<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/NCT03840967</url>
  </required_header>
  <id_info>
    <org_study_id>HCRN ESO17-325</org_study_id>
    <nct_id>NCT03840967</nct_id>
  </id_info>
  <brief_title>A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma</brief_title>
  <official_title>A Phase II Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Homologous Recombination (HR) Defective or Loss of Heterozygosity (LOH) High Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shadia Jalal, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Indiana University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hoosier Cancer Research Network</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      Patients can be prescreened for the study at the time of diagnosis of locally advanced or&#xD;
      metastatic disease by determining presence of LOH high status and/or deleterious alterations&#xD;
      in HR pathway genes in the most recent available tumor tissue sample or in blood if they are&#xD;
      found to have germline mutations. Patients with either somatic or germline mutations will be&#xD;
      allowed. At the time of disease progression, patients with high LOH or deleterious&#xD;
      alterations in HR pathway genes and satisfying all other inclusion criteria will be enrolled&#xD;
      on the study. Patients will be treated with niraparib (flat dose) orally every day for 28&#xD;
      days until disease progression, unacceptable side effects, withdrawal of consent, or death.&#xD;
      CT of the chest/abdomen/pelvis will be performed every 2 months and response will be assessed&#xD;
      by RECIST 1.1.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 9, 2019</start_date>
  <completion_date type="Anticipated">November 2024</completion_date>
  <primary_completion_date type="Anticipated">November 2023</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>Objective Response Rate</measure>
    <time_frame>2 years</time_frame>
    <description>Determine objective response rate (ORR) with niraparib in patients with metastatic esophageal/gastroesophageal junction (GEJ)/proximal gastric adenocarcinoma previously treated with platinum containing chemotherapy and harboring high genome wide loss of heterozygosity (LOH) or defective homologous recombination noted through deleterious alterations in HR genes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess adverse events</measure>
    <time_frame>2 years</time_frame>
    <description>Evaluate the safety and tolerability of niraparib as defined by CTCAE v5.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>3 years</time_frame>
    <description>PFS is defined as the time from D1 of treatment until the criteria for disease progression is met as defined by RECIST 1.1 or death as a result of any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate</measure>
    <time_frame>2 years</time_frame>
    <description>Disease control rate is defined as the proportion of all subjects with stable disease (SD) for 8 weeks, or partial response (PR), or complete response (CR) according to RECIST 1.1.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">43</enrollment>
  <condition>Esophageal Cancer</condition>
  <condition>Gastric Cancer</condition>
  <condition>Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Niraparib</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Niraparib</intervention_name>
    <description>Niraparib will be administered as a flat-fixed daily dose depending on weight and platelet count. Subjects will take orally on a daily basis for 28 days. Each cycle = 28 days</description>
    <arm_group_label>Niraparib</arm_group_label>
    <other_name>Zejula</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent and HIPAA authorization for release of personal health&#xD;
             information. NOTE: HIPAA authorization may be included in the informed consent or&#xD;
             obtained separately.&#xD;
&#xD;
          2. Age ≥ 18 years at the time of consent.&#xD;
&#xD;
          3. ECOG Performance Status of 0-1 within 14 days prior to registration.&#xD;
&#xD;
          4. Locally advanced esophageal adenocarcinoma or proximal gastric adenocarcinoma or&#xD;
             metastatic adenocarcinoma originating from esophagus, GE junction, or proximal stomach&#xD;
             who progress/recur beyond 2 months of receiving a platinum- containing regimen&#xD;
&#xD;
             NOTE: Patients can be pre-screened for study at any time including after surgical&#xD;
             resection for locally advanced esophageal cancer, at presentation with metastatic&#xD;
             disease and potentially during chemotherapy and radiation prior to surgery.&#xD;
&#xD;
          5. A subject with symptomatic brain metastasis may be considered if they have completed&#xD;
             their treatment for brain metastasis at least 4 weeks prior to study registration,&#xD;
             have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic. Patients with&#xD;
             asymptomatic brain mets that are untreated will be allowed.&#xD;
&#xD;
          6. Must not have received more than 1 prior line of chemotherapy in the metastatic&#xD;
             setting (could have received immunotherapy, VEGF directed therapy, and/or trastuzumab&#xD;
             which does not count as chemotherapy).&#xD;
&#xD;
          7. One of the following genetic results is required for eligibility:&#xD;
&#xD;
               -  High LOH in tissue OR&#xD;
&#xD;
               -  HR mutation in tissue OR&#xD;
&#xD;
               -  Germline mutation (blood)&#xD;
&#xD;
             NOTE: Mutations, deletions or loss by fusions are the acceptable alterations in HR&#xD;
             genes as long as they are deleterious. Patients are eligible if they have a mutation&#xD;
             in pre-specified HR genes BRCA1/2, PALB2, ATM, BARD1, BRIP1, CDK12, CHEK2, FANCA,&#xD;
             RAD51, RAD51B, RAD51C, RAD51D, RAD54L, NBN, ARID1A and GEN1. Deleterious mutations in&#xD;
             HR genes are defined as those that have been previously characterized to be&#xD;
             loss-of-function/pathogenic/or likely pathogenic as specified per the following&#xD;
             databases: Clinvar, OncoKB, or BRCAExchange. Mutations or small insertions or&#xD;
             deletions that results in truncation, frameshift, stop codon loss, or stop codon gain&#xD;
             will also be considered deleterious irrespective of their presence in the&#xD;
             aforementioned databases unless previously characterized to be benign. Copy number&#xD;
             losses or disruption by fusion will also be considered deleterious irrespective of&#xD;
             their presence in the aforementioned databases. Gene amplifications or variants of&#xD;
             unknown significance will not be eligible for inclusion.&#xD;
&#xD;
             NOTE: Genetic testing results from a CLIA certified lab that confirm one of the&#xD;
             following: high LOH in tissue, HR mutation in tissue or germline mutation in blood are&#xD;
             required and can be used to meet eligibility. Even if subject has met eligibility with&#xD;
             one of the criteria above, results from the other analysis is required if available.&#xD;
&#xD;
             If prior genetic results are not available, subject must have archival tissue or fresh&#xD;
             tissue (by new biopsy) for testing. Both primary tumor tissue and metastatic site&#xD;
             sample biopsies are allowed. Blood will also be required for germline mutation&#xD;
             analyses. Central confirmation of all results will be performed but are not mandated&#xD;
             for eligibility. If a subject has met eligibility with prior genetic results but does&#xD;
             not have sufficient archival tissue for central confirmation, a biopsy is not&#xD;
             required.&#xD;
&#xD;
          8. Presence of measurable disease by RECIST v1.1, defined as:&#xD;
&#xD;
               -  Tumor lesions that must be accurately measured in at least one dimension (longest&#xD;
                  diameter in the plane of measurement is to be recorded) with a minimum size of:&#xD;
&#xD;
                    -  10 mm by CT scan (CT scan slice thickness no greater than 5 mm)&#xD;
&#xD;
                    -  10 mm caliper measurement by clinical exam (lesions which cannot be&#xD;
                       accurately measured with calipers should be recorded as non-measurable)&#xD;
&#xD;
                    -  20 mm by chest X-ray&#xD;
&#xD;
               -  Malignant lymph nodes: To be considered pathologically enlarged and measurable, a&#xD;
                  lymph node must be ≥ 15 mm in short axis when assessed by CT scan (CT scan slice&#xD;
                  thickness recommended to be no greater than 5 mm). At baseline and in follow-up,&#xD;
                  only the short axis will be measured and followed.&#xD;
&#xD;
          9. Prior cancer treatment must be completed at least 14 days prior to registration and&#xD;
             the subject must have recovered from all reversible acute toxic effects of the regimen&#xD;
             (other than alopecia) to ≤ Grade 1 or baseline.&#xD;
&#xD;
         10. Demonstrate adequate organ function as defined in the table below; all screening labs&#xD;
             to be obtained within 14 days prior to registration.&#xD;
&#xD;
               -  Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3&#xD;
&#xD;
               -  Hemoglobin (Hgb) ≥ 9 g/dL&#xD;
&#xD;
               -  Platelet Count (Plt) ≥ 100 K/ mm3&#xD;
&#xD;
               -  Creatinine ≤ 1.5 X upper limit of normal (ULN)&#xD;
&#xD;
               -  Bilirubin ≤ 1.5× ULN ((≤2.0 in patients with known Gilberts syndrome))&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) ≤ 2.5× ULN*&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) ≤ 2.5 × ULN*&#xD;
&#xD;
         11. Females of childbearing potential must have a negative pregnancy test within 7 days&#xD;
             prior to study treatment. Urine or serum βhCG if clinically appropriate. If a urine&#xD;
             test is done and it is positive or cannot be confirmed as negative, a serum pregnancy&#xD;
             test will be required. NOTE: Females are considered of child bearing potential unless&#xD;
             they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation,&#xD;
             or bilateral oophorectomy) or they are naturally postmenopausal for at least 12&#xD;
             consecutive months.&#xD;
&#xD;
         12. Females of childbearing potential must be willing to abstain from heterosexual&#xD;
             intercourse or use adequate contraception as described in the protocol. Males must be&#xD;
             willing to abstain from heterosexual intercourse or use adequate contraception as&#xD;
             described in the protocol.&#xD;
&#xD;
         13. Participants must agree to not breastfeed during the study or for 30 days after the&#xD;
             last dose of study treatment.&#xD;
&#xD;
         14. As determined by the enrolling physician or protocol designee, ability of the subject&#xD;
             to understand and comply with study procedures for the entire length of the study.&#xD;
&#xD;
         15. Participant must agree to not donate blood during the study or for 90 days after the&#xD;
             last dose of study treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior therapy with a PARP inhibitor&#xD;
&#xD;
          2. Disease progression during first 2 months of standard dose platinum-based chemotherapy&#xD;
             (platinum refractory). This excludes low dose platinum based therapy that is given in&#xD;
             a chemotherapy-radiation regimen for locally advanced esophageal cancer.&#xD;
&#xD;
          3. Participant must not be simultaneously enrolled in any other interventional clinical&#xD;
             trial.&#xD;
&#xD;
          4. Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol&#xD;
             therapy and participant must have recovered from any surgical effects.&#xD;
&#xD;
          5. Participant must not have received investigational therapy ≤ 4 weeks, or within a time&#xD;
             interval less than at least 5 half-lives of the investigational agent, whichever is&#xD;
             shorter, prior initiating protocol therapy.&#xD;
&#xD;
          6. Participant has had radiation therapy encompassing &gt;20% of the bone marrow within 2&#xD;
             weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.&#xD;
&#xD;
          7. Participant must not have a known hypersensitivity to niraparib components or&#xD;
             excipients including tartrazine.&#xD;
&#xD;
          8. Participant must not have received a transfusion (platelets or red blood cells) ≤ 4&#xD;
             weeks prior to initiating protocol therapy.&#xD;
&#xD;
          9. Participant must not have received colony stimulating factors (e.g., granulocyte&#xD;
             colony-stimulating factor, granulocyte macrophage colony stimulating factor, or&#xD;
             recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.&#xD;
&#xD;
         10. Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due&#xD;
             to prior chemotherapy that persisted &gt; 4 weeks and was related to the most recent&#xD;
             treatment.&#xD;
&#xD;
         11. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute&#xD;
             myeloid leukemia (AML).&#xD;
&#xD;
         12. Participant must not have a serious, uncontrolled medical disorder, nonmalignant&#xD;
             systemic disease, or active, uncontrolled infection. Examples include, but are not&#xD;
             limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial&#xD;
             infarction, uncontrolled major seizure disorder, unstable spinal cord compression,&#xD;
             superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining&#xD;
             informed consent.&#xD;
&#xD;
         13. No active secondary cancer&#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>Shadia Jalal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University Melvin and Bren Simon Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana Univeristy Melvin and Bren Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Health System</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>February 12, 2019</study_first_submitted>
  <study_first_submitted_qc>February 13, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>May 10, 2023</last_update_submitted>
  <last_update_submitted_qc>May 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Hoosier Cancer Research Network</investigator_affiliation>
    <investigator_full_name>Shadia Jalal, MD</investigator_full_name>
    <investigator_title>Sponsor-Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Niraparib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03840967
org study id: HCRN ESO17-325
nct id: NCT03840967
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Patients can be prescreened for the study at the time of diagnosis of locally advanced or
      metastatic disease by determining presence of LOH high status and/or deleterious alterations
      in HR pathway genes in the most recent available tumor tissue sample or in blood if they are
      found to have germline mutations. Patients with either somatic or germline mutations will be
      allowed. At the time of disease progression, patients with high LOH or deleterious
      alterations in HR pathway genes and satisfying all other inclusion criteria will be enrolled
      on the study. Patients will be treated with niraparib (flat dose) orally every day for 28
      days until disease progression, unacceptable side effects, withdrawal of consent, or death.
      CT of the chest/abdomen/pelvis will be performed every 2 months and response will be assessed
      by RECIST 1.1.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate
time frame: 2 years
description: Determine objective response rate (ORR) with niraparib in patients with metastatic esophageal/gastroesophageal junction (GEJ)/proximal gastric adenocarcinoma previously treated with platinum containing chemotherapy and harboring high genome wide loss of heterozygosity (LOH) or defective homologous recombination noted through deleterious alterations in HR genes.
measure: Assess adverse events
time frame: 2 years
description: Evaluate the safety and tolerability of niraparib as defined by CTCAE v5.
measure: Progression free survival
time frame: 3 years
description: PFS is defined as the time from D1 of treatment until the criteria for disease progression is met as defined by RECIST 1.1 or death as a result of any cause, whichever occurs first.
measure: Disease Control Rate
time frame: 2 years
description: Disease control rate is defined as the proportion of all subjects with stable disease (SD) for 8 weeks, or partial response (PR), or complete response (CR) according to RECIST 1.1.
arm group label: Niraparib
arm group type: Other
intervention type: Drug
intervention name: Niraparib
description: Niraparib will be administered as a flat-fixed daily dose depending on weight and platelet count. Subjects will take orally on a daily basis for 28 days. Each cycle = 28 days
arm group label: Niraparib
other name: Zejula
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shadia Jalal, MD
role: Principal Investigator
affiliation: Indiana University Melvin and Bren Simon Cancer Center
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Hoosier Cancer Research Network
investigator full name: Shadia Jalal, MD
investigator title: Sponsor-Investigator
mesh term: Adenocarcinoma
mesh term: Niraparib
sharing ipd: Undecided