<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/NCT01721577</url>
  </required_header>
  <id_info>
    <org_study_id>11090804</org_study_id>
    <secondary_id>VABC; GCR</secondary_id>
    <nct_id>NCT01721577</nct_id>
  </id_info>
  <brief_title>Phase I/II Trial of AXL1717 in the Treatment of Recurrent Malignant Astrocytomas</brief_title>
  <acronym>AXL1717</acronym>
  <official_title>Phase I/II Clinical Trial of the Safety, Tolerability, and Anti-tumor Efficacy of the IGF-1R Inhibitor, AXL1717 (Picropodophyllin), in the Treatment of Recurrent Malignant Astrocytomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rush University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Axelar AB</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Rush University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single-center, open-label, non-randomized, Phase I/IIa study to investigate the&#xD;
      safety, tolerability, and antitumor efficacy of AXL1717 (picropodophyllin as active agent&#xD;
      formulated in an oral suspension; PPP) in patients with recurrent malignant astrocytomas&#xD;
      (glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic&#xD;
      oligoastrocytoma, and anaplastic ependymoma). Patients will be treated for up to 5 cycles. A&#xD;
      treatment cycle is defined as 28 days+7 days rest (28+7 days during cycle 1 to 4, and 28 days&#xD;
      during cycle 5). The following cycle will not be started until the treatment continuation&#xD;
      criteria are fulfilled. Concomitant supportive therapies will be allowed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      AXL1717, as a ready-to-use suspension of picropodophyllin for oral administration, will be&#xD;
      distributed in bottles for single use at a concentration of 25 mg/mL. Fixed doses will be&#xD;
      used, i.e. there are no adjustments for weight or body surface. There will be no&#xD;
      randomization or blinding in the study.&#xD;
&#xD;
      The trial will be divided in two phases. In the first phase, 10-20 patients will be enrolled&#xD;
      and treated with 300-520 mg BID of AXL1717 for 28 days. The primary endpoint of the first&#xD;
      phase is to determine the recommended Phase 2 dose (RP2D) of AXL1717 in patients with&#xD;
      recurrent or progressive glioblastoma and to assess the safety and toxicity of AXL1717 in&#xD;
      this patient population. The study has a 3+3 design and the first cohort will be treated with&#xD;
      400 mg AXL1717 BID for 28 days repeated in up to 5 cycles. If dose-limiting toxicity (DLT)&#xD;
      such as neutropenia occurs, dosing will be interrupted and the individual patient will,&#xD;
      following normalization, be restarted on the same or a lower dose level according to&#xD;
      standardized procedure. If two or three of the first 3 patients on a specific dose level&#xD;
      experience a DLT during the first 28 days of treatment with AXL1717, the following patients&#xD;
      will be treated with a lower dose level. If one DLT occurs during the first 28 days of dosing&#xD;
      in the first 3 three patients another 3 patients will be treated with the same dose level. If&#xD;
      2 of the 6 patients display DLT, the next patients will be treated with a lower dose level.&#xD;
      The highest dose level without DLT or with maximally one DLT out of 6 patients will be the&#xD;
      RPTD. All assessments with respect to dose adjustments for subsequent cohorts will be done&#xD;
      during the first 28 days of treatment. Non-progressing patients may be treated for a total of&#xD;
      five 28-day cycles (24 weeks).&#xD;
&#xD;
      In the second phase, 12 patients will be enrolled and treated with the identified RP2D of&#xD;
      AXL1717 for 28 days repeated in five cycles. The primary endpoints of phase II is to assess&#xD;
      the proportion of patients who are progression-free at 24 weeks and to assess safety,&#xD;
      tolerability, and adverse event profile of AXL1717.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Investigator went to another institution.&#xD;
  </why_stopped>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase I - Determine Recommended Phase II Dose</measure>
    <time_frame>8 months</time_frame>
    <description>To determine the recommended phase II dose (RPTD) of AXL1717 in recurrent malignant astrocytomas defined as the highest dose level without DLT (Dose Limiting Toxicity) or with maximally one DLT out of 6 patients will be the RPTD.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase II - To Determine if AXL1717 Has Any Antitumor Effect</measure>
    <time_frame>24 Weeks</time_frame>
    <description>To determine if AXL1717 has any antitumor effect as a single agent treatment in recurrent malignant astrocytomas by evaluating PFS at 24 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase I - To Identify the Maximum Tolerable Dose</measure>
    <time_frame>8 Months</time_frame>
    <description>To identify the Maximum Tolerated Dose (MTD) of AXL1717 in the Phase I subject population. MTD is the highest dose of AXL1717 with the lowest average per subject cases of DLT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase I - Molecular Markers of Optimum Response</measure>
    <time_frame>8 months</time_frame>
    <description>To assess potential molecular markers that might predict optimum response sub-population groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase I - Molecular Markers of IGF (Insulin Like Growth Factor)-1R Pathway</measure>
    <time_frame>8 months</time_frame>
    <description>To evaluate surrogate molecular markers of IGF-1R pathway activation/inhibition after treatment with AXL1717 in patients with malignant astrocytomas</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II - Time-To-Progression (TTP) and Overall Survival (OS)</measure>
    <time_frame>4 months</time_frame>
    <description>To determine time-to-progression (TTP) and overall survival (OS) of patients treated with AXL1717. Only overall survival for subjects is prolonged stable disease was analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II - Overall Response Rate</measure>
    <time_frame>4 months</time_frame>
    <description>To assess overall response rate (ORR) in recurrent malignant astrocytomas after treatment with AXL1717</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II - Identify Evidence of Response on Imaging</measure>
    <time_frame>8 Months</time_frame>
    <description>To identify surrogate imaging evidence of response on MRI sequences (especially T2- FLAIR, DWI, Perfusion MRI and multi-voxel MRS).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory Endpoint - Determine Antitumor Effect</measure>
    <time_frame>4 months</time_frame>
    <description>To assess the ability of AXL1717 to inhibit tumor proliferation as assessed by blood IGFBP-1 through IGFBP-7, growth hormone (GH) levels, C-peptide, IGF-1 (free and total), and IGF-2 levels, insulin, and analysis of tumor tissue of patients treated with AXL1717 for 5 days before surgical re-operation by examining for the IGF-1R signal transduction pathway in the resected brain tumor tissue, and correlate with outcome.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Glioblastoma</condition>
  <condition>Gliosarcoma</condition>
  <condition>Anaplastic Astrocytoma</condition>
  <condition>Anaplastic Oligodendroglioma</condition>
  <condition>Anaplastic Oligoastrocytoma</condition>
  <condition>Anaplastic Ependymoma</condition>
  <arm_group>
    <arm_group_label>Phase 1: AXL1717, 300mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the first phase, 10-20 patients will be enrolled and treated with 300mg (original range of starting dose was 300-520mg) BID of AXL1717 for 28 days. The primary endpoint of the first phase is to determine the recommended Phase 2 dose (RP2D) of AXL1717 and to assess the safety and toxicity of AXL1717. The study has a 3+3 design and the first cohort will be treated with 300 mg AXL1717 BID for 28 days repeated in up to 5 cycles. The highest dose level without DLT or with maximally one DLT out of 6 patients will be the RP2D. Non-progressing patients may be treated for a total of five 28-day cycles (24 weeks).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AXL1717</intervention_name>
    <description>IGF-1 receptor inhibitor</description>
    <arm_group_label>Phase 1: AXL1717, 300mg</arm_group_label>
    <other_name>picropodophyllin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          1. Be informed of the nature of the study and have provided written informed consent&#xD;
&#xD;
          2. At least 18 years of age&#xD;
&#xD;
          3. ECOG performance of 0, 1, or 2, or KPS (Karnofsky performance status) ≥ 60.&#xD;
&#xD;
          4. Pathological verification of a WHO grade 4 astrocytoma (glioblastoma or gliosarcoma),&#xD;
             or WHO Grade 3 anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic&#xD;
             oligoastrocytoma, or anaplastic ependymoma.&#xD;
&#xD;
          5. Documented recurrent glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic&#xD;
             oligodendroglioma, anaplastic oligoastrocytoma, or anaplastic ependymoma after at&#xD;
             least one failed treatment of chemotherapy and radiation&#xD;
&#xD;
          6. Expected survival of at least 3 months&#xD;
&#xD;
          7. At least 2-weeks from cytoreductive surgery, if performed, 4-weeks from bevacizumab or&#xD;
             other chemotherapy (6-weeks if prior chemotherapy was nitrosourea) and 12-weeks from&#xD;
             completion of radiotherapy.&#xD;
&#xD;
          8. Ability to undergo MRI scanning without and with imaging dye on a periodic basis as&#xD;
             defined in the protocol&#xD;
&#xD;
          9. Preserved major organ functions, i.e: Blood leukocyte count ≥ 3.0 x 109/L Blood&#xD;
             absolute neutrophil count ≥ 1.5 x 109/L Blood platelet count ≥ 100 x109/L Blood&#xD;
             hemoglobin ≥ 100 g/L (transfusions are allowed) Plasma total bilirubin level ≤ 1.5&#xD;
             times the upper institutional limit (ULN) of the ‖normal‖ (i.e. reference) range&#xD;
             Plasma AST (aspartate aminotransferase) or ALT ≤ 2.5 times upper institutional limit&#xD;
             (ULN) of the ‖normal‖ range Plasma creatinine ≤ 1.5 times upper institutional limit&#xD;
             (ULN) of the ‖normal‖ range 12-lead ECG with normal tracings; or changes that are not&#xD;
             clinically significant and do not require medical intervention, and QTc &lt; 500 ms At&#xD;
             least seven (7) days off of medications which inhibit or induce CYP2C9 or CYP3A4&#xD;
             before first study treatment day&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. Any or other major recent or ongoing disease that, according to the Investigator,&#xD;
             poses an unacceptable risk to the patient&#xD;
&#xD;
          2. Grade 3 or higher constipation within the past 28 days or grade 2 constipation within&#xD;
             the past 14 days before randomization. (Patients with grade 2 constipation within the&#xD;
             past 14 days could be re-screened if constipation decreases to ≤ grade 1 with optimal&#xD;
             management of constipation.)&#xD;
&#xD;
          3. Coexisting uncontrolled medical condition.&#xD;
&#xD;
          4. Hepatitis B or Hepatitis C, or HIV infection requiring anti-retroviral therapy&#xD;
&#xD;
          5. Active malignancy other than basal cell skin cancer&#xD;
&#xD;
          6. Other active malignancy during the previous 3 years&#xD;
&#xD;
          7. Major surgical procedure within 4 weeks&#xD;
&#xD;
          8. Prior stereotactic or gamma knife radiosurgery or proton radiation, unless unequivocal&#xD;
             progression by functional neuro-imaging (PET, dynamic MRI, MRS, SPECT) or by&#xD;
             re-operation with documented histologic confirmation of recurrence.&#xD;
&#xD;
          9. Prior anti-tumor therapy, as follows: at least 12-weeks from radiation therapy; at&#xD;
             least 4-weeks from prior treatment with temozolomide or bevacizumab, 6-weeks from BCNU&#xD;
             or CCNU.&#xD;
&#xD;
         10. Women of child bearing potential (WOCBP) who do not consent to using acceptable&#xD;
             methods of birth control (oral contraceptives, IUD). For purposes of this study, WOCBP&#xD;
             include any female who has experienced menarche, who has not undergone tubal ligation,&#xD;
             and who is not postmenopausal.&#xD;
&#xD;
         11. Medically uncontrolled Type 1 or Type 2 diabetes mellitus&#xD;
&#xD;
         12. Pregnancy or lactation&#xD;
&#xD;
         13. Current participation in any other investigational clinical trial within 4-weeks.&#xD;
&#xD;
         14. Eastern Cooperative Oncology Group (ECOG) performance status &gt; 2 after optimization of&#xD;
             medications (See Appendix 4) or KPS &lt; 60&#xD;
&#xD;
         15. Anticipated Life expectancy less than 3 months&#xD;
&#xD;
         16. Contraindications to the investigational product or known or suspected&#xD;
             hypersensitivity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert Aiken, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rush University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G, Baserga R, Iliakis G, Aiken RD. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol. 2001 Apr 15;19(8):2189-200. doi: 10.1200/JCO.2001.19.8.2189.</citation>
    <PMID>11304771</PMID>
  </reference>
  <reference>
    <citation>Girnita A, Girnita L, del Prete F, Bartolazzi A, Larsson O, Axelson M. Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth. Cancer Res. 2004 Jan 1;64(1):236-42. doi: 10.1158/0008-5472.can-03-2522.</citation>
    <PMID>14729630</PMID>
  </reference>
  <reference>
    <citation>Ekman S, Frodin JE, Harmenberg J, Bergman A, Hedlund A, Dahg P, Alvfors C, Stahl B, Bergstrom S, Bergqvist M. Clinical Phase I study with an Insulin-like Growth Factor-1 receptor inhibitor: experiences in patients with squamous non-small cell lung carcinoma. Acta Oncol. 2011 Apr;50(3):441-7. doi: 10.3109/0284186X.2010.499370. Epub 2010 Aug 11.</citation>
    <PMID>20698809</PMID>
  </reference>
  <reference>
    <citation>Yin S, Girnita A, Stromberg T, Khan Z, Andersson S, Zheng H, Ericsson C, Axelson M, Nister M, Larsson O, Ekstrom TJ, Girnita L. Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma. Neuro Oncol. 2010 Jan;12(1):19-27. doi: 10.1093/neuonc/nop008. Epub 2009 Oct 20.</citation>
    <PMID>20150364</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>October 29, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 4, 2012</study_first_posted>
  <results_first_submitted>October 13, 2021</results_first_submitted>
  <results_first_submitted_qc>April 26, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">May 22, 2023</results_first_posted>
  <last_update_submitted>April 26, 2023</last_update_submitted>
  <last_update_submitted_qc>April 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>glioblastoma</keyword>
  <keyword>gliosarcoma</keyword>
  <keyword>anaplastic astrocytoma</keyword>
  <keyword>anaplastic oligodendroglioma</keyword>
  <keyword>anaplastic oligoastrocytoma</keyword>
  <keyword>AXL1717</keyword>
  <keyword>IGF-1 receptor inhibitor</keyword>
  <keyword>picropodophyllin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
    <mesh_term>Astrocytoma</mesh_term>
    <mesh_term>Ependymoma</mesh_term>
    <mesh_term>Gliosarcoma</mesh_term>
    <mesh_term>Oligodendroglioma</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>One patient was excluded from the study after screening but before treatment and is not considered in this analysis.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>AXL1717 400mg BID</title>
          <description>Started on 400mg BID</description>
        </group>
        <group group_id="P2">
          <title>AXL1717 300mg BID</title>
          <description>Started on 300mg BID</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Dose Escalation to 400mg BID</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>AXL1717, 400mg Initial Dose</title>
          <description>Subjects who started and completed the study on 400mg BID</description>
        </group>
        <group group_id="B2">
          <title>AXL1717, 300mg Initial Dose</title>
          <description>Subjects who started the study on 300mg BID. one subject was escalated to 400mg BID and 2 subjects were de-escalated to 215mg BID</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58" lower_limit="57" upper_limit="59"/>
                    <measurement group_id="B2" value="56.2" lower_limit="37" upper_limit="69"/>
                    <measurement group_id="B3" value="56.6" lower_limit="37" upper_limit="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase I - Determine Recommended Phase II Dose</title>
        <description>To determine the recommended phase II dose (RPTD) of AXL1717 in recurrent malignant astrocytomas defined as the highest dose level without DLT (Dose Limiting Toxicity) or with maximally one DLT out of 6 patients will be the RPTD.</description>
        <time_frame>8 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Study Participants</title>
            <description>All study participants who received different doses of the same formulation of AXL1717.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I - Determine Recommended Phase II Dose</title>
          <description>To determine the recommended phase II dose (RPTD) of AXL1717 in recurrent malignant astrocytomas defined as the highest dose level without DLT (Dose Limiting Toxicity) or with maximally one DLT out of 6 patients will be the RPTD.</description>
          <units>MG</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">No dose in the trial met this criteria for establishing a RPTD.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase II - To Determine if AXL1717 Has Any Antitumor Effect</title>
        <description>To determine if AXL1717 has any antitumor effect as a single agent treatment in recurrent malignant astrocytomas by evaluating PFS at 24 weeks</description>
        <time_frame>24 Weeks</time_frame>
        <population>Phase II of this study was never initiated and so no data was collected or analyzed for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase II Subject Group</title>
            <description>This group was never established as Phase I of the study was never completed and thus Phase II was never initiated.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II - To Determine if AXL1717 Has Any Antitumor Effect</title>
          <description>To determine if AXL1717 has any antitumor effect as a single agent treatment in recurrent malignant astrocytomas by evaluating PFS at 24 weeks</description>
          <population>Phase II of this study was never initiated and so no data was collected or analyzed for this endpoint.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase I - To Identify the Maximum Tolerable Dose</title>
        <description>To identify the Maximum Tolerated Dose (MTD) of AXL1717 in the Phase I subject population. MTD is the highest dose of AXL1717 with the lowest average per subject cases of DLT.</description>
        <time_frame>8 Months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Study Participants</title>
            <description>All study participants who received different doses of the same formulation of AXL1717.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I - To Identify the Maximum Tolerable Dose</title>
          <description>To identify the Maximum Tolerated Dose (MTD) of AXL1717 in the Phase I subject population. MTD is the highest dose of AXL1717 with the lowest average per subject cases of DLT.</description>
          <units>MG</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="300"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase I - Molecular Markers of Optimum Response</title>
        <description>To assess potential molecular markers that might predict optimum response sub-population groups</description>
        <time_frame>8 months</time_frame>
        <population>the data for this outcome measure was not collected and/or analyzed. There is no data to report.</population>
        <group_list>
          <group group_id="O1">
            <title>AXL1717</title>
            <description>All subject who participated in the study and received at least one cycle of treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I - Molecular Markers of Optimum Response</title>
          <description>To assess potential molecular markers that might predict optimum response sub-population groups</description>
          <population>the data for this outcome measure was not collected and/or analyzed. There is no data to report.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase I - Molecular Markers of IGF (Insulin Like Growth Factor)-1R Pathway</title>
        <description>To evaluate surrogate molecular markers of IGF-1R pathway activation/inhibition after treatment with AXL1717 in patients with malignant astrocytomas</description>
        <time_frame>8 months</time_frame>
        <population>None of the secondary outcome measures were collected or analyzed as this study was conducted using the oral suspension of AXL1717 and there is a new formulation of AXL1717 in development (capsule). Decision was made to abandon other analysis or data collections in regards to secondary outcomes.</population>
        <group_list>
          <group group_id="O1">
            <title>AXL1717, 400mg Initial Does</title>
            <description>first 2 subjects were started on 400mg BID initial dose.</description>
          </group>
          <group group_id="O2">
            <title>AXL1717, 300mg Initial Does</title>
            <description>Subjects who were started on 300mg BID</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I - Molecular Markers of IGF (Insulin Like Growth Factor)-1R Pathway</title>
          <description>To evaluate surrogate molecular markers of IGF-1R pathway activation/inhibition after treatment with AXL1717 in patients with malignant astrocytomas</description>
          <population>None of the secondary outcome measures were collected or analyzed as this study was conducted using the oral suspension of AXL1717 and there is a new formulation of AXL1717 in development (capsule). Decision was made to abandon other analysis or data collections in regards to secondary outcomes.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase II - Time-To-Progression (TTP) and Overall Survival (OS)</title>
        <description>To determine time-to-progression (TTP) and overall survival (OS) of patients treated with AXL1717. Only overall survival for subjects is prolonged stable disease was analyzed.</description>
        <time_frame>4 months</time_frame>
        <population>Phase II of this study was never initiated and so no data was collected or analyzed for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase II Study Population</title>
            <description>This group was never established as Phase I of the study was never completed and thus Phase II was never initiated.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II - Time-To-Progression (TTP) and Overall Survival (OS)</title>
          <description>To determine time-to-progression (TTP) and overall survival (OS) of patients treated with AXL1717. Only overall survival for subjects is prolonged stable disease was analyzed.</description>
          <population>Phase II of this study was never initiated and so no data was collected or analyzed for this endpoint.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase II - Overall Response Rate</title>
        <description>To assess overall response rate (ORR) in recurrent malignant astrocytomas after treatment with AXL1717</description>
        <time_frame>4 months</time_frame>
        <population>Phase II of the study was never initiated. No data was gathered or analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase II Study Population</title>
            <description>This group was never established as Phase I of the study was never completed and thus Phase II was never initiated.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II - Overall Response Rate</title>
          <description>To assess overall response rate (ORR) in recurrent malignant astrocytomas after treatment with AXL1717</description>
          <population>Phase II of the study was never initiated. No data was gathered or analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase II - Identify Evidence of Response on Imaging</title>
        <description>To identify surrogate imaging evidence of response on MRI sequences (especially T2- FLAIR, DWI, Perfusion MRI and multi-voxel MRS).</description>
        <time_frame>8 Months</time_frame>
        <population>Phase II of the study was never initiated.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase II Subject Group</title>
            <description>This group was never established as Phase I of the study was never completed and thus Phase II was never initiated.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II - Identify Evidence of Response on Imaging</title>
          <description>To identify surrogate imaging evidence of response on MRI sequences (especially T2- FLAIR, DWI, Perfusion MRI and multi-voxel MRS).</description>
          <population>Phase II of the study was never initiated.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Exploratory Endpoint - Determine Antitumor Effect</title>
        <description>To assess the ability of AXL1717 to inhibit tumor proliferation as assessed by blood IGFBP-1 through IGFBP-7, growth hormone (GH) levels, C-peptide, IGF-1 (free and total), and IGF-2 levels, insulin, and analysis of tumor tissue of patients treated with AXL1717 for 5 days before surgical re-operation by examining for the IGF-1R signal transduction pathway in the resected brain tumor tissue, and correlate with outcome.</description>
        <time_frame>4 months</time_frame>
        <population>Phase II portion of this study was not initiated as the phase 1 piece was not completed fully. This endpoint was not explored and data was not collected or analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>AXL1717, 400mg Initial Dose</title>
            <description>Subjects who started and completed the study on 400mg BID</description>
          </group>
          <group group_id="O2">
            <title>AXL1717, 300mg Initial Dose</title>
            <description>Subjects who started the study on 300mg BID. one subject was escalated to 400mg BID and 2 subjects were de-escalated to 215mg BID</description>
          </group>
        </group_list>
        <measure>
          <title>Exploratory Endpoint - Determine Antitumor Effect</title>
          <description>To assess the ability of AXL1717 to inhibit tumor proliferation as assessed by blood IGFBP-1 through IGFBP-7, growth hormone (GH) levels, C-peptide, IGF-1 (free and total), and IGF-2 levels, insulin, and analysis of tumor tissue of patients treated with AXL1717 for 5 days before surgical re-operation by examining for the IGF-1R signal transduction pathway in the resected brain tumor tissue, and correlate with outcome.</description>
          <population>Phase II portion of this study was not initiated as the phase 1 piece was not completed fully. This endpoint was not explored and data was not collected or analyzed</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Phase I Subjects - Imaging Evidence of Response.</title>
        <description>Number of Participants with Imaging Evidence of Response on MRI (magnetic resonance imaging)sequences by RANO criteria (with additional special attention to T2-FLAIR, DWI (diffusion-weighted imaging), perfusion MRI and multi-voxel MRS (magnetic resonance spectroscopy) sequences).</description>
        <time_frame>4 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>AXL1717, 400mg Initial Dose</title>
            <description>Subjects who were started on 400mg initial dose</description>
          </group>
          <group group_id="O2">
            <title>AXL1717, 300mg Initial Dose</title>
            <description>Subjects who were started on 300mg initial dose</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I Subjects - Imaging Evidence of Response.</title>
          <description>Number of Participants with Imaging Evidence of Response on MRI (magnetic resonance imaging)sequences by RANO criteria (with additional special attention to T2-FLAIR, DWI (diffusion-weighted imaging), perfusion MRI and multi-voxel MRS (magnetic resonance spectroscopy) sequences).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>information was collected for each subject while on study (~some were up to 1 year)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>400mg BID</title>
          <description>Subjects on 400mg BID of AXL1717</description>
        </group>
        <group group_id="E2">
          <title>300mg BID</title>
          <description>Subjects on 300mg BID of AXL1717</description>
        </group>
        <group group_id="E3">
          <title>215mg BID</title>
          <description>Subjects on 215mg BID of AXL1717</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Paresthesias</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>I am not privvy to all the agreements that exist. But the original PI left the institution where this study was conducted, and he left with a separation agreement in place. I (Crista Brawley) am named in that agreement. Please direct questions to Dr. Robert Aiken.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Crista Brawley</name_or_title>
      <organization>Rush University Medical Center</organization>
      <phone>312-563-2312</phone>
      <email>crista_brawley@rush.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01721577
org study id: 11090804
secondary id: VABC; GCR
nct id: NCT01721577
lead sponsor: 
collaborator: 
has dmc: Yes
This is a single-center, open-label, non-randomized, Phase I/IIa study to investigate the
      safety, tolerability, and antitumor efficacy of AXL1717 (picropodophyllin as active agent
      formulated in an oral suspension; PPP) in patients with recurrent malignant astrocytomas
      (glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic
      oligoastrocytoma, and anaplastic ependymoma). Patients will be treated for up to 5 cycles. A
      treatment cycle is defined as 28 days+7 days rest (28+7 days during cycle 1 to 4, and 28 days
      during cycle 5). The following cycle will not be started until the treatment continuation
      criteria are fulfilled. Concomitant supportive therapies will be allowed.
AXL1717, as a ready-to-use suspension of picropodophyllin for oral administration, will be
      distributed in bottles for single use at a concentration of 25 mg/mL. Fixed doses will be
      used, i.e. there are no adjustments for weight or body surface. There will be no
      randomization or blinding in the study.

      The trial will be divided in two phases. In the first phase, 10-20 patients will be enrolled
      and treated with 300-520 mg BID of AXL1717 for 28 days. The primary endpoint of the first
      phase is to determine the recommended Phase 2 dose (RP2D) of AXL1717 in patients with
      recurrent or progressive glioblastoma and to assess the safety and toxicity of AXL1717 in
      this patient population. The study has a 3+3 design and the first cohort will be treated with
      400 mg AXL1717 BID for 28 days repeated in up to 5 cycles. If dose-limiting toxicity (DLT)
      such as neutropenia occurs, dosing will be interrupted and the individual patient will,
      following normalization, be restarted on the same or a lower dose level according to
      standardized procedure. If two or three of the first 3 patients on a specific dose level
      experience a DLT during the first 28 days of treatment with AXL1717, the following patients
      will be treated with a lower dose level. If one DLT occurs during the first 28 days of dosing
      in the first 3 three patients another 3 patients will be treated with the same dose level. If
      2 of the 6 patients display DLT, the next patients will be treated with a lower dose level.
      The highest dose level without DLT or with maximally one DLT out of 6 patients will be the
      RPTD. All assessments with respect to dose adjustments for subsequent cohorts will be done
      during the first 28 days of treatment. Non-progressing patients may be treated for a total of
      five 28-day cycles (24 weeks).

      In the second phase, 12 patients will be enrolled and treated with the identified RP2D of
      AXL1717 for 28 days repeated in five cycles. The primary endpoints of phase II is to assess
      the proportion of patients who are progression-free at 24 weeks and to assess safety,
      tolerability, and adverse event profile of AXL1717.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase I - Determine Recommended Phase II Dose
time frame: 8 months
description: To determine the recommended phase II dose (RPTD) of AXL1717 in recurrent malignant astrocytomas defined as the highest dose level without DLT (Dose Limiting Toxicity) or with maximally one DLT out of 6 patients will be the RPTD.
measure: Phase II - To Determine if AXL1717 Has Any Antitumor Effect
time frame: 24 Weeks
description: To determine if AXL1717 has any antitumor effect as a single agent treatment in recurrent malignant astrocytomas by evaluating PFS at 24 weeks
measure: Phase I - To Identify the Maximum Tolerable Dose
time frame: 8 Months
description: To identify the Maximum Tolerated Dose (MTD) of AXL1717 in the Phase I subject population. MTD is the highest dose of AXL1717 with the lowest average per subject cases of DLT.
measure: Phase I - Molecular Markers of Optimum Response
time frame: 8 months
description: To assess potential molecular markers that might predict optimum response sub-population groups
measure: Phase I - Molecular Markers of IGF (Insulin Like Growth Factor)-1R Pathway
time frame: 8 months
description: To evaluate surrogate molecular markers of IGF-1R pathway activation/inhibition after treatment with AXL1717 in patients with malignant astrocytomas
measure: Phase II - Time-To-Progression (TTP) and Overall Survival (OS)
time frame: 4 months
description: To determine time-to-progression (TTP) and overall survival (OS) of patients treated with AXL1717. Only overall survival for subjects is prolonged stable disease was analyzed.
measure: Phase II - Overall Response Rate
time frame: 4 months
description: To assess overall response rate (ORR) in recurrent malignant astrocytomas after treatment with AXL1717
measure: Phase II - Identify Evidence of Response on Imaging
time frame: 8 Months
description: To identify surrogate imaging evidence of response on MRI sequences (especially T2- FLAIR, DWI, Perfusion MRI and multi-voxel MRS).
measure: Exploratory Endpoint - Determine Antitumor Effect
time frame: 4 months
description: To assess the ability of AXL1717 to inhibit tumor proliferation as assessed by blood IGFBP-1 through IGFBP-7, growth hormone (GH) levels, C-peptide, IGF-1 (free and total), and IGF-2 levels, insulin, and analysis of tumor tissue of patients treated with AXL1717 for 5 days before surgical re-operation by examining for the IGF-1R signal transduction pathway in the resected brain tumor tissue, and correlate with outcome.
arm group label: Phase 1: AXL1717, 300mg
arm group type: Experimental
description: In the first phase, 10-20 patients will be enrolled and treated with 300mg (original range of starting dose was 300-520mg) BID of AXL1717 for 28 days. The primary endpoint of the first phase is to determine the recommended Phase 2 dose (RP2D) of AXL1717 and to assess the safety and toxicity of AXL1717. The study has a 3+3 design and the first cohort will be treated with 300 mg AXL1717 BID for 28 days repeated in up to 5 cycles. The highest dose level without DLT or with maximally one DLT out of 6 patients will be the RP2D. Non-progressing patients may be treated for a total of five 28-day cycles (24 weeks).
intervention type: Drug
intervention name: AXL1717
description: IGF-1 receptor inhibitor
arm group label: Phase 1: AXL1717, 300mg
other name: picropodophyllin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Robert Aiken, MD
role: Principal Investigator
affiliation: Rush University Medical Center
facility: 
country: United States
citation: Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G, Baserga R, Iliakis G, Aiken RD. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol. 2001 Apr 15;19(8):2189-200. doi: 10.1200/JCO.2001.19.8.2189.
PMID: 11304771
citation: Girnita A, Girnita L, del Prete F, Bartolazzi A, Larsson O, Axelson M. Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth. Cancer Res. 2004 Jan 1;64(1):236-42. doi: 10.1158/0008-5472.can-03-2522.
PMID: 14729630
citation: Ekman S, Frodin JE, Harmenberg J, Bergman A, Hedlund A, Dahg P, Alvfors C, Stahl B, Bergstrom S, Bergqvist M. Clinical Phase I study with an Insulin-like Growth Factor-1 receptor inhibitor: experiences in patients with squamous non-small cell lung carcinoma. Acta Oncol. 2011 Apr;50(3):441-7. doi: 10.3109/0284186X.2010.499370. Epub 2010 Aug 11.
PMID: 20698809
citation: Yin S, Girnita A, Stromberg T, Khan Z, Andersson S, Zheng H, Ericsson C, Axelson M, Nister M, Larsson O, Ekstrom TJ, Girnita L. Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma. Neuro Oncol. 2010 Jan;12(1):19-27. doi: 10.1093/neuonc/nop008. Epub 2009 Oct 20.
PMID: 20150364
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Astrocytoma
mesh term: Ependymoma
mesh term: Gliosarcoma
mesh term: Oligodendroglioma
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 