial ovarian&#xD;
                  cancer, fallopian tube cancer or primary peritoneal cancer that are relapsed and&#xD;
                  resistant (recurred less than 6 months after chemotherapy) or refractory&#xD;
                  (progressed on chemotherapy) to prior platinum-based standard care systemic&#xD;
                  regimen.&#xD;
&#xD;
               -  Histologically confirmed diagnosis of recurrent or refractory endometrial cancer&#xD;
                  that are relapsed and resistant or refractory (progressed on chemotherapy) to&#xD;
                  prior platinum-based standard care systemic regimen.&#xD;
&#xD;
          4. At least one measurable lesion according to RECIST 1.1.&#xD;
&#xD;
          5. The patients can swallow pills.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.&#xD;
&#xD;
          7. Life expectancy of at least 12 weeks.&#xD;
&#xD;
          8. The results of patients' blood tests are as follows:-Neutrophils≥1.5E+9/L; -&#xD;
             Plt≥90E+9/L; -Hb≥90g/L; -ALB≥30g/L ;-TSH≤1×ULN;-TBIL ≤ 1 ×ULN;-ALT and AST ≤ 3 ×ULN;&#xD;
             AKP≤ 2.5×ULN; -Creatinine ≤ 1.5×ULN.&#xD;
&#xD;
          9. Male or Female patient of childbearing potential (entering the study after a menstrual&#xD;
             period and who have a negative pregnancy test), who agrees to use two methods (one for&#xD;
             the patient and one for the partner) of medically acceptable forms of contraception&#xD;
             during the study and for 3 months after the last treatment intake.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with any active autoimmune disease or history of autoimmune disease,&#xD;
             including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis&#xD;
             (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism,&#xD;
             and hypothyroidism, except for subjects with vitiligo or resolved childhood&#xD;
             asthma/atopy. Asthma that requires intermittent use of bronchodilators or other&#xD;
             medical intervention should also be excluded.&#xD;
&#xD;
          2. Concurrent medical condition requiring the use of immunosuppressive medications, or&#xD;
             immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses &gt; 10&#xD;
             mg/day prednisone or equivalent are prohibited within 2 weeks before study drug&#xD;
             administration.&#xD;
&#xD;
          3. Known history of hypersensitivity to other antibody formulation.&#xD;
&#xD;
          4. Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Subjects with previously treated brain metastases may participate provided&#xD;
             they are stable (without evidence of progression by imaging for at least four weeks&#xD;
             prior to the first dose of trial treatment and any neurologic symptoms have returned&#xD;
             to baseline), have no evidence of new or enlarging brain metastases, and are not using&#xD;
             steroids for at least 2 weeks prior to trial treatment.&#xD;
&#xD;
          5. Hypertension and unable to be controlled within normal level following treatment of&#xD;
             anti-hypertension agents: systolic blood pressure ≥140 mmHg, diastolic blood pressure&#xD;
             ≥ 90 mmHg.&#xD;
&#xD;
          6. Clinically significant cardiovascular and cerebrovascular diseases, including but not&#xD;
             limited to（1）Congestive heart failure (New York heart association (NYHA) class &gt;&#xD;
             2)；（2）unstable or severe angina; （3）myocardial infarction within 12 months before&#xD;
             enrollment；（4） ventricular arrhythmia which need medical&#xD;
             intervention.（5）QTc&gt;450ms（male）/QTc&gt;470ms (female)；&#xD;
&#xD;
          7. Coagulation abnormalities (INR&gt;2.0、PT&gt;16s), with bleeding tendency or are receiving&#xD;
             thrombolytic or anticoagulant therapy.&#xD;
&#xD;
          8. Bleeding history, having bleeding event（≥3 Grade according CTCAE 4.0 ）within 4 weeks&#xD;
             before screening.&#xD;
&#xD;
          9. Tumor invasion around major vessels shown by imaging, high risk of major vascular&#xD;
             invasion leading to massive hemorrhage judged by investigators.&#xD;
&#xD;
         10. Previous Arterial/venous thrombosis events within 6 months.&#xD;
&#xD;
         11. Known hereditary or acquired bleeding and thrombosis tendency.&#xD;
&#xD;
         12. Proteinuria ≥ (++) and 24 hours total urine protein &gt; 1.0 g.&#xD;
&#xD;
         13. Prior chemotherapy, radiotherapy, surgery therapy within 4 weeks or palliative&#xD;
             radiotherapy within 2 weeks or target therapy within 5 half-life of the drug before&#xD;
             the study drug administration, or any unresolved AEs &gt; Common Terminology Criteria for&#xD;
             Adverse Events (CTCAE) Grade 1.&#xD;
&#xD;
         14. Active infection or an unexplained fever &gt; 38.5°C within 7 days before the study drug&#xD;
             administration, or baseline WBC&gt;15×E+9/L .&#xD;
&#xD;
         15. Has known history of Interstitial lung disease, or using steroids evidence of active,&#xD;
             non-infectious pneumonitis, or would interfere with the detection and handling of&#xD;
             suspicious drug-related pulmonary toxicity.&#xD;
&#xD;
         16. History of immunodeficiency or human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
         17. HBV DNA&gt;500 IU/ml，HCV RNA&gt;1000copies/ml，HBsAg+ and anti-HCV+；&#xD;
&#xD;
         18. Has a known additional malignancy within the last 5 years, or that is progressing or&#xD;
             requires active treatment. Exceptions include basal cell carcinoma of the skin that&#xD;
             has undergone potentially curative therapy or in situ cervical cancer or patients with&#xD;
             recurrent ovarian cancer has a known additional breast cancer that has been radical&#xD;
             mastectomy and doesn't relapse within 3 years.&#xD;
&#xD;
         19. Patients with treatment history of SHR-1210 or any other PD-L1 or PD-1 antagonists or&#xD;
             famitinib.&#xD;
&#xD;
         20. Patients who may receive live vaccine during the study, or previous had vaccination&#xD;
             within 4 weeks.&#xD;
&#xD;
         21. Any other medical, psychiatric, or social condition deemed by the investigator to be&#xD;
             likely to interfere with a subject's safety and participate in the study or would&#xD;
             interfere with the interpretation of the results or lead to the trial being terminated&#xD;
             early.&#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>Dingwei Ye, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Xiaohua Wu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Quanren Wang, MD</last_name>
    <phone>(+86) 021-50118402</phone>
    <email>wangquanren@hrglobe.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Huadong Hospital Affiliated to Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200136</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Director of urology</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>November 12, 2018</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>June 30, 2022</last_update_submitted>
  <last_update_submitted_qc>June 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2022</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>Carcinoma</mesh_term>
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
    <mesh_term>Endometrial Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Transitional Cell</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/NCT03827837
org study id: SHR-1210-II-213
nct id: NCT03827837
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Phase II multi-chort, adaptive two-stage, open label, nonrandomized study. The aim of our
      study is to evaluate the efficacy and safety of anti-PD-1 antibody SHR-1210(Camrelizumab) in
      combination with a small-molecule multikinase inhibitor Famitinib in subjects with advanced
      RCC/UC/CC/EC and recurrent OC.

      chort1: Renal Cell Carcinoma (RCC) chort2: Urothelial Carcinoma(UC) chort3: Ovarian Cancer
      (OC) chort4: Cervical Cancer (CC) chort5: Endometrial Cancer (EC)
Stage 1: Approximately 110 participants will be recruited, 22 participants per chort; Stage
      2: Approximately 55 participants will be recruited, 11 participants per chort, if more than
      7（including 7） patients reached ORR in every chort ; Approximately 155 participants will be
      recruited, 21 participants per chort, if 3 ≤ patients <7 patients reached ORR in every chort.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall response rate (ORR)
time frame: Up to 2 years
description: Defined as complete or partial response per RECIST 1.1 criteria with assessment every 9 weeks
measure: Duration of Response (DoR)
time frame: Up to 2 years
description: Duration of Response (DoR) per RECIST 1.1
measure: Disease Control Rate (DCR)
time frame: Up to 2 years
description: Disease Control Rate per RECIST 1.1
measure: Time to objective response(TTR)
time frame: Up to 2 years
description: Time to objective response per RECIST 1.1
measure: Progression-free survival(PFS)
time frame: Up to 2 years
description: Progression-free survival(PFS) per RECIST 1.1
measure: Overall survival(OS)
time frame: Up to 2 years
description: Overal Survial will be calculated based on Kaplan-Meier estimates
measure: 12-month survival rate
time frame: Up to 1 year
description: 12-month survival rate will be calculated based on Kaplan-Meier estimates of Overall survival at 12 months
measure: number of participants who experience an adverse event (AE)
time frame: From the first assignment of informed consent form up to 90 days after the last dose
description: number of participants who experience an adverse event (AE) per CTCAE 4.03
measure: serum SHR-1210 concentrations
time frame: From the first dose up to 30 days after the last dose
description: serum SHR-1210 concentrations
measure: Positive rate of ADA
time frame: From the first dose up to 30 days after the last dose
description: Positive rate of anti-SHR1210 antibody
measure: Maximum Observed Plasma Concentration (Cmax)
time frame: Day 1 of cycle 3 (each cycle is 21 days)
description: Cmax, based PK parameters
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
time frame: Day 1 of cycle 3 (each cycle is 21 days)
description: Summarized by dose, cycle, day and time
measure: Apparent Oral Clearance (CL/F)
time frame: Day 1 of cycle 3 (each cycle is 21 days)
description: Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
arm group label: SHR-1210 combined with Famitinb
arm group type: Experimental
description: SHR-1210 + Famitinib
intervention type: Biological
intervention name: SHR-1210
description: SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody
arm group label: SHR-1210 combined with Famitinb
other name: Camrelizumab
intervention type: Drug
intervention name: Famitinib
description: a small-molecule multikinase inhibitor
arm group label: SHR-1210 combined with Famitinb
other name: Famitinib Malate Capsule
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dingwei Ye, MD
role: Principal Investigator
affiliation: Fudan University
last name: Xiaohua Wu, MD
role: Principal Investigator
affiliation: Fudan University
last name: Quanren Wang, MD
phone: (+86) 021-50118402
email: wangquanren@hrglobe.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Uterine Cervical Neoplasms
mesh term: Carcinoma, Renal Cell
mesh term: Endometrial Neoplasms
mesh term: Carcinoma, Transitional Cell