xml: <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/NCT05983237</url>
    </required_header>
    <id_info>
      <org_study_id>MA-MM-Ⅱ-005</org_study_id>
      <nct_id>NCT05983237</nct_id>
    </id_info>
    <brief_title>Fluzoparib in Combination With Camrelizumab and Temozolomide in Advanced Melanoma</brief_title>
    <official_title>Phase Ib Study of Fluzoparib in Combination With Camrelizumab and Temozolomide in Advanced Melanoma With Homologous Recombination (HR) Mutation ，a Single-center Open-label Exploratory Clinical Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Jun Guo</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Peking University Cancer Hospital &amp; Institute</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to evaluate how well fuzoparib in combination with camrelizumab&#xD;
        and temozolomide works in treating patients with advanced, metastatic melanoma with the&#xD;
        homologous recombination (HR) pathway gene mutation / alteration.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Treatment with PARP inhibitors could represent a novel opportunity to selectively kill a&#xD;
        subset of cancer cells with deficiencies in DNA repair pathways. Non-BRCA deficiencies in&#xD;
        homologous recombination DNA repair genes could also enhance tumor cell sensitivity to PARP&#xD;
        inhibitors. Therefore, PARP inhibitors are also selectively cytotoxic for cancer cells with&#xD;
        deficiencies in DNA repair proteins other than BRCA1 and BRCA2.&#xD;
  &#xD;
        In melanoma, genetic HR mutation/ alterations are rather common. Retrospective data showed&#xD;
        that nearly18-40% of melanoma harbors a mutation in at least 1 of the HR genes in their&#xD;
        tumor. The commonly altered genes were ARID1A, FANCA, ATM, BRCA1, ATRX and BRCA2, ATR, BRCA1&#xD;
        BRIP1 and SF3B1. These findings indicate that HR mutations / alterations are frequently&#xD;
        observed in metastatic melanoma, and they suggest that PARP inhibitors could potentially be&#xD;
        of a great clinical value in a substantial portion of the patients with advanced melanoma.&#xD;
  &#xD;
        In this clinical study, clinical efficacy of fluzoparib in combination with camrelizumab and&#xD;
        temozolomide will be evaluated by assessing an objective clinical response rate in patients&#xD;
        with advanced, metastatic melanoma with the homologous recombination (HR) pathway gene&#xD;
        mutation / alteration.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 31, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <phase>Phase 1/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>Objective Response Rate (ORR)</measure>
      <time_frame>6 months</time_frame>
      <description>ORR of Fluzoparib in combination with Camrelizumab and Temozolomide in patients with advanced melanoma with genetic homologous recombination (HR) mutation/ alteration using RECIST v1.1</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Melanoma</condition>
    <arm_group>
      <arm_group_label>Camre+Fluzo+TMZ</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>This arm will enroll patients who has advanced melanoma with a genetic HR mutation/ alteration .</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fluzoparib Camrelizumab Temozolomide</intervention_name>
      <description>Fluzoparib 50-150mg bid po, d1-21, q3w Camrelizumab 200mg iv, d1, q3w Temozolomide 50mg/m2-200mg/m2 d1-5,q3w</description>
      <arm_group_label>Camre+Fluzo+TMZ</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Histologically confirmed diagnosis of unresectable or metastatic stage III or IV&#xD;
               melanoma;&#xD;
  &#xD;
            2. Must have genetic HR and/or SF3B1 mutation/ alteration;&#xD;
  &#xD;
            3. Must have measurable disease based on RECIST 1.1;&#xD;
  &#xD;
            4. Must have an ECOG performance status of 0 to 1;&#xD;
  &#xD;
            5. Must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline;&#xD;
  &#xD;
            6. Anticipated overall survival more than 3 months;&#xD;
  &#xD;
            7. Male and no pregnant female, able to adapt birth control methods during treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Previously treated with a PARP inhibitor;&#xD;
  &#xD;
            2. Hypersensitivity to Fluzoparib or Camrelizumab or Temozolomide;&#xD;
  &#xD;
            3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
               (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
               immunosuppressive therapy within 7 days prior to the first dose of study drug;&#xD;
  &#xD;
            4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
               (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
               immunosuppressive therapy within 7 days prior to the first dose of study drug;&#xD;
  &#xD;
            5. Patients with a history of other (including unknown primary) malignancies within 5&#xD;
               years prior to the first dose of trial treatment;&#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>Jun Guo</last_name>
      <role>Study Director</role>
      <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jun Guo</last_name>
      <phone>86-10-88121122</phone>
      <email>guoj307@126.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Bin Lian</last_name>
      <phone>86-10-88121122</phone>
      <email>lianbin0214@126.com</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 9, 2023</last_update_submitted>
    <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Peking University Cancer Hospital &amp; Institute</investigator_affiliation>
      <investigator_full_name>Jun Guo</investigator_full_name>
      <investigator_title>Director</investigator_title>
    </responsible_party>
    <keyword>Homologous recombination (HR)</keyword>
    <keyword>PARP inhibitor</keyword>
    <keyword>anti PD-1 antibody</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Melanoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Temozolomide</mesh_term>
      <mesh_term>Fluzoparib</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05983237
  org study id: MA-MM-Ⅱ-005
  nct id: NCT05983237
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this study is to evaluate how well fuzoparib in combination with camrelizumab
        and temozolomide works in treating patients with advanced, metastatic melanoma with the
        homologous recombination (HR) pathway gene mutation / alteration.
  Treatment with PARP inhibitors could represent a novel opportunity to selectively kill a
        subset of cancer cells with deficiencies in DNA repair pathways. Non-BRCA deficiencies in
        homologous recombination DNA repair genes could also enhance tumor cell sensitivity to PARP
        inhibitors. Therefore, PARP inhibitors are also selectively cytotoxic for cancer cells with
        deficiencies in DNA repair proteins other than BRCA1 and BRCA2.
  
        In melanoma, genetic HR mutation/ alterations are rather common. Retrospective data showed
        that nearly18-40% of melanoma harbors a mutation in at least 1 of the HR genes in their
        tumor. The commonly altered genes were ARID1A, FANCA, ATM, BRCA1, ATRX and BRCA2, ATR, BRCA1
        BRIP1 and SF3B1. These findings indicate that HR mutations / alterations are frequently
        observed in metastatic melanoma, and they suggest that PARP inhibitors could potentially be
        of a great clinical value in a substantial portion of the patients with advanced melanoma.
  
        In this clinical study, clinical efficacy of fluzoparib in combination with camrelizumab and
        temozolomide will be evaluated by assessing an objective clinical response rate in patients
        with advanced, metastatic melanoma with the homologous recombination (HR) pathway gene
        mutation / alteration.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective Response Rate (ORR)
  time frame: 6 months
  description: ORR of Fluzoparib in combination with Camrelizumab and Temozolomide in patients with advanced melanoma with genetic homologous recombination (HR) mutation/ alteration using RECIST v1.1
  arm group label: Camre+Fluzo+TMZ
  arm group type: Experimental
  description: This arm will enroll patients who has advanced melanoma with a genetic HR mutation/ alteration .
  intervention type: Drug
  intervention name: Fluzoparib Camrelizumab Temozolomide
  description: Fluzoparib 50-150mg bid po, d1-21, q3w Camrelizumab 200mg iv, d1, q3w Temozolomide 50mg/m2-200mg/m2 d1-5,q3w
  arm group label: Camre+Fluzo+TMZ
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Jun Guo
  role: Study Director
  affiliation: Peking University Cancer Hospital & Institute
  last name: Jun Guo
  phone: 86-10-88121122
  email: guoj307@126.com
  last name: Bin Lian
  phone: 86-10-88121122
  email: lianbin0214@126.com
  responsible party type: Sponsor-Investigator
  investigator affiliation: Peking University Cancer Hospital & Institute
  investigator full name: Jun Guo
  investigator title: Director
  mesh term: Melanoma
  mesh term: Temozolomide
  mesh term: Fluzoparib