<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/NCT03008148</url>
  </required_header>
  <id_info>
    <org_study_id>JP001-GM-001</org_study_id>
    <nct_id>NCT03008148</nct_id>
  </id_info>
  <brief_title>Phase II/III Trial of CCRT With or Without JP001 for Newly Diagnosed GBM</brief_title>
  <official_title>Randomized Phase II/III Trial of Radiotherapy Plus Concomitant and Adjuvant Temozolomide With or Without Hydroxychloroquine, Rapamycin for Newly Diagnosed Glioblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johnpro Biotech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johnpro Biotech, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center, phase II/III, open-label, randomized, parallel and standard&#xD;
      chemoradiation-controlled study where eligible subjects will be randomized at 1:1 ratio to&#xD;
      receive control treatment or study treatment. The primary objective of this trial is to&#xD;
      evaluate the effect of add-on JP001 to standard chemoradiation in increasing overall survival&#xD;
      (OS) on newly diagnosed glioblastoma (GBM) patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After enrollment, subjects' previous tumor block used for glioblastoma diagnosis that is&#xD;
      consented to provide during the study period will be sent to a central laboratory for the&#xD;
      assessment of MGMT status. Moreover, subjects will be randomized in either Control or Study&#xD;
      arm at Visit 2. Subjects in Control arm will receive a standard chemoradiation. However,&#xD;
      subjects in Study arm will receive a standard chemoradiation in combination with concurrent&#xD;
      JP001 in whole study period. During the study, a sufficient amount of investigational&#xD;
      products will be supplied to subjects in study groups until next scheduled visits. Subjects&#xD;
      will self-administer investigational product orally with water at approximately the same time&#xD;
      in each day. Subjects should fast for a minimum of 2 hours prior to any doses of JP001 and/or&#xD;
      Temozolomide and then fast for another 1 hour after taking JP001 and/or Temozolomide. During&#xD;
      and at the end of treatment, subjects will be evaluated for efficacy and safety parameters.&#xD;
      Moreover, there will be a Follow-up visit for safety 4 weeks after the End-of-Treatment&#xD;
      visit. If a subject is early withdrawn from the study, the End-of-Treatment visit should be&#xD;
      arranged and all assessments assigned in this visit should be performed. The Safety Follow-up&#xD;
      visit for early withdrawn subjects could be either clinic visit or telephone contact. If&#xD;
      withdrawn subjects refuse to perform Follow-up visit, the Follow-up visit is allowed to&#xD;
      cancel. For subjects who completed or discontinued study treatment, assessment of survival&#xD;
      status will be performed every 8 weeks by telephone contact until death, study end (last&#xD;
      subject last visit; the last subject needs to be followed at least 30 months), or study&#xD;
      termination by Sponsor. Survival information will be recorded in the medical source and CRF.&#xD;
      If subjects are lost to follow-up or refuse to receive the assessment of survival status, the&#xD;
      investigator will record the last date subjects known to be alive in the medical source and&#xD;
      case report form.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 11, 2018</start_date>
  <completion_date type="Anticipated">April 2025</completion_date>
  <primary_completion_date type="Anticipated">April 2025</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival time.</measure>
    <time_frame>120 weeks</time_frame>
    <description>All subjects will be followed until study end (the date of last subject last visit; the last subject need to be followed at least 30 months) or death, whichever comes first; OS defined as the time from the date of Randomization to the date of death or last follow-up.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival time</measure>
    <time_frame>120 weeks</time_frame>
    <description>All subjects will be followed until study end or disease progression confirmed, whichever comes first; PFS defined as the time from the date of Randomization to the date of disease progression, death or last follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS rate at 1 year.</measure>
    <time_frame>1 year</time_frame>
    <description>OS defined as the time from the date of Randomization to the date of death or last follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS rate at 1 year.</measure>
    <time_frame>1 year</time_frame>
    <description>PFS defined as the time from the date of Randomization to the date of disease progression, death or last follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The time and rate of OS in different RPA class.</measure>
    <time_frame>120 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The time and rate of PFS in different RPA class.</measure>
    <time_frame>120 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate.</measure>
    <time_frame>120 weeks</time_frame>
    <description>Defined as the proportion of subjects who were confirmed completed response or partial response determined by RANO criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in score of EORTC QLQ-C30</measure>
    <time_frame>120 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in score of EORTC QLQ-BN20.</measure>
    <time_frame>120 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in grade of ECOG performance status.</measure>
    <time_frame>120 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">288</enrollment>
  <condition>Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Radiation,Temozolomide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>CCRT Phase: Radiation(60 Gy in 2 Gy/fx) + daily Temozolomide (75 mg/m²/day for 6 weeks).&#xD;
Rest Phase: Rest for 4 weeks.&#xD;
Chemotherapy Phase: Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles.&#xD;
Maintenance Phase: No maintenance treatment until disease progression confirmed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Radiation,Temozolomide,Siroquine(JP001)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CCRT Phase: Radiation(60 Gy in 2 Gy/fx) + daily Temozolomide (75 mg/m²/day for 6 weeks) + Daily JP001 (2 tablets once a day for 6 weeks).&#xD;
Rest Phase: Daily JP001(2 tablets/day) for 4 weeks.&#xD;
Chemotherapy Phase: Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles + Daily JP001(2 tablets once a day) for 24 weeks (4 weeks for each cycle).&#xD;
Maintenance Phase: JP001(2 tablets once a day) until disease progression confirmed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>CCRT</intervention_name>
    <description>CCRT Phase: Radiation(60 Gy in 2 Gy/fx) + daily Temozolomide (75 mg/m²/day for 6 weeks).</description>
    <arm_group_label>Radiation,Temozolomide</arm_group_label>
    <arm_group_label>Radiation,Temozolomide,Siroquine(JP001)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles.</description>
    <arm_group_label>Radiation,Temozolomide</arm_group_label>
    <arm_group_label>Radiation,Temozolomide,Siroquine(JP001)</arm_group_label>
    <other_name>Chemotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Siroquine</intervention_name>
    <description>Chemotherapy Phase: Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles + Daily JP001(2 tablets once a day) for 24 weeks (4 weeks for each cycle).&#xD;
Maintenance Phase: JP001(2 tablets once a day) until disease progression confirmed.</description>
    <arm_group_label>Radiation,Temozolomide,Siroquine(JP001)</arm_group_label>
    <other_name>JP001</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects with histologically proven newly diagnosed case of GBM (WHO grade IV) and&#xD;
             treatment-naive (chemotherapy and radiotherapy) for GBM. Diagnosis must be made by&#xD;
             stereotactic biopsy or surgical excision, either partial or complete within 3 months&#xD;
             prior to Visit 1.&#xD;
&#xD;
          2. Subject's RPA class is class III, IV or V.&#xD;
&#xD;
          3. Subjects with stereotactic biopsy or brain surgery must be suited for or will be&#xD;
             scheduled for CCRT followed by Temozolomide treatment, the standard treatment&#xD;
             recommended by institutes and fulfilled the reimbursement guideline of National Health&#xD;
             Insurance Administration.&#xD;
&#xD;
          4. Subjects must have recovered from the effects of surgery, post-operative infection,&#xD;
             and other complications prior to Visit 1. Study treatment must be performed &gt; 3 weeks&#xD;
             and ≤ 8 weeks after craniotomy. Ventricular fluid reservoir or Ventriculo-Peritoneal&#xD;
             shunting tube is allowed to keep.&#xD;
&#xD;
          5. A diagnostic contrast-enhanced MRI of the brain must be performed postoperatively&#xD;
             within 28 days prior to Visit 2 (Day 1).&#xD;
&#xD;
          6. ECOG performance status ≤ 3 at Visit 1.&#xD;
&#xD;
          7. Age from 20 to 80 years old at Visit 1.&#xD;
&#xD;
          8. Life expectation ≥ 12 weeks at Visit 1.&#xD;
&#xD;
          9. CBC/differential obtained at Visit 1, with adequate bone marrow function defined as&#xD;
             follows:&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 (1.5 x 109/L) or white blood&#xD;
                  cell (WBC) ≥ 3,000 cells/mm3 (3 x 109/L).&#xD;
&#xD;
               2. Platelets count ≥ 100,000 cells/mm3 (100 x 109/L).&#xD;
&#xD;
               3. Hemoglobin (Hgb or Hb) ≥ 10.0 g/dL (100 g/L) (Note: The use of transfusion or&#xD;
                  other intervention to achieve Hemoglobin ≥ 10.0 g/dL (100 g/L) is acceptable).&#xD;
&#xD;
         10. Adequate renal function, as defined below:&#xD;
&#xD;
             a. Creatinine ≤ 1.5 times upper laboratory limit at Visit 1.&#xD;
&#xD;
         11. Adequate hepatic function, as defined below:&#xD;
&#xD;
               1. Total Bilirubin ≤ 2.0 mg/dL (34.20 umol/L) at Visit 1.&#xD;
&#xD;
               2. ALT ≤ 3 times upper laboratory limit at Visit 1.&#xD;
&#xD;
               3. AST ≤ 3 times upper laboratory limit at Visit 1.&#xD;
&#xD;
         12. Subjects is able to understand and willing to comply with the study procedures and has&#xD;
             signed the informed consent form (ICF).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Other invasive malignancy. However, subject with other invasive malignancy that have&#xD;
             been disease-free more than or equal to 10 years and deemed no need for anti-cancer&#xD;
             treatments can be recruited. Subjects with noninvasive malignancy, including carcinoma&#xD;
             in situ of the breast, non-melanomatous skin cancer and cervix carcinoma in situ can&#xD;
             be recruited if disease-free and treatment free more than or equal to 3 years.&#xD;
&#xD;
          2. Metastases detected beyond the cranial vault.&#xD;
&#xD;
          3. Subjects with the following history:&#xD;
&#xD;
               1. Brain irradiation or Temozolomide usage.&#xD;
&#xD;
               2. Macular degeneration or retinopathy.&#xD;
&#xD;
               3. Renal transplantation.&#xD;
&#xD;
          4. Subjects are currently receiving any anti-rejection medicine or Hydroxychloroquine&#xD;
             sulfate for rheumatoid arthritis.&#xD;
&#xD;
          5. Subjects with severe and active co-morbidity, defined as follows:&#xD;
&#xD;
               1. Clinical active kidney, liver, lung or cardiac disease.&#xD;
&#xD;
               2. Acute bacterial or fungal infection requiring intravenous antibiotics at Visit 1&#xD;
                  and acquired immune deficiency syndrome (AIDS).&#xD;
&#xD;
               3. Any active infection or uncontrolled infection at Visit 1.&#xD;
&#xD;
               4. Abnormal CXR finding with risks of infection and interstitial lung&#xD;
                  disease/pneumonitis.&#xD;
&#xD;
          6. Pregnant or lactating women, due to possible adverse effects on the developing fetus&#xD;
             or infant from study drug.&#xD;
&#xD;
          7. Mean QTc &gt; 500 msec (with Bazett's correction), history of familial long QT syndrome&#xD;
             or other significant ECG abnormality noted at Visit 1.&#xD;
&#xD;
          8. Known hypersensitivity reactions to Temozolomide, dacarbazine (DTIC),&#xD;
             hydroxychloroquine, 4-aminoquinoline, rapamune, sirolimus, rapamycin, or their&#xD;
             analogs.&#xD;
&#xD;
          9. Women of child-bearing potential or men who are able to father a child unwilling to&#xD;
             use a. medically acceptable method of contraception during the trial.&#xD;
&#xD;
         10. Subjects participated in another investigational agent study in the past 30 days or&#xD;
             are planning to do so during the study period.&#xD;
&#xD;
         11. Subjects are considered ineligible for the study as judged by the investigator.&#xD;
&#xD;
         12. Subjects with positive HBsAg or positive anti-HCV.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Kwan-Hwa Chi</last_name>
    <phone>886-2-28332211</phone>
    <phone_ext>2274</phone_ext>
    <email>M006565@ms.skh.org.tw</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Susan Huang</last_name>
    <phone>886-2-28332211</phone>
    <phone_ext>2612</phone_ext>
    <email>susan.huang@johnpro.com.tw</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei City</city>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Yu-Ming Liu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Tri-Service General Hospital</name>
      <address>
        <city>Taipei City</city>
        <zip>11490</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Hsin-I Ma</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>December 23, 2016</study_first_submitted>
  <study_first_submitted_qc>December 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>May 10, 2021</last_update_submitted>
  <last_update_submitted_qc>May 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2021</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>Glioblastoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03008148
org study id: JP001-GM-001
nct id: NCT03008148
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a multi-center, phase II/III, open-label, randomized, parallel and standard
      chemoradiation-controlled study where eligible subjects will be randomized at 1:1 ratio to
      receive control treatment or study treatment. The primary objective of this trial is to
      evaluate the effect of add-on JP001 to standard chemoradiation in increasing overall survival
      (OS) on newly diagnosed glioblastoma (GBM) patients.
After enrollment, subjects' previous tumor block used for glioblastoma diagnosis that is
      consented to provide during the study period will be sent to a central laboratory for the
      assessment of MGMT status. Moreover, subjects will be randomized in either Control or Study
      arm at Visit 2. Subjects in Control arm will receive a standard chemoradiation. However,
      subjects in Study arm will receive a standard chemoradiation in combination with concurrent
      JP001 in whole study period. During the study, a sufficient amount of investigational
      products will be supplied to subjects in study groups until next scheduled visits. Subjects
      will self-administer investigational product orally with water at approximately the same time
      in each day. Subjects should fast for a minimum of 2 hours prior to any doses of JP001 and/or
      Temozolomide and then fast for another 1 hour after taking JP001 and/or Temozolomide. During
      and at the end of treatment, subjects will be evaluated for efficacy and safety parameters.
      Moreover, there will be a Follow-up visit for safety 4 weeks after the End-of-Treatment
      visit. If a subject is early withdrawn from the study, the End-of-Treatment visit should be
      arranged and all assessments assigned in this visit should be performed. The Safety Follow-up
      visit for early withdrawn subjects could be either clinic visit or telephone contact. If
      withdrawn subjects refuse to perform Follow-up visit, the Follow-up visit is allowed to
      cancel. For subjects who completed or discontinued study treatment, assessment of survival
      status will be performed every 8 weeks by telephone contact until death, study end (last
      subject last visit; the last subject needs to be followed at least 30 months), or study
      termination by Sponsor. Survival information will be recorded in the medical source and CRF.
      If subjects are lost to follow-up or refuse to receive the assessment of survival status, the
      investigator will record the last date subjects known to be alive in the medical source and
      case report form.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival time.
time frame: 120 weeks
description: All subjects will be followed until study end (the date of last subject last visit; the last subject need to be followed at least 30 months) or death, whichever comes first; OS defined as the time from the date of Randomization to the date of death or last follow-up.
measure: Progression-free survival time
time frame: 120 weeks
description: All subjects will be followed until study end or disease progression confirmed, whichever comes first; PFS defined as the time from the date of Randomization to the date of disease progression, death or last follow-up.
measure: OS rate at 1 year.
time frame: 1 year
description: OS defined as the time from the date of Randomization to the date of death or last follow-up.
measure: PFS rate at 1 year.
time frame: 1 year
description: PFS defined as the time from the date of Randomization to the date of disease progression, death or last follow-up.
measure: The time and rate of OS in different RPA class.
time frame: 120 weeks
measure: The time and rate of PFS in different RPA class.
time frame: 120 weeks
measure: Objective response rate.
time frame: 120 weeks
description: Defined as the proportion of subjects who were confirmed completed response or partial response determined by RANO criteria.
measure: Changes in score of EORTC QLQ-C30
time frame: 120 weeks
measure: Changes in score of EORTC QLQ-BN20.
time frame: 120 weeks
measure: Changes in grade of ECOG performance status.
time frame: 120 weeks
arm group label: Radiation,Temozolomide
arm group type: Active Comparator
description: CCRT Phase: Radiation(60 Gy in 2 Gy/fx) + daily Temozolomide (75 mg/m²/day for 6 weeks).
Rest Phase: Rest for 4 weeks.
Chemotherapy Phase: Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles.
Maintenance Phase: No maintenance treatment until disease progression confirmed.
arm group label: Radiation,Temozolomide,Siroquine(JP001)
arm group type: Experimental
description: CCRT Phase: Radiation(60 Gy in 2 Gy/fx) + daily Temozolomide (75 mg/m²/day for 6 weeks) + Daily JP001 (2 tablets once a day for 6 weeks).
Rest Phase: Daily JP001(2 tablets/day) for 4 weeks.
Chemotherapy Phase: Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles + Daily JP001(2 tablets once a day) for 24 weeks (4 weeks for each cycle).
Maintenance Phase: JP001(2 tablets once a day) until disease progression confirmed.
intervention type: Radiation
intervention name: CCRT
description: CCRT Phase: Radiation(60 Gy in 2 Gy/fx) + daily Temozolomide (75 mg/m²/day for 6 weeks).
arm group label: Radiation,Temozolomide
arm group label: Radiation,Temozolomide,Siroquine(JP001)
intervention type: Drug
intervention name: Temozolomide
description: Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles.
arm group label: Radiation,Temozolomide
arm group label: Radiation,Temozolomide,Siroquine(JP001)
other name: Chemotherapy
intervention type: Drug
intervention name: Siroquine
description: Chemotherapy Phase: Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles + Daily JP001(2 tablets once a day) for 24 weeks (4 weeks for each cycle).
Maintenance Phase: JP001(2 tablets once a day) until disease progression confirmed.
arm group label: Radiation,Temozolomide,Siroquine(JP001)
other name: JP001
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
last name: Kwan-Hwa Chi
phone: 886-2-28332211
phone ext: 2274
email: M006565@ms.skh.org.tw
last name: Susan Huang
phone: 886-2-28332211
phone ext: 2612
email: susan.huang@johnpro.com.tw
facility: 
status: Recruiting
investigator: 
facility: 
status: Not yet recruiting
investigator: 
country: Taiwan
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Temozolomide
sharing ipd: No