<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/NCT03749187</url>
  </required_header>
  <id_info>
    <org_study_id>18083</org_study_id>
    <secondary_id>NCI-2018-02345</secondary_id>
    <secondary_id>PNOC017</secondary_id>
    <nct_id>NCT03749187</nct_id>
  </id_info>
  <brief_title>BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas</brief_title>
  <acronym>PNOC017</acronym>
  <official_title>A Target Validation/Phase1 Study of BGB-290 in Combination With Temozolomide in Adolescent and Young Adult IDH1/2 Newly Diagnosed and Recurrent Mutant Gliomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>BeiGene USA, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pacific Pediatric Neuro-Oncology Consortium</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</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>
      This phase I trial studies the side effects and best dose of BGB-290 and temozolomide in&#xD;
      treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma that is newly&#xD;
      diagnosed or has come back. BGB-290 may stop the growth of tumor cells by blocking some of&#xD;
      the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in&#xD;
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping&#xD;
      them from dividing, or by stopping them from spreading. Giving BGB-290 and temozolomide may&#xD;
      work better in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Determine the safety and tolerability of the combination of Poly (ADP-Ribose) polymerase&#xD;
      (PARP) inhibitor BGB-290 (BGB-290) and temozolomide (TMZ) in adolescent and young adult (AYA)&#xD;
      subjects with IDH1/2-mutant glioma, including the maximum tolerated dose (MTD) and&#xD;
      characterization of dose-limiting toxicities (DLTs) in both, newly diagnosed and recurrent&#xD;
      treatment arms.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. Evaluate the preliminary efficacy of BGB-290 and temozolomide in terms of progression free&#xD;
      survival (PFS) and overall survival (OS) in Arm A and B stratified by tumor diagnosis,&#xD;
      calculated using the Kaplan-Meier method with a goal of improving the historical high grade&#xD;
      glioma progression free survival of 10% and overall survival of 20% at 2 years.&#xD;
&#xD;
      II. Assess the mutational landscape studies via whole-exome sequencing (WES). III. Assessment&#xD;
      of gene expression patterns using ribonucleic acid (RNA) sequencing (RNAseq).&#xD;
&#xD;
      IV. Assess the methylation profiling with Infinium methylation assays. V. Assess the&#xD;
      oncometabolite profiling via liquid chromatography (LC)/mass spectrometry (MS)-MS.&#xD;
&#xD;
      VI. Assess the intratumoral drug level assessments via LC/MS-MS.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 cohorts. After the&#xD;
      MTD is established, additional patients will be enrolled into the efficacy component of the&#xD;
      trial.&#xD;
&#xD;
      Arm A: Newly diagnosed IDH1/2-mutant high-grade glioma patients receive PARP inhibitor&#xD;
      BGB-290 orally (PO) twice daily (BID) on days 1-28 and temozolomide PO daily on days 1-21.&#xD;
      Courses repeat every 28 days for up to 24 months in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      Arm B: Recurrent IDH1/2-mutant low-grade or high-grade glioma patients receive PARP inhibitor&#xD;
      BGB-290 orally (PO) twice daily (BID) on days 1-28 and temozolomide PO daily on days 1-21.&#xD;
      Courses repeat every 28 days for up to 24 months in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      COHORT B0: Recurrent IDH1/2-mutant low-grade or high-grade glioma patients receive PARP&#xD;
      inhibitor BGB-290 PO for 7 days pre-surgery at the MTD determined in the Phase I portion.&#xD;
      After recovery from surgery (14-28 days), the patient will proceed to the efficacy component&#xD;
      of the trial.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 3, 2019</start_date>
  <completion_date type="Anticipated">July 30, 2029</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of participants with Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Events occurring on or after treatment on Day 1 will be classified using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Adverse events leading to treatment discontinuation will be listed.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The analyses of PFS will include patients who have received any amount of study treatment. PFS is defined as the time from the first day of study treatment with until documented disease progression or death, whichever occurs first. For patients who do not have documented progressive disease (PD) or death before the end of the study or who are lost to follow-up, PFS will be censored at the day of the last clinical assessment. Data will be summarized by Kaplan-Meier method.</description>
  </other_outcome>
  <other_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The analyses of OS will include patients who have received any amount of study treatment. OS is defined as the time from the first dose of study treatment to the time of death from any cause on study. For patients who do not die before the end of the study or who are lost to follow-up, OS will be censored at the date of last contact. Data will be summarized by Kaplan-Meier method.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">78</enrollment>
  <condition>Glioblastoma</condition>
  <condition>IDH1 Gene Mutation</condition>
  <condition>IDH2 Gene Mutation</condition>
  <condition>Low Grade Glioma</condition>
  <condition>Malignant Glioma</condition>
  <condition>Recurrent Glioblastoma</condition>
  <condition>Recurrent WHO Grade II Glioma</condition>
  <condition>Recurrent WHO Grade III Glioma</condition>
  <condition>WHO Grade II Glioma</condition>
  <condition>WHO Grade III Glioma</condition>
  <arm_group>
    <arm_group_label>Arm A (BGB-290, temozolomide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with grades III-IV newly diagnosed IDH1/2 mutant glioma receive PARP inhibitor BGB-290 PO BID on days 1-28 and temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (BGB-290, temozolomide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with grades I-IV recurrent IDH1/2 mutant glioma receive PARP inhibitor BGB-290 PO BID on days 1-28 and temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.&#xD;
Cohort B0: Patients who are surgical candidates with grades I-IV recurrent IDH1/2 mutant glioma receive PARP inhibitor BGB-290 PO BID for 7 days, pre-surgery. After recovery from surgery, patients receive PARP inhibitor BGB-290 PO BID on days 1-28 and temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PARP Inhibitor BGB-290</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm A (BGB-290, temozolomide)</arm_group_label>
    <arm_group_label>Arm B (BGB-290, temozolomide)</arm_group_label>
    <other_name>BGB-290</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm A (BGB-290, temozolomide)</arm_group_label>
    <arm_group_label>Arm B (BGB-290, temozolomide)</arm_group_label>
    <other_name>CCRG-81045</other_name>
    <other_name>Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-</other_name>
    <other_name>M &amp; B 39831</other_name>
    <other_name>M and B 39831</other_name>
    <other_name>Methazolastone</other_name>
    <other_name>RP-46161</other_name>
    <other_name>SCH 52365</other_name>
    <other_name>Temcad</other_name>
    <other_name>Temodal</other_name>
    <other_name>Temodar</other_name>
    <other_name>Temomedac</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Arm A Only: Subjects must have histologically confirmed World Health Organization&#xD;
             (WHO) grade III-IV newly diagnosed IDH1/2-mutant glioma.&#xD;
&#xD;
          -  Arm B Only: WHO grades I-IV recurrent IDH1/2 mutant glioma. Subjects in Arm B must&#xD;
             have magnetic resonance imaging (MRI) confirming progressive disease; re-biopsy is&#xD;
             encouraged, but not required at the time of recurrence for confirmation.&#xD;
&#xD;
          -  Patients with a primary spinal tumor, secondary glioma, or multifocal disease in the&#xD;
             brain, but without evidence of diffuse leptomeningeal spread, are eligible. In cases&#xD;
             where there are questions about multifocality versus diffuse leptomeningeal spread,&#xD;
             the study chair or co-chair must be contacted to make a final decision on eligibility.&#xD;
&#xD;
          -  Subjects must have IDH1 or IDH2 mutation associated with neomorphic activity of the&#xD;
             encoded proteins.&#xD;
&#xD;
          -  Subjects must be willing to provide archival formalin-fixed embedded (FFPE) and frozen&#xD;
             tissue specimens for biomarker studies if available.&#xD;
&#xD;
          -  Subjects in Arm A must have been treated with maximal safe resection of primary tumor&#xD;
             followed by adjuvant radiation therapy (RT). Treatment with TMZ during radiation is&#xD;
             allowed but not required.&#xD;
&#xD;
          -  Subjects in Arm B must have been treated with maximal safe resection of tumor.&#xD;
&#xD;
               -  Lower grade glioma (LGG) subjects who progressed after initial surgery alone are&#xD;
                  eligible. Any number of prior therapies are allowed.&#xD;
&#xD;
               -  High grade glioma (HGG) subjects enrolled on Arm B must have been treated with a&#xD;
                  minimum of maximal safe resection of primary tumor followed by adjuvant RT prior&#xD;
                  to recurrence. Any number of prior therapies are allowed.&#xD;
&#xD;
          -  Subjects must have fully recovered from the acute toxic effects of all prior&#xD;
             chemotherapy, immunotherapy, or radiotherapy prior to entering this study.&#xD;
&#xD;
          -  Myelosuppressive chemotherapy: subjects must have received their last dose of known&#xD;
             myelosuppressive anticancer chemotherapy at least three weeks prior to study&#xD;
             registration or at least six weeks if nitrosourea.&#xD;
&#xD;
          -  Biologic agent: subjects must have recovered from any toxicity related to biologic&#xD;
             agents and received their last dose &gt;= 7 days prior to study registration.&#xD;
&#xD;
               -  For agents that have known adverse events occurring beyond 7 days after&#xD;
                  administration, this period must be extended beyond the time during which adverse&#xD;
                  events are known to occur. The duration of this interval should be discussed with&#xD;
                  the study chair.&#xD;
&#xD;
               -  For biologic agents that have a prolonged half-life, the appropriate interval&#xD;
                  since last treatment should be discussed with the study chair prior to&#xD;
                  registration.&#xD;
&#xD;
          -  Monoclonal antibody treatment: at least three half-lives must have elapsed prior to&#xD;
             registration, and subjects on bevacizumab must have received their last dose &gt;= 32&#xD;
             days prior to study registration.&#xD;
&#xD;
          -  Subjects in Arm A should begin therapy with TMZ and BGB-290 after completion of&#xD;
             radiation therapy and when all other eligibility criteria are met.&#xD;
&#xD;
          -  For subjects in Arm B, patients must not have received radiation therapy within 4&#xD;
             weeks prior to the initiation of study treatment. Post-RT, the diagnosis of true&#xD;
             progression versus ?pseudo-progression? can be challenging when imaging modalities are&#xD;
             exclusively used, and thus an additional resection is encouraged if clinically&#xD;
             indicated.&#xD;
&#xD;
          -  Peripheral absolute neutrophil count (ANC) &gt;= 1000/mm^3.&#xD;
&#xD;
          -  Platelet count &gt;= 100,000/mm^3 (transfusion independent, defined as not receiving&#xD;
             platelet transfusions for at least 7 days prior to enrollment).&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL.&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 x upper limit of normal (ULN) or estimated creatinine&#xD;
             clearance &gt;= 50 mL/min (calculated using the institutional standard method).&#xD;
&#xD;
          -  Total serum bilirubin (sum of conjugated + unconjugated) =&lt; 1.5 x upper limit of&#xD;
             normal (ULN).&#xD;
&#xD;
          -  Aspartate and alanine aminotransferase (AST and ALT) =&lt; 3 x ULN.&#xD;
&#xD;
          -  Serum albumin &gt;= 2 g/dL.&#xD;
&#xD;
          -  Subjects with seizure disorder may be enrolled if on non-enzyme inducing&#xD;
             anticonvulsants and well controlled.&#xD;
&#xD;
          -  Subjects who have neurological deficits should have deficits that are stable for a&#xD;
             minimum of 1 week prior to registration.&#xD;
&#xD;
          -  Corticosteroids: Subjects who are receiving dexamethasone must be on a stable or&#xD;
             decreasing dose for at least 1 week prior to registration.&#xD;
&#xD;
          -  The effects of BGB-290 on the developing human fetus are unknown. For this reason and&#xD;
             because alkylating agents (such as TMZ) are known to be teratogenic, women of&#xD;
             child-bearing potential and men must agree to use adequate contraception (hormonal or&#xD;
             barrier method of birth control; abstinence) prior to study entry, for the duration of&#xD;
             study participation and 4 months after completion of BGB-290 or TMZ administration.&#xD;
             Should a woman become pregnant or suspect she is pregnant while she or her partner is&#xD;
             participating in this study, she should inform her treating physician immediately.&#xD;
&#xD;
          -  Subjects must be able to swallow capsules.&#xD;
&#xD;
          -  Subjects must have the ability to undergo serial MRI scans (computerized tomography&#xD;
             [CT] cannot substitute for MRI).&#xD;
&#xD;
          -  A legal parent/guardian or patient must be able to understand, and willing to sign, a&#xD;
             written informed consent and assent document, as appropriate.&#xD;
&#xD;
          -  Karnofsky &gt;= 50 for subjects &gt; 16 years of age and Lansky &gt;= 50 for subjects =&lt; 16&#xD;
             years of age. Subjects who are unable to walk because of paralysis, but who are up in&#xD;
             a wheelchair, will be considered ambulatory for the purpose of assessing the&#xD;
             performance score.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who are receiving any other investigational agents and/or subjects previously&#xD;
             treated with small molecule inhibitors of mutant IDH1 or IDH2 proteins at any time may&#xD;
             not be enrolled.&#xD;
&#xD;
          -  Subjects who have received a PARP inhibitor previously.&#xD;
&#xD;
          -  Subjects with active infection requiring antibiotics at time of therapy start.&#xD;
&#xD;
          -  Subjects with other diagnosis of malignancy.&#xD;
&#xD;
          -  Subjects with clinically significant active bleeding disorder, hemoptysis, or melena&#xD;
             =&lt; 6 months prior to day 1.&#xD;
&#xD;
          -  Subjects on therapeutic anti-coagulation with heparin, warfarin, or other&#xD;
             anticoagulants:&#xD;
&#xD;
               -  Use of low-dose aspirin and/or non-steroidal anti-inflammatory agents are&#xD;
                  allowed.&#xD;
&#xD;
               -  Use of thrombolytic to establish patency of indwelling venous catheters is&#xD;
                  allowed.&#xD;
&#xD;
               -  Prophylactic anticoagulation for venous access devices is allowed as long as&#xD;
                  institutional normalized ratio (INR) is =&lt; 1.5 and partial thromboplastin time&#xD;
                  (aPTT) =&lt; 1.5 x institutional ULN.&#xD;
&#xD;
               -  Use of low-molecular weight heparin is allowed.&#xD;
&#xD;
          -  Subjects with known disseminated leptomeningeal disease.&#xD;
&#xD;
          -  Subjects with diffuse intrinsic pontine glioma (DIPG) are not eligible for this study.&#xD;
&#xD;
          -  Unresolved acute effects of any prior therapy of grade &gt;= 2, except for adverse events&#xD;
             (AEs) not constituting a safety risk by investigator judgement.&#xD;
&#xD;
          -  Use =&lt; 10 days (or =&lt; 5 half-lives, whichever is shorter) prior to day 1 or&#xD;
             anticipated need for food or drugs known to be strong or moderate Cytochrome P450,&#xD;
             family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to TMZ or BGB-290.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  Female subjects of childbearing potential must not be pregnant or breast-feeding.&#xD;
             Female subjects of childbearing potential must have a negative serum or urine&#xD;
             pregnancy test within 7 days of first dose.&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral&#xD;
             therapy are ineligible because of the potential for pharmacokinetic interactions with&#xD;
             BGB-290 and TMZ. In addition, these subjects are at increased risk of lethal&#xD;
             infections when treated with marrow-suppressive therapy.&#xD;
&#xD;
          -  Subjects with inability to return for follow-up visits or obtain follow-up studies&#xD;
             required to assess toxicity to therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sabine Mueller, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kelly Hitchner</last_name>
    <phone>415-502-1600</phone>
    <email>PNOC017@ucsf.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ashley S. Margol, MD</last_name>
      <phone>323-361-8147</phone>
      <email>amargol@chla.usc.edu</email>
    </contact>
    <investigator>
      <last_name>Ashley S. Margol, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tom Davidson, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rady Children's Hospital - San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jennifer Elster, MD</last_name>
      <phone>858-966-4939</phone>
      <email>jelster@rchsd.org</email>
    </contact>
    <investigator>
      <last_name>Jennifer Elster, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elise Witham</last_name>
      <phone>415-502-1600</phone>
      <email>PNOC_Regulatory@ucsf.edu</email>
    </contact>
    <contact_backup>
      <phone>877-827-3222</phone>
      <email>cancertrials@ucsf.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Sabine Mueller, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Asher M. Marks, MD</last_name>
      <phone>203-785-4640</phone>
      <email>asher.marks@yale.edu</email>
    </contact>
    <investigator>
      <last_name>Asher M. Marks, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lindsay B. Kilburn, MD</last_name>
      <phone>202-476-5973</phone>
      <email>lkilburn@cnmc.org</email>
    </contact>
    <investigator>
      <last_name>Lindsay B. Kilburn, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Florida Health Science Center - Gainesville</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sridharan Gururangan</last_name>
      <phone>352-294-8347</phone>
      <email>Sridharan.Gururangan@neurosurgery.ufl.edu</email>
    </contact>
    <investigator>
      <last_name>Sridharan Gururangan</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University/Sidney Kimmel Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kenneth J. Cohen, MD, MBA</last_name>
      <phone>410-614-5055</phone>
      <email>kcohen@jhmi.edu</email>
    </contact>
    <investigator>
      <last_name>Kenneth J. Cohen, MD, MBA</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tabitha Cooney, MD</last_name>
      <phone>617-632-2291</phone>
      <email>tabitha_cooney@dfci.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Tabitha Cooney, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mohamed Abdelbaki, MD</last_name>
      <phone>314-286-2790</phone>
      <email>MohamedA@wustl.edu</email>
    </contact>
    <investigator>
      <last_name>Mohamed Abdelbaki, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Margot Lazow, MD</last_name>
      <phone>614-722-4087</phone>
      <email>margot.lazow@nationwidechildrens.org</email>
    </contact>
    <investigator>
      <last_name>Margot Lazow, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Linda Stork, MD</last_name>
      <phone>614-722-4087</phone>
      <email>storkl@ohsu.edu</email>
    </contact>
    <investigator>
      <last_name>Linda Stork, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cassie Kline, MD</last_name>
      <email>KlineC@EMAIL.CHOP.EDU</email>
    </contact>
    <investigator>
      <last_name>Cassie Kline, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amar Gajjar, MD</last_name>
      <phone>901-595-2615</phone>
      <email>amar.gajjar@stjude.org</email>
    </contact>
    <investigator>
      <last_name>Amar Gajjar, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute/University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Nicholas S. Whipple, MD, MPH</last_name>
      <phone>801-662-4700</phone>
      <email>whipple@hsc.utah.edu</email>
    </contact>
    <investigator>
      <last_name>Nicholas S. Whipple, MD, MPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
  </removed_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>April 4, 2023</last_update_submitted>
  <last_update_submitted_qc>April 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Sabine Mueller, MD, PhD</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
    <mesh_term>Glioma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</mesh_term>
    <mesh_term>Pamiparib</mesh_term>
    <mesh_term>Poly(ADP-ribose) Polymerase Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03749187
org study id: 18083
secondary id: NCI-2018-02345
secondary id: PNOC017
nct id: NCT03749187
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This phase I trial studies the side effects and best dose of BGB-290 and temozolomide in
      treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma that is newly
      diagnosed or has come back. BGB-290 may stop the growth of tumor cells by blocking some of
      the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Giving BGB-290 and temozolomide may
      work better in treating adolescents and young adults with IDH1/2-mutant grade I-IV glioma.
PRIMARY OBJECTIVES:

      I. Determine the safety and tolerability of the combination of Poly (ADP-Ribose) polymerase
      (PARP) inhibitor BGB-290 (BGB-290) and temozolomide (TMZ) in adolescent and young adult (AYA)
      subjects with IDH1/2-mutant glioma, including the maximum tolerated dose (MTD) and
      characterization of dose-limiting toxicities (DLTs) in both, newly diagnosed and recurrent
      treatment arms.

      EXPLORATORY OBJECTIVES:

      I. Evaluate the preliminary efficacy of BGB-290 and temozolomide in terms of progression free
      survival (PFS) and overall survival (OS) in Arm A and B stratified by tumor diagnosis,
      calculated using the Kaplan-Meier method with a goal of improving the historical high grade
      glioma progression free survival of 10% and overall survival of 20% at 2 years.

      II. Assess the mutational landscape studies via whole-exome sequencing (WES). III. Assessment
      of gene expression patterns using ribonucleic acid (RNA) sequencing (RNAseq).

      IV. Assess the methylation profiling with Infinium methylation assays. V. Assess the
      oncometabolite profiling via liquid chromatography (LC)/mass spectrometry (MS)-MS.

      VI. Assess the intratumoral drug level assessments via LC/MS-MS.

      OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 cohorts. After the
      MTD is established, additional patients will be enrolled into the efficacy component of the
      trial.

      Arm A: Newly diagnosed IDH1/2-mutant high-grade glioma patients receive PARP inhibitor
      BGB-290 orally (PO) twice daily (BID) on days 1-28 and temozolomide PO daily on days 1-21.
      Courses repeat every 28 days for up to 24 months in the absence of disease progression or
      unacceptable toxicity.

      Arm B: Recurrent IDH1/2-mutant low-grade or high-grade glioma patients receive PARP inhibitor
      BGB-290 orally (PO) twice daily (BID) on days 1-28 and temozolomide PO daily on days 1-21.
      Courses repeat every 28 days for up to 24 months in the absence of disease progression or
      unacceptable toxicity.

      COHORT B0: Recurrent IDH1/2-mutant low-grade or high-grade glioma patients receive PARP
      inhibitor BGB-290 PO for 7 days pre-surgery at the MTD determined in the Phase I portion.
      After recovery from surgery (14-28 days), the patient will proceed to the efficacy component
      of the trial.

      After completion of study treatment, patients are followed up for 5 years.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of participants with Dose Limiting Toxicities (DLTs)
time frame: Up to 28 days
description: Events occurring on or after treatment on Day 1 will be classified using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Adverse events leading to treatment discontinuation will be listed.
measure: Progression free survival (PFS)
time frame: Up to 5 years
description: The analyses of PFS will include patients who have received any amount of study treatment. PFS is defined as the time from the first day of study treatment with until documented disease progression or death, whichever occurs first. For patients who do not have documented progressive disease (PD) or death before the end of the study or who are lost to follow-up, PFS will be censored at the day of the last clinical assessment. Data will be summarized by Kaplan-Meier method.
measure: Overall survival (OS)
time frame: Up to 5 years
description: The analyses of OS will include patients who have received any amount of study treatment. OS is defined as the time from the first dose of study treatment to the time of death from any cause on study. For patients who do not die before the end of the study or who are lost to follow-up, OS will be censored at the date of last contact. Data will be summarized by Kaplan-Meier method.
arm group label: Arm A (BGB-290, temozolomide)
arm group type: Experimental
description: Patients with grades III-IV newly diagnosed IDH1/2 mutant glioma receive PARP inhibitor BGB-290 PO BID on days 1-28 and temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
arm group label: Arm B (BGB-290, temozolomide)
arm group type: Experimental
description: Patients with grades I-IV recurrent IDH1/2 mutant glioma receive PARP inhibitor BGB-290 PO BID on days 1-28 and temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Cohort B0: Patients who are surgical candidates with grades I-IV recurrent IDH1/2 mutant glioma receive PARP inhibitor BGB-290 PO BID for 7 days, pre-surgery. After recovery from surgery, patients receive PARP inhibitor BGB-290 PO BID on days 1-28 and temozolomide PO daily on days 1-21. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: PARP Inhibitor BGB-290
description: Given PO
arm group label: Arm A (BGB-290, temozolomide)
arm group label: Arm B (BGB-290, temozolomide)
other name: BGB-290
intervention type: Drug
intervention name: Temozolomide
description: Given PO
arm group label: Arm A (BGB-290, temozolomide)
arm group label: Arm B (BGB-290, temozolomide)
other name: CCRG-81045
other name: Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
other name: M & B 39831
other name: M and B 39831
other name: Methazolastone
other name: RP-46161
other name: SCH 52365
other name: Temcad
other name: Temodal
other name: Temodar
other name: Temomedac
criteria: 
gender: All
minimum age: 13 Years
maximum age: 25 Years
healthy volunteers: No
last name: Sabine Mueller, MD, PhD
role: Principal Investigator
affiliation: University of California, San Francisco
last name: Kelly Hitchner
phone: 415-502-1600
email: PNOC017@ucsf.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
country: United States
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Sabine Mueller, MD, PhD
investigator title: Associate Professor
mesh term: Glioblastoma
mesh term: Glioma
mesh term: Recurrence
mesh term: Temozolomide
mesh term: Pamiparib
mesh term: Poly(ADP-ribose) Polymerase Inhibitors
sharing ipd: No