<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/NCT03233204</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2017-00766</org_study_id>
    <secondary_id>NCI-2017-00766</secondary_id>
    <secondary_id>APEC1621H</secondary_id>
    <secondary_id>APEC1621H</secondary_id>
    <secondary_id>APEC1621H</secondary_id>
    <secondary_id>U10CA180886</secondary_id>
    <nct_id>NCT03233204</nct_id>
  </id_info>
  <brief_title>Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)</brief_title>
  <official_title>NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)- A Phase 2 Subprotocol of Olaparib in Patients With Tumors Harboring Defects in DNA Damage Repair Genes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II Pediatric MATCH trial studies how well olaparib works in treating patients with&#xD;
      solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with defects in deoxyribonucleic&#xD;
      acid (DNA) damage repair genes that have spread to other places in the body (advanced) and&#xD;
      have come back (relapsed) or do not respond to treatment (refractory). Olaparib is an&#xD;
      inhibitor of PARP, an enzyme that helps repair DNA when it becomes damaged. Blocking PARP may&#xD;
      help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors&#xD;
      are a type of targeted therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine the objective response rate (ORR; complete response + partial response) in&#xD;
      pediatric patients treated with olaparib with advanced solid tumors (including central&#xD;
      nervous system [CNS] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor&#xD;
      activating genetic alterations in the deleterious genetic alterations in the DNA damage&#xD;
      repair (DDR) pathway.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate the progression free survival in pediatric patients treated with olaparib with&#xD;
      advanced solid tumors including non-Hodgkin lymphomas, CNS tumors, and histiocytosis that&#xD;
      harbor deleterious genetic alterations in the DDR pathway.&#xD;
&#xD;
      II. To obtain information about the tolerability of olaparib in children and adolescents with&#xD;
      relapsed or refractory cancer.&#xD;
&#xD;
      III. To provide preliminary estimates of the pharmacokinetics of olaparib in children and&#xD;
      adolescents with relapsed or refractory cancer.&#xD;
&#xD;
      EXPLORATORY OBJECTIVE:&#xD;
&#xD;
      I. To explore approaches to profiling changes in tumor genomics over time through the&#xD;
      evaluation of circulating tumor DNA.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28&#xD;
      days for 2 years in the absence of disease progression or unacceptable toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 24, 2017</start_date>
  <completion_date type="Anticipated">May 9, 2024</completion_date>
  <primary_completion_date type="Actual">March 31, 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 (complete response/partial response)</measure>
    <time_frame>From enrollment to the end of treatment, up to 2 years</time_frame>
    <description>Determined using Response Evaluation Criteria in Solid Tumors version 1.1. A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>From the initiation of protocol treatment to the occurrence of disease progression, disease recurrence, or death from any cause, assessed up to 4 years</time_frame>
    <description>PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Experiencing Grade 3 or Higher Adverse Events</measure>
    <time_frame>From enrollment to 30 days after the end of treatment, up to 2 years</time_frame>
    <description>Percentage of patients experiencing grade 3 or higher adverse events will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All patients who receive at least one dose of protocol therapy will be considered in the evaluation of toxicity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of olaparib</measure>
    <time_frame>Pre-dose on day 1, and pre-dose, 1, 2, 4, and 6-8 hours after morning dose on day 8 of cycle 1</time_frame>
    <description>A descriptive analysis of PK parameters will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in tumor genomic profile</measure>
    <time_frame>Cycle 5 day 1 to 4 years</time_frame>
    <description>Approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid will be explored. Descriptive analysis will be performed and will be summarized with simple summary statistics.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Advanced Malignant Solid Neoplasm</condition>
  <condition>Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma</condition>
  <condition>Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma</condition>
  <condition>Low Grade Glioma</condition>
  <condition>Malignant Glioma</condition>
  <condition>Recurrent Childhood Central Nervous System Neoplasm</condition>
  <condition>Recurrent Childhood Ependymoma</condition>
  <condition>Recurrent Childhood Malignant Germ Cell Tumor</condition>
  <condition>Recurrent Childhood Non-Hodgkin Lymphoma</condition>
  <condition>Recurrent Childhood Rhabdomyosarcoma</condition>
  <condition>Recurrent Childhood Soft Tissue Sarcoma</condition>
  <condition>Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor</condition>
  <condition>Recurrent Glioma</condition>
  <condition>Recurrent Hepatoblastoma</condition>
  <condition>Recurrent Langerhans Cell Histiocytosis</condition>
  <condition>Recurrent Malignant Solid Neoplasm</condition>
  <condition>Recurrent Medulloblastoma</condition>
  <condition>Recurrent Neuroblastoma</condition>
  <condition>Recurrent Osteosarcoma</condition>
  <condition>Refractory Childhood Malignant Germ Cell Tumor</condition>
  <condition>Refractory Ependymoma</condition>
  <condition>Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor</condition>
  <condition>Refractory Glioma</condition>
  <condition>Refractory Hepatoblastoma</condition>
  <condition>Refractory Langerhans Cell Histiocytosis</condition>
  <condition>Refractory Malignant Glioma</condition>
  <condition>Refractory Malignant Solid Neoplasm</condition>
  <condition>Refractory Medulloblastoma</condition>
  <condition>Refractory Neuroblastoma</condition>
  <condition>Refractory Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Osteosarcoma</condition>
  <condition>Refractory Primary Central Nervous System Neoplasm</condition>
  <condition>Refractory Rhabdomyosarcoma</condition>
  <condition>Refractory Soft Tissue Sarcoma</condition>
  <condition>Rhabdoid Tumor</condition>
  <condition>Wilms Tumor</condition>
  <arm_group>
    <arm_group_label>Treatment (olaparib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olaparib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (olaparib)</arm_group_label>
    <other_name>AZD 2281</other_name>
    <other_name>AZD-2281</other_name>
    <other_name>AZD2281</other_name>
    <other_name>KU-0059436</other_name>
    <other_name>Lynparza</other_name>
    <other_name>Olanib</other_name>
    <other_name>Olaparix</other_name>
    <other_name>PARP Inhibitor AZD2281</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient must have enrolled onto APEC1621SC (NCT03155620) and must have been given a&#xD;
             treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621H&#xD;
             based on the presence of an actionable mutation&#xD;
&#xD;
          -  Patients must be &gt;= than 12 months and =&lt; 21 years of age at the time of study&#xD;
             enrollment&#xD;
&#xD;
          -  Patients must have a body surface area &gt;= 0.65 m^2 at enrollment&#xD;
&#xD;
          -  Patients must have radiographically measurable disease at the time of study&#xD;
             enrollment; patients with neuroblastoma who do not have measurable disease but have&#xD;
             iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in&#xD;
             patients with CNS involvement is defined as tumor that is measurable in two&#xD;
             perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than&#xD;
             one slice&#xD;
&#xD;
               -  Note: The following do not qualify as measurable disease:&#xD;
&#xD;
                    -  Malignant fluid collections (e.g., ascites, pleural effusions)&#xD;
&#xD;
                    -  Bone marrow infiltration except that detected by MIBG scan for neuroblastoma&#xD;
&#xD;
                    -  Lesions only detected by nuclear medicine studies (e.g., bone, gallium or&#xD;
                       positron emission tomography [PET] scans) except as noted for neuroblastoma&#xD;
&#xD;
                    -  Elevated tumor markers in plasma or cerebrospinal fluid (CSF)&#xD;
&#xD;
                    -  Previously radiated lesions that have not demonstrated clear progression&#xD;
                       post radiation&#xD;
&#xD;
                    -  Leptomeningeal lesions that do not meet the measurement requirements for&#xD;
                       Response Evaluation Criteria in Solid Tumors (RECIST) 1.1&#xD;
&#xD;
          -  Karnofsky &gt;= 50% for patients &gt; 16 years of age and Lansky &gt;= 50 for patients =&lt; 16&#xD;
             years of age&#xD;
&#xD;
               -  Note: Neurologic deficits in patients with CNS tumors must have been relatively&#xD;
                  stable for at least 7 days prior to study enrollment; patients who are unable to&#xD;
                  walk because of paralysis, but who are up in a wheelchair, will be considered&#xD;
                  ambulatory for the purpose of assessing the performance score&#xD;
&#xD;
          -  Patients must have fully recovered from the acute toxic effects of all prior&#xD;
             anti-cancer therapy and must meet the following minimum duration from prior&#xD;
             anti-cancer directed therapy prior to enrollment; if after the required timeframe, the&#xD;
             numerical eligibility criteria are met, e.g. blood count criteria, the patient is&#xD;
             considered to have recovered adequately&#xD;
&#xD;
               -  Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive&#xD;
&#xD;
                    -  &gt;= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy&#xD;
                       (42 days if prior nitrosourea)&#xD;
&#xD;
               -  Anti-cancer agents not known to be myelosuppressive (e.g. not associated with&#xD;
                  reduced platelet or absolute neutrophil count [ANC] counts): &gt;= 7 days after the&#xD;
                  last dose of agent&#xD;
&#xD;
               -  Antibodies: &gt;= 21 days must have elapsed from infusion of last dose of antibody,&#xD;
                  and toxicity related to prior antibody therapy must be recovered to grade =&lt; 1&#xD;
&#xD;
               -  Corticosteroids: If used to modify immune adverse events related to prior&#xD;
                  therapy, &gt;= 14 days must have elapsed since last dose of corticosteroid&#xD;
&#xD;
               -  Hematopoietic growth factors: &gt;= 14 days after the last dose of a long-acting&#xD;
                  growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for&#xD;
                  growth factors 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 must be discussed with&#xD;
                  the study chair and the study-assigned research coordinator&#xD;
&#xD;
               -  Interleukins, interferons and cytokines (other than hematopoietic growth&#xD;
                  factors): &gt;= 21 days after the completion of interleukins, interferon or&#xD;
                  cytokines (other than hematopoietic growth factors)&#xD;
&#xD;
               -  Stem cell infusions (with or without total body irradiation [TBI]):&#xD;
&#xD;
                    -  Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem&#xD;
                       cell infusion including donor lymphocyte infusion (DLI) or boost infusion:&#xD;
                       &gt;= 84 days after infusion and no evidence of graft versus host disease&#xD;
                       (GVHD)&#xD;
&#xD;
                    -  Autologous stem cell infusion including boost infusion: &gt;= 42 days&#xD;
&#xD;
               -  Cellular therapy: &gt;= 42 days after the completion of any type of cellular therapy&#xD;
                  (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)&#xD;
&#xD;
               -  Radiation therapy (XRT)/external beam irradiation including protons: &gt;= 14 days&#xD;
                  after local XRT; &gt;= 150 days after TBI, craniospinal XRT or if radiation to &gt;=&#xD;
                  50% of the pelvis; &gt;= 42 days if other substantial bone marrow (BM) radiation&#xD;
&#xD;
                    -  Note: Radiation may not be delivered to &quot;measurable disease&quot; tumor site(s)&#xD;
                       being used to follow response to subprotocol treatment&#xD;
&#xD;
               -  Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131iodine [I]-MIBG): &gt;=&#xD;
                  42 days after systemically administered radiopharmaceutical therapy&#xD;
&#xD;
               -  Patients must not have received prior exposure to olaparib, veliparib, niraparib,&#xD;
                  rucaparib, talazoparib or other poly adenosine diphosphate ribose polymerase&#xD;
                  inhibitors (PARPi)&#xD;
&#xD;
          -  For patients with solid tumors without known bone marrow involvement: peripheral&#xD;
             absolute neutrophil count (ANC) &gt;= 1000/mm^3 (within 7 days prior to enrollment)&#xD;
&#xD;
          -  For patients with solid tumors without known bone marrow involvement: platelet count&#xD;
             &gt;= 100,000/mm^3 (within 7 days prior to enrollment) (transfusion independent, defined&#xD;
             as not receiving platelet transfusions for at least 7 days prior to enrollment)&#xD;
&#xD;
          -  Patients with known bone marrow metastatic disease will be eligible for study provided&#xD;
             they meet the blood counts (may receive platelet or packed red blood cells [pRBC]&#xD;
             transfusions provided they are not known to be refractory to red cell or platelet&#xD;
             transfusions); these patients will not be evaluable for hematologic toxicity&#xD;
&#xD;
          -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) &gt;= 70&#xD;
             ml/min/1.73 m^2 (within 7 days prior to enrollment) or&#xD;
&#xD;
          -  A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):&#xD;
&#xD;
               -  Age 1 to &lt; 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for&#xD;
                  female&#xD;
&#xD;
               -  Age 2 to &lt; 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for&#xD;
                  female&#xD;
&#xD;
               -  Age 6 to &lt; 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for&#xD;
                  female&#xD;
&#xD;
               -  Age 10 to &lt; 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL&#xD;
                  for female&#xD;
&#xD;
               -  Age 13 to &lt; 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL&#xD;
                  for female&#xD;
&#xD;
               -  Age &gt;= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for&#xD;
                  female&#xD;
&#xD;
          -  Patients with solid tumors: bilirubin (sum of conjugated + unconjugated) =&lt; 1.5 x&#xD;
             upper limit of normal (ULN) for age (within 7 days prior to enrollment)&#xD;
&#xD;
          -  Patients with solid tumors: serum glutamic pyruvic transaminase (SGPT) (alanine&#xD;
             aminotransferase [ALT]) =&lt; 135 U/L (within 7 days prior to enrollment); (for the&#xD;
             purpose of this study, the ULN for SGPT is 45 U/L)&#xD;
&#xD;
          -  Patients with solid tumors: serum albumin &gt;= 2 g/dL (within 7 days prior to&#xD;
             enrollment)&#xD;
&#xD;
          -  Activated partial thromboplastin time (aPTT) =&lt; 1.5 x ULN (within 7 days prior to&#xD;
             enrollment)&#xD;
&#xD;
          -  International normalized ratio (INR) =&lt; 1.5 (within 7 days prior to enrollment)&#xD;
&#xD;
          -  Patients must be able to swallow intact tablets&#xD;
&#xD;
          -  All patients and/or their parents or legally authorized representatives must sign a&#xD;
             written informed consent; assent, when appropriate, will be obtained according to&#xD;
             institutional guidelines&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breast-feeding women will not be entered on this study due to risks of&#xD;
             fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests&#xD;
             must be obtained in girls who are post-menarchal; women of child-bearing potential and&#xD;
             their partners should agree to use two (2) highly effective forms of contraception&#xD;
             throughout study participation and for at least one (1) month after the last dose of&#xD;
             olaparib; male study participants should avoid fathering a child or donating sperm&#xD;
             during the study and for three (3) months after the last dose of olaparib&#xD;
&#xD;
          -  Concomitant medications&#xD;
&#xD;
               -  Corticosteroids: patients receiving corticosteroids who have not been on a stable&#xD;
                  or decreasing dose of corticosteroid for at least 7 days prior to enrollment are&#xD;
                  not eligible; if used to modify immune adverse events related to prior therapy,&#xD;
                  &gt;= 14 days must have elapsed since last dose of corticosteroid&#xD;
&#xD;
               -  Investigational drugs: patients who are currently receiving another&#xD;
                  investigational drug are not eligible&#xD;
&#xD;
               -  Anti-cancer agents: patients who are currently receiving other anti-cancer agents&#xD;
                  are not eligible&#xD;
&#xD;
               -  Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,&#xD;
                  tacrolimus or other agents to prevent graft-versus-host disease post bone marrow&#xD;
                  transplant are not eligible for this trial&#xD;
&#xD;
               -  CYP3A/CYP3A4 agents: patients who are currently receiving drugs that are strong&#xD;
                  and moderate inducers or inhibitors of CYP3A or CYP3A4 are not eligible; strong&#xD;
                  inducers or inhibitors of CYP3A4 should be avoided from 21 days prior to&#xD;
                  enrollment to the end of the study&#xD;
&#xD;
          -  Patients who have an uncontrolled infection are not eligible&#xD;
&#xD;
          -  Patient who are known to be serologically positive for human immunodeficiency virus&#xD;
             (HIV)&#xD;
&#xD;
          -  Patients with known active hepatitis (i.e. hepatitis B or C)&#xD;
&#xD;
          -  Patients who have received a prior solid organ transplantation are not eligible&#xD;
&#xD;
          -  Patients with symptomatic uncontrolled brain metastases; a scan to confirm the absence&#xD;
             of brain metastases is not required; the patient can receive a stable dose of&#xD;
             corticosteroids before and during the study as long as these were started at least 4&#xD;
             weeks prior to enrollment; patients with spinal cord compression unless considered to&#xD;
             have received definitive treatment for this and evidence of clinically stable disease&#xD;
             for 28 days&#xD;
&#xD;
          -  Patients with known symptomatic Fanconi anemia (FA), ataxia-telangiectasia (A-T)&#xD;
             syndrome, Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are not eligible&#xD;
             (asymptomatic carriers are acceptable)&#xD;
&#xD;
          -  Major surgery must not have occurred within 2 weeks prior to enrollment and patients&#xD;
             must have recovered from any effects of any major surgery&#xD;
&#xD;
          -  Patients who in the opinion of the investigator may not be able to comply with the&#xD;
             safety monitoring requirements of the study are not eligible&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Months</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Julia Glade-Bender</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Oncology Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital of Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Alaska Medical Center</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Banner Children's at Desert</name>
      <address>
        <city>Mesa</city>
        <state>Arizona</state>
        <zip>85202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Banner University Medical Center - Tucson</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85719</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arkansas Children's Hospital</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72202-3591</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Downey Medical Center</name>
      <address>
        <city>Downey</city>
        <state>California</state>
        <zip>90242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Loma Linda University Medical Center</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <zip>92354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miller Children's and Women's Hospital Long Beach</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>
  </location>
  <location>
    <facility>
      <name>Valley Children's Hospital</name>
      <address>
        <city>Madera</city>
        <state>California</state>
        <zip>93636</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Benioff Children's Hospital Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center-Mission Bay</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alfred I duPont Hospital for Children</name>
      <address>
        <city>Wilmington</city>
        <state>Delaware</state>
        <zip>19803</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </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>
  </location>
  <location>
    <facility>
      <name>Nemours Children's Clinic-Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Miller School of Medicine-Sylvester Cancer Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nicklaus Children's Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33155</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AdventHealth Orlando</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arnold Palmer Hospital for Children</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemours Children's Hospital</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32827</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemours Children's Clinic - Pensacola</name>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <zip>32504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph's Hospital/Children's Hospital-Tampa</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta - Egleston</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Cancer Institute - Boise</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Comprehensive Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Jude Midwest Affiliate</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Illinois University School of Medicine</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riley Hospital for Children</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blank Children's Hospital</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa/Holden Comprehensive Cancer Center</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Children's Hospital</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital New Orleans</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Medical Center Jefferson</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eastern Maine Medical Center</name>
      <address>
        <city>Bangor</city>
        <state>Maine</state>
        <zip>04401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sinai Hospital of Baltimore</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21215</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </location>
  <location>
    <facility>
      <name>C S Mott Children's Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bronson Methodist Hospital</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospitals and Clinics of Minnesota - Minneapolis</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota/Masonic Cancer Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Mercy Hospitals and Clinics</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cardinal Glennon Children's Medical Center</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63104</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </location>
  <location>
    <facility>
      <name>Mercy Hospital Saint Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital and Medical Center of Omaha</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center of Southern Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alliance for Childhood Diseases/Cure 4 the Kids Foundation</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Summerlin Hospital Medical Center</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morristown Medical Center</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albany Medical Center</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</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>
    <facility>
      <name>NYU Winthrop Hospital</name>
      <address>
        <city>Mineola</city>
        <state>New York</state>
        <zip>11501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Steven and Alexandra Cohen Children's Medical Center of New York</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYP/Weill Cornell Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State University of New York Upstate Medical University</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Medical College</name>
      <address>
        <city>Valhalla</city>
        <state>New York</state>
        <zip>10595</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mission Hospital</name>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <zip>28801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolinas Medical Center/Levine Cancer Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novant Health Presbyterian Medical Center</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Broadway Medical Center</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </location>
  <location>
    <facility>
      <name>Dayton Children's Hospital</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Legacy Emanuel Children's Hospital</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97227</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </location>
  <location>
    <facility>
      <name>Geisinger Medical Center</name>
      <address>
        <city>Danville</city>
        <state>Pennsylvania</state>
        <zip>17822</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Pittsburgh of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prisma Health Richland Hospital</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BI-LO Charities Children's Cancer Center</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford USD Medical Center - Sioux Falls</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57117-5134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Tennessee Childrens Hospital</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37916</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University/Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dell Children's Medical Center of Central Texas</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78723</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical City Dallas Hospital</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern/Simmons Cancer Center-Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cook Children's Medical Center</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Methodist Children's Hospital of South Texas</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Health Science Center at San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scott and White Memorial Hospital</name>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <zip>76508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Primary Children's Hospital</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84113</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Vermont and State Agricultural College</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of The King's Daughters</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University/Massey Cancer Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Children's Hospital</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Sacred Heart Medical Center and Children's Hospital</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Madigan Army Medical Center</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98431</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Virginia University Healthcare</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Carbone Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Jorge Children's Hospital</name>
      <address>
        <city>San Juan</city>
        <zip>00912</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Pediatric Hospital</name>
      <address>
        <city>San Juan</city>
        <zip>00926</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Puerto Rico</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>July 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Glioma</mesh_term>
    <mesh_term>Neuroblastoma</mesh_term>
    <mesh_term>Neoplasms, Germ Cell and Embryonal</mesh_term>
    <mesh_term>Osteosarcoma</mesh_term>
    <mesh_term>Rhabdomyosarcoma</mesh_term>
    <mesh_term>Ependymoma</mesh_term>
    <mesh_term>Sarcoma, Ewing</mesh_term>
    <mesh_term>Medulloblastoma</mesh_term>
    <mesh_term>Neuroectodermal Tumors</mesh_term>
    <mesh_term>Neuroectodermal Tumors, Primitive</mesh_term>
    <mesh_term>Wilms Tumor</mesh_term>
    <mesh_term>Rhabdoid Tumor</mesh_term>
    <mesh_term>Neuroectodermal Tumors, Primitive, Peripheral</mesh_term>
    <mesh_term>Nervous System Neoplasms</mesh_term>
    <mesh_term>Hepatoblastoma</mesh_term>
    <mesh_term>Central Nervous System Neoplasms</mesh_term>
    <mesh_term>Histiocytosis, Langerhans-Cell</mesh_term>
    <mesh_term>Histiocytosis</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Olaparib</mesh_term>
    <mesh_term>Poly(ADP-ribose) Polymerase Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 9, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03233204/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03233204
org study id: NCI-2017-00766
secondary id: NCI-2017-00766
secondary id: APEC1621H
secondary id: APEC1621H
secondary id: APEC1621H
secondary id: U10CA180886
nct id: NCT03233204
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II Pediatric MATCH trial studies how well olaparib works in treating patients with
      solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with defects in deoxyribonucleic
      acid (DNA) damage repair genes that have spread to other places in the body (advanced) and
      have come back (relapsed) or do not respond to treatment (refractory). Olaparib is an
      inhibitor of PARP, an enzyme that helps repair DNA when it becomes damaged. Blocking PARP may
      help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors
      are a type of targeted therapy.
PRIMARY OBJECTIVE:

      I. To determine the objective response rate (ORR; complete response + partial response) in
      pediatric patients treated with olaparib with advanced solid tumors (including central
      nervous system [CNS] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor
      activating genetic alterations in the deleterious genetic alterations in the DNA damage
      repair (DDR) pathway.

      SECONDARY OBJECTIVES:

      I. To estimate the progression free survival in pediatric patients treated with olaparib with
      advanced solid tumors including non-Hodgkin lymphomas, CNS tumors, and histiocytosis that
      harbor deleterious genetic alterations in the DDR pathway.

      II. To obtain information about the tolerability of olaparib in children and adolescents with
      relapsed or refractory cancer.

      III. To provide preliminary estimates of the pharmacokinetics of olaparib in children and
      adolescents with relapsed or refractory cancer.

      EXPLORATORY OBJECTIVE:

      I. To explore approaches to profiling changes in tumor genomics over time through the
      evaluation of circulating tumor DNA.

      OUTLINE:

      Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28
      days for 2 years in the absence of disease progression or unacceptable toxicity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (complete response/partial response)
time frame: From enrollment to the end of treatment, up to 2 years
description: Determined using Response Evaluation Criteria in Solid Tumors version 1.1. A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method.
measure: Progression free survival (PFS)
time frame: From the initiation of protocol treatment to the occurrence of disease progression, disease recurrence, or death from any cause, assessed up to 4 years
description: PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
measure: Percentage of Patients Experiencing Grade 3 or Higher Adverse Events
time frame: From enrollment to 30 days after the end of treatment, up to 2 years
description: Percentage of patients experiencing grade 3 or higher adverse events will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All patients who receive at least one dose of protocol therapy will be considered in the evaluation of toxicity.
measure: Pharmacokinetics (PK) of olaparib
time frame: Pre-dose on day 1, and pre-dose, 1, 2, 4, and 6-8 hours after morning dose on day 8 of cycle 1
description: A descriptive analysis of PK parameters will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
measure: Change in tumor genomic profile
time frame: Cycle 5 day 1 to 4 years
description: Approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid will be explored. Descriptive analysis will be performed and will be summarized with simple summary statistics.
arm group label: Treatment (olaparib)
arm group type: Experimental
description: Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Olaparib
description: Given PO
arm group label: Treatment (olaparib)
other name: AZD 2281
other name: AZD-2281
other name: AZD2281
other name: KU-0059436
other name: Lynparza
other name: Olanib
other name: Olaparix
other name: PARP Inhibitor AZD2281
criteria: 
gender: All
minimum age: 12 Months
maximum age: 21 Years
healthy volunteers: No
last name: Julia Glade-Bender
role: Principal Investigator
affiliation: Children's Oncology Group
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country: Puerto Rico
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Neoplasms
mesh term: Sarcoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Glioma
mesh term: Neuroblastoma
mesh term: Neoplasms, Germ Cell and Embryonal
mesh term: Osteosarcoma
mesh term: Rhabdomyosarcoma
mesh term: Ependymoma
mesh term: Sarcoma, Ewing
mesh term: Medulloblastoma
mesh term: Neuroectodermal Tumors
mesh term: Neuroectodermal Tumors, Primitive
mesh term: Wilms Tumor
mesh term: Rhabdoid Tumor
mesh term: Neuroectodermal Tumors, Primitive, Peripheral
mesh term: Nervous System Neoplasms
mesh term: Hepatoblastoma
mesh term: Central Nervous System Neoplasms
mesh term: Histiocytosis, Langerhans-Cell
mesh term: Histiocytosis
mesh term: Recurrence
mesh term: Olaparib
mesh term: Poly(ADP-ribose) Polymerase Inhibitors
sharing ipd: Undecided
provided document: 