<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/NCT03826589</url>
  </required_header>
  <id_info>
    <org_study_id>WI224183 / UW 18-417</org_study_id>
    <nct_id>NCT03826589</nct_id>
  </id_info>
  <brief_title>Avelumab With Axitinib in Persistent or Recurrent Cervical Cancer After Platinum-based Chemotherapy</brief_title>
  <acronym>ALARICE</acronym>
  <official_title>Avelumab With Axitinib in Persistent or Recurrent Cervical Cancer After Platinum-based Chemotherapy - a Proof-of-concept Study (ALARICE Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Hong Kong</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-arm, Simon's 2-stage, proof-of-concept trial. The aim is to evaluate the&#xD;
      efficacy and safety of avelumab with axitinib in patients with persistent or recurrent&#xD;
      cervical cancer following platinum-based chemotherapy. The study hypothesis is that the&#xD;
      combination of avelumab and axitinib can significantly improve the objective response rate&#xD;
      (ORR) with acceptable toxicity compared to traditional chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cervical cancer is the fourth commonest female cancer in the world. When there is distant&#xD;
      metastasis or recurrence, platinum-based chemotherapy is the usual treatment option. Once&#xD;
      this first-line chemotherapy fails, the prognosis is dismal. Various second-line agents&#xD;
      including second-line chemotherapy agents and immune checkpoint inhibitors have&#xD;
      unsatisfactory response rate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2019</start_date>
  <completion_date type="Anticipated">July 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 1, 2024</primary_completion_date>
  <phase>N/A</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>Objective response rate (ORR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>ORR is defined as the proportion of patients who have a CR or PR to the study drugs.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The time from first dose of trial medication to first documentation of objective tumor progression (PD) or to death due to any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Overall survival is defined as the time from first dose of trial medication to date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective tumor response rate</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Objective tumor response rate according to the immune-related ResponseCriteria Derived from RECIST 1.1 (irRECIST)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate at 12 weeks</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Disease control rate at 12 weeks including complete response (CR), partial response (PR), stable disease (SD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Duration of response and duration of clinical benefit including CR, PR and SD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of abnormal laboratory values and/or adverse events that are related to the treatment drugs</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Treatment-related adverse events classified by CTCAE version 5.0 and laboratory safety assessments</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">23</enrollment>
  <condition>Cervical Cancer</condition>
  <arm_group>
    <arm_group_label>Avelumab and Axitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Avelumab: IV treatment; administered at 10 mg/kg IV every two weeks in a 4-weekly cycle up to 12 cycles or until disease progression or intolerable side effects (whichever occurs first)&#xD;
Axitinib: Oral treatment; administered at 5 mg PO BID in a 4-weekly cycle up to 12 cycles or until disease progression or intolerable side effects (whichever occurs first)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Avelumab</intervention_name>
    <description>an anti-programmed cell death ligand 1</description>
    <arm_group_label>Avelumab and Axitinib</arm_group_label>
    <other_name>Bavencio</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Axitinib</intervention_name>
    <description>a tyrosine kinase inhibitor that also inhibits VEGF receptor 1-3, c-KIT and PDGFR</description>
    <arm_group_label>Avelumab and Axitinib</arm_group_label>
    <other_name>Inlyta</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must be at least 18 years old.&#xD;
&#xD;
          2. Patients must have histologically confirmed cervical cancer, either squamous cell,&#xD;
             adenocarcinoma or adenosquamous, that is either persistent or recurrent after at least&#xD;
             one prior course of platinum-based chemotherapy. The platinum used in concurrent&#xD;
             chemo-irradiation is not counted.&#xD;
&#xD;
          3. Patients should not be amenable to further surgery or radiotherapy except for the&#xD;
             purpose of symptomatic relief.&#xD;
&#xD;
          4. Patients should have ECOG performance score 0 to 2.&#xD;
&#xD;
          5. Patients must have at least one target lesion by the RECIST 1.1 criteria.&#xD;
&#xD;
          6. Prior chemotherapy must have been completed at least 3 weeks before study drug&#xD;
             administration, and all AEs have either returned to baseline or stabilized.&#xD;
&#xD;
          7. Prior systemic radiation therapy must have been completed at least 4 weeks before&#xD;
             study drug administration. Prior focal radiotherapy must have completed at least 2&#xD;
             weeks before study drug administration.&#xD;
&#xD;
          8. Patients must have recovered from any major surgery that has been done at least 4&#xD;
             weeks before study drug administration.&#xD;
&#xD;
          9. Patients must have adequate bone marrow, renal, hepatic, thyroid and neurological&#xD;
             function.&#xD;
&#xD;
         10. Patients should be willing to have blood tests where the blood will be used for&#xD;
             biomarker studies.&#xD;
&#xD;
         11. Formalin-fixed, paraffin-embedded (FFPE) archival tumor specimens of the primary&#xD;
             tumors, should be available during screening. Alternatively, 15 unstained slides (6&#xD;
             minimum) will be acceptable.&#xD;
&#xD;
         12. Patients should agree for de novo biopsy if the tumors are at the cervix or vagina, or&#xD;
             any other sites that are easy and safe to be biopsied. Tumors will be used for&#xD;
             biomarker studies.&#xD;
&#xD;
         13. Patients who have childbearing potential should practice highly effective&#xD;
             contraception throughout the study until at least 30 days after completion of the&#xD;
             treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with concurrent malignancy within five years (except for basal or squamous&#xD;
             cell skin cancer or in-situ breast cancer) are excluded.&#xD;
&#xD;
          2. Patients who have history of autoimmune diseases or other diseases requiring systemic&#xD;
             steroid are excluded.&#xD;
&#xD;
             Patients with vitiligo, type I diabetes mellitus, resolved asthma or atopy, stable&#xD;
             autoimmune thyroid disease, eczema, psoriasis not requiring systemic treatment*, or&#xD;
             not expected to recur in the absence of an external trigger are permitted to enroll.&#xD;
&#xD;
          3. Patients with the following past significant medical history in the last six months&#xD;
             are excluded, such as pneumonitis, active or chronic viral hepatitis, cirrhosis, and&#xD;
             inherited liver disease, myocardial infarction, unstable angina, unstable cardiac&#xD;
             arrhythmia or clinically significant valvular heart diseases, CTCAE Grade 2 or greater&#xD;
             peripheral vascular disease, active brain metastases or leptomeningeal metastases,&#xD;
             uncontrolled seizures, subarachnoid hemorrhage, thromboembolic events.&#xD;
&#xD;
          4. Patients with a condition requiring systemic treatment with either corticosteroids (&gt;&#xD;
             10 mg daily prednisone or equivalents) or other immunosuppressive medications within&#xD;
             14 days of the start of treatment are excluded. Inhaled, local or topical steroids,&#xD;
             systemic corticosteroids at physiologic doses, steroid used as pre-medication are&#xD;
             allowed.&#xD;
&#xD;
          5. Patients with severe gastrointestinal conditions such as evidence of bowel obstruction&#xD;
             or uncontrolled diarrhea in the last 4 weeks prior to enrollment, or history of&#xD;
             inflammatory bowel disease, are not eligible.&#xD;
&#xD;
          6. Patients with uncontrolled hypertension (systolic &gt;160mmHg or diastolic &gt; 110mmHg)&#xD;
             despite medication, active bleeding, bone fracture, unhealed wounds, clinically&#xD;
             significant proteinuria (&gt; 2g of protein over 24 hours), are excluded.&#xD;
&#xD;
          7. Patients with unhealed wounds include abdominal or pelvic fistula, gastrointestinal&#xD;
             perforation or intra-abdominal abscess are excluded.&#xD;
&#xD;
          8. Patients having had severe infections within 4 weeks prior to the start of treatment,&#xD;
             including, but not limited to, hospitalization for complications of infection,&#xD;
             bacteremia, or severe pneumonia, and those who have active infection requiring&#xD;
             systematic treatment, are excluded.&#xD;
&#xD;
          9. Patents with active tuberculosis, history of positive test for human immunodeficiency&#xD;
             virus (HIV) or known acquired immunodeficiency syndrome (AIDS) are excluded.&#xD;
&#xD;
         10. Patients who have suicidal ideations or behaviors requiring psychiatric intervention&#xD;
             within 3 months prior to the start of treatment are excluded.&#xD;
&#xD;
         11. Patients who have history of severe (CTCAE Grade 3 or above) hypersensitivity reaction&#xD;
             to any investigational products or any component in its formulations, and any&#xD;
             monoclonal antibody, are excluded.&#xD;
&#xD;
         12. Patients who have known hypersensitivity or allergy to biopharmaceuticals produced in&#xD;
             Chinese hamster ovary cells or any component of the avelumab formulation.&#xD;
&#xD;
         13. Patients who have persisting toxicities related to previous therapy (NCI CTCAE v 5.0&#xD;
             Grade &gt;1) are excluded. However, alopecia, Grade 2 or less sensory neuropathy, or&#xD;
             other toxicities of Grade 2 or below that do not constitute a safety risk according to&#xD;
             the investigators' judgment, are allowed.&#xD;
&#xD;
         14. Patients who have received prior immunotherapy, such as anti-PD-1, anti-PD-L1,&#xD;
             anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting&#xD;
             T-cell co-stimulation or immune checkpoint pathways, are excluded.&#xD;
&#xD;
         15. Patients who have received axitinib before are excluded.&#xD;
&#xD;
         16. Patients who received other anti-angiogenics within the last 6 months are excluded.&#xD;
&#xD;
         17. Patients with prior allogeneic stem cell or solid organ transplantation are excluded.&#xD;
&#xD;
         18. Use of other investigational drugs (drugs not marketed for any indication) within 28&#xD;
             days or at least 5 half-lives (whichever is longer) before the start of treatment, or&#xD;
             during the course of this trial, is not allowed.&#xD;
&#xD;
         19. Use of any live attenuated vaccines against infectious diseases (e.g. influenza,&#xD;
             varicella, etc.) within 4 weeks (28 days) of the start of treatment and during the&#xD;
             study therapy is not allowed.&#xD;
&#xD;
         20. Patients with major operation within 28 days or open biopsy within 7 days before&#xD;
             enrolment are not eligible.&#xD;
&#xD;
         21. Patients planned to have major surgery during the course of the study are excluded.&#xD;
&#xD;
         22. Patients who are pregnant or breastfeeding are excluded.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ka Yu Tse</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Hong Kong</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ka Yu Tse</last_name>
    <phone>852-22554518</phone>
    <email>tseky@hku.hk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tina Wei</last_name>
    <phone>852-22554265</phone>
    <email>tinawei@hku.hk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The University of Hong Kong</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ka Yu Tse</last_name>
      <phone>852-22554518</phone>
      <email>tseky@hku.hk</email>
    </contact>
    <contact_backup>
      <last_name>Lesley Lau</last_name>
      <phone>852-22554265</phone>
      <email>lsk382@hku.hk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>February 23, 2022</last_update_submitted>
  <last_update_submitted_qc>February 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Dr. Ka-Yu Tse</investigator_full_name>
    <investigator_title>Clinical Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Cervical cancer</keyword>
  <keyword>Avelumab</keyword>
  <keyword>Axitinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Avelumab</mesh_term>
    <mesh_term>Axitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Undecided</ipd_description>
  </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/NCT03826589
org study id: WI224183 / UW 18-417
nct id: NCT03826589
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a single-arm, Simon's 2-stage, proof-of-concept trial. The aim is to evaluate the
      efficacy and safety of avelumab with axitinib in patients with persistent or recurrent
      cervical cancer following platinum-based chemotherapy. The study hypothesis is that the
      combination of avelumab and axitinib can significantly improve the objective response rate
      (ORR) with acceptable toxicity compared to traditional chemotherapy.
Cervical cancer is the fourth commonest female cancer in the world. When there is distant
      metastasis or recurrence, platinum-based chemotherapy is the usual treatment option. Once
      this first-line chemotherapy fails, the prognosis is dismal. Various second-line agents
      including second-line chemotherapy agents and immune checkpoint inhibitors have
      unsatisfactory response rate.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: Up to 2 years
description: ORR is defined as the proportion of patients who have a CR or PR to the study drugs.
measure: Progression-free survival (PFS)
time frame: Up to 2 years
description: The time from first dose of trial medication to first documentation of objective tumor progression (PD) or to death due to any cause, whichever occurs first.
measure: Overall survival
time frame: Up to 2 years
description: Overall survival is defined as the time from first dose of trial medication to date of death due to any cause.
measure: Objective tumor response rate
time frame: Up to 2 years
description: Objective tumor response rate according to the immune-related ResponseCriteria Derived from RECIST 1.1 (irRECIST)
measure: Disease control rate at 12 weeks
time frame: Up to 2 years
description: Disease control rate at 12 weeks including complete response (CR), partial response (PR), stable disease (SD)
measure: Duration of response
time frame: Up to 2 years
description: Duration of response and duration of clinical benefit including CR, PR and SD
measure: Rates of abnormal laboratory values and/or adverse events that are related to the treatment drugs
time frame: Up to 2 years
description: Treatment-related adverse events classified by CTCAE version 5.0 and laboratory safety assessments
arm group label: Avelumab and Axitinib
arm group type: Experimental
description: Avelumab: IV treatment; administered at 10 mg/kg IV every two weeks in a 4-weekly cycle up to 12 cycles or until disease progression or intolerable side effects (whichever occurs first)
Axitinib: Oral treatment; administered at 5 mg PO BID in a 4-weekly cycle up to 12 cycles or until disease progression or intolerable side effects (whichever occurs first)
intervention type: Drug
intervention name: Avelumab
description: an anti-programmed cell death ligand 1
arm group label: Avelumab and Axitinib
other name: Bavencio
intervention type: Drug
intervention name: Axitinib
description: a tyrosine kinase inhibitor that also inhibits VEGF receptor 1-3, c-KIT and PDGFR
arm group label: Avelumab and Axitinib
other name: Inlyta
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ka Yu Tse
role: Principal Investigator
affiliation: The University of Hong Kong
last name: Ka Yu Tse
phone: 852-22554518
email: tseky@hku.hk
last name: Tina Wei
phone: 852-22554265
email: tinawei@hku.hk
facility: 
status: Recruiting
contact: 
contact backup: 
country: Hong Kong
responsible party type: Principal Investigator
investigator affiliation: The University of Hong Kong
investigator full name: Dr. Ka-Yu Tse
investigator title: Clinical Associate Professor
mesh term: Uterine Cervical Neoplasms
mesh term: Avelumab
mesh term: Axitinib
sharing ipd: Undecided
ipd description: Undecided