<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/NCT03823989</url>
  </required_header>
  <id_info>
    <org_study_id>LIPORAD-2018</org_study_id>
    <nct_id>NCT03823989</nct_id>
  </id_info>
  <brief_title>Intravenously Administered Liposomal PROMITIL in Combination With External Beam Radiotherapy in Cancer Patients</brief_title>
  <official_title>An Open-label, Phase 1b Study of Intravenously Administered Pegylated Liposomal Mitomycin C Lipid-based Prodrug (PROMITIL) in Combination With External Beam Radiotherapy in Patients With Advanced Cancer Requiring Palliative Radiotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lipomedix Pharmaceuticals Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lipomedix Pharmaceuticals 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 will be a multi-center, open-label, single-arm, prospective study, in which up to 18&#xD;
      adult patients requiring radiotherapy for metastatic disease or for an inoperable primary&#xD;
      tumor with no definitive curative treatment option, will undergo a combination treatment of&#xD;
      intravenously (IV) delivered PROMITIL and standard of care radiotherapy. The treatment&#xD;
      regimen will involve administration of two PROMITIL doses, delivered at a 21-day interval,&#xD;
      and a course of EBR (type of RT according to investigator's preference), initiated 1-3 days&#xD;
      after the first PROMITIL dose and completed within a 2-week period. EBR will consist of no&#xD;
      more than 10 fractions delivered within 2 weeks as conventionally fractionated RT, or SBRT.&#xD;
      Treatment safety will be assessed on a weekly basis throughout the two 21-day treatment&#xD;
      courses (42 days) and throughout the follow-up period (up to Day 127). AEs will only be&#xD;
      logged until 6 weeks after the last PROMITIL dose (up until Day 64). Disease status will be&#xD;
      reevaluated between days 43-50 of the study, and every 6 weeks thereafter (Days 85 and 127±7&#xD;
      days). In addition, following completion of the treatment schedule, all patients will be&#xD;
      followed up by phone every 12 weeks, until either death, disease progression (PD), withdrawn&#xD;
      consent or trial cut-off date, i.e., for up to 2 years after patient accrual to study,&#xD;
      (whichever occurs first). The following anticancer agents will NOT be allowed during the&#xD;
      screening period, 6-week treatment period and until first disease reevaluation: cytotoxic&#xD;
      agents, non-cytotoxic myelosuppressive agents (CDK 4/6 inibitiors, PARP inhibitors, m-TORS&#xD;
      inhibitors and tyrosine kinase-inhibitors). Treatment with hormonal agents, monoclonal&#xD;
      antibodies (anti-EGFr, anti-Her2, anti-VEGF and VEGFr, anti-PD1, anti-PDL1) and&#xD;
      bisphosphonates can be continued during the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As combination with radiotherapy is expected to provide an additive or synergistic effect,&#xD;
      the current dose-escalation study will begin with a dose of 1.25 mg/kg, to be followed by an&#xD;
      increase (1.5 mg/kg) in Cohort 2 and a further increase 1.8 mg/kg in Cohort 3 in the absence&#xD;
      of DLTs after two treatment cycles, with an interluding 10-fraction course of radiotherapy.&#xD;
&#xD;
      PROMITIL will be intravenously delivered on Day 1 of each of the two 21-day cycles.&#xD;
&#xD;
      Cohort 1: The first 6 patients recruited to the study will receive 1.25 mg/kg PROMITIL.&#xD;
&#xD;
      Cohort 2: If no dose-limiting toxicities (DLTs) are recorded by day 43 of the study, the&#xD;
      second cohort of 6 patients will begin treatment at a dose level of 1.5 mg/kg PROMITIL.&#xD;
      However, if 1 DLT is recorded, the second cohort of 6 patients will receive the same dose of&#xD;
      1.25 mg/kg PROMITIL. If 2 DLTs are recorded in Cohort 1, the second cohort of 6 patients will&#xD;
      receive 1.0 mg/kg PROMITIL.&#xD;
&#xD;
      Cohort 3: If no dose-limiting toxicities (DLTs) are recorded by day 43 of the study of the&#xD;
      first 3 patients of Cohort 2, a third cohort will enroll 6 patients to receive treatment at a&#xD;
      dose level of 1.8 mg/kg PROMITIL. If none or 1 DLT is recorded, the dose of 1.8 mg/kg will be&#xD;
      cleared as recommended dose for phase 2. If 2 DLT are recorded, the study will be terminated&#xD;
      as soon as the 2nd DLT is recorded, and the prior dose level of 1.5 mg/kg will be cleared as&#xD;
      recommended dose for phase 2&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 3, 2019</start_date>
  <completion_date type="Actual">December 30, 2021</completion_date>
  <primary_completion_date type="Actual">October 31, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>dose-escalation study will begin with a dose of 1.25 mg/kg, to be followed by an increase to 1.5 mg/kg PROMITIL and a further increase 1.8 mg/kg in the absence of DLTs after two treatment cycles, with an interluding 10-fraction course of radiotherapy. Upon completion of two treatment cycles, with ≤1 incident of DLTs in Cohort 2, a third confirmatory cohort (n=6) will be recruited and will be treated with the same dose as that administered to Cohort 2</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose limiting toxicity (DLT) of Promitil in combination with external beam radiotherapy (EBR)</measure>
    <time_frame>6 weeks</time_frame>
    <description>Report of Dose limiting toxicity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>6 weeks</time_frame>
    <description>Incidence all Adverse events of Promitil in combination with external beam radiotherapy (EBR)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To evaluate the response rate to PROMITIL in combination with external beam radiotherapy (EBR)</measure>
    <time_frame>7 weeks</time_frame>
    <description>Local disease control in irradiated tumor areas at first reevaluation (Day 43-50), defined as rate of complete response [CR], partial response [PR] and stable disease [SD], as per RECIST 1.1 criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of response of the irradiated tumor site</measure>
    <time_frame>18 weeks</time_frame>
    <description>Duration of response (in weeks) of the irradiated tumor site, from first evidence of response (Stable disease or better) to confirmed Progression disease (as per RECIST 1.1 criteria)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>18 weeks</time_frame>
    <description>Progression-free survival (PFS) (in weeks), from day of first dose of PROMITIL until confirmed Progression disease (as per RECIST 1.1 criteria)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>34 weeks</time_frame>
    <description>Overall survival (in weeks), from day of first dose of PROMITIL to death of any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma MLP level after Promitil infusion</measure>
    <time_frame>6 weeks (2 cycles of treatment)</time_frame>
    <description>Plasma MLP levels before and after (1 h and 24 h) each PROMITIL dose</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Cancer</condition>
  <condition>Solid Tumor</condition>
  <condition>Metastatic Disease</condition>
  <arm_group>
    <arm_group_label>Promitil 1.25 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two treatment cycles, intravenous infusion of Promitil at a dosage of 1.25 mg/kg delivered at 21 days interval and a 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Promitil 1.5 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two treatment cycles, intravenous infusion of Promitil at a dosage of 1.5 mg/kg delivered at 21 days interval and a 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Promitil 1.8 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>two treatment cycles, intravenous infusion of Promitil at a dosage of 1.8 mg/kg delivered at 21 days interval (confirmatory cohort) and a 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Promitil</intervention_name>
    <description>The first 6 patients recruited to the study will receive 1.25 mg/kg PROMITIL. If no dose-limiting toxicities (DLTs) are recorded by day 43 of the study, the second cohort of 6 patients will begin treatment at a dose level of 1.5 mg/kg PROMITIL. Upon completion of two treatment cycles, with ≤1 incident of DLTs in Cohort 2, a third cohort (n=6) will be recruited and will be treated with a dose level of 1.8 mg/kg.</description>
    <arm_group_label>Promitil 1.25 mg/kg</arm_group_label>
    <arm_group_label>Promitil 1.5 mg/kg</arm_group_label>
    <arm_group_label>Promitil 1.8 mg/kg</arm_group_label>
    <other_name>Pegylated Liposomal Mitomycin-C Lipid-based Prodrug</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>EBR</intervention_name>
    <description>A 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.</description>
    <arm_group_label>Promitil 1.25 mg/kg</arm_group_label>
    <arm_group_label>Promitil 1.5 mg/kg</arm_group_label>
    <arm_group_label>Promitil 1.8 mg/kg</arm_group_label>
    <other_name>external beam radiotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with histologically or cytologically confirmed recurrent and/or metastatic,&#xD;
             cancer, with at least one measurable lesion (≤10 cm diameter) on file, and with no&#xD;
             definitive curative treatment option.&#xD;
&#xD;
          2. A ≥21-day treatment-free interval from last chemotherapeutic treatment (including&#xD;
             cytotoxic or non-cytotoxic myelosuppressive agents), and ≥14-day treatment-free&#xD;
             interval from biological therapies consisting of CDK 4/6 inibitiors, PARP inhibitors,&#xD;
             m-TOR inhibitors Hormonal therapies including LH-RH analogs or anagonists, tamoxifen,&#xD;
             aromatase inhibitors, bicalutamide, aboraterone, corticosteroids, or enzalutamide may&#xD;
             be continued uninterruptedly.&#xD;
&#xD;
          3. No prior intravenous treatment with mitomycin-C either alone or in combination&#xD;
&#xD;
          4. No prior extensive radiotherapy (e.g., whole pelvis, or greater than 50% of neuroaxis,&#xD;
             whole abdomen, whole body or half-body) or bone marrow transplantation with high dose&#xD;
             chemotherapy.&#xD;
&#xD;
          5. No prior radiotherapy to the same anatomic site aimed for radiotherapy.&#xD;
&#xD;
          6. Age ≥18years&#xD;
&#xD;
          7. BMI: 18-36&#xD;
&#xD;
          8. ECOG Performance Status ≤ 2&#xD;
&#xD;
          9. Estimated life expectancy of at least 3 months&#xD;
&#xD;
         10. Adequate bone marrow function (an absolute neutrophil count ≥1500/mm3, hemoglobin ≥9.5&#xD;
             g/dl, and a platelet count ≥100,000/mm3);&#xD;
&#xD;
         11. Adequate liver function (serum bilirubin ≤2.0 mg/100 ml; alanine aminotransferase ≤3×&#xD;
             ULN, albumin ≥34g/L)&#xD;
&#xD;
         12. Adequate renal function (serum creatinine ≤1.5 mg/100 ml or creatinine clearance ≥40&#xD;
             ml/min/1.73m2)&#xD;
&#xD;
         13. Women of child-bearing potential practicing an acceptable method of birth control.&#xD;
&#xD;
         14. Understanding of study procedures and willingness to comply for the entire length of&#xD;
             the study and to provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known hypersensitivity to the study drug or to any of its components&#xD;
&#xD;
          2. Prior intravenous treatment with mitomycin C&#xD;
&#xD;
          3. Patients requiring whole-brain irradiation&#xD;
&#xD;
          4. Patients requiring re-irradiation of the same tumor/anatomical site.&#xD;
&#xD;
          5. CHF (NYHA = Class IV)&#xD;
&#xD;
          6. Severe COPD or Stage ≥3 severe emphysema with FEV1 between 30 and 50 percent of normal&#xD;
&#xD;
          7. Chronic liver disease or cirrhosis with Child-Pugh Class C score&#xD;
&#xD;
          8. Any other severe concurrent disease which in the judgment of the investigator would&#xD;
             make the subject unsuitable for entry into this study&#xD;
&#xD;
          9. History of human immunodeficiency virus (HIV) infection&#xD;
&#xD;
         10. History of chronic active hepatitis including subjects who are carriers of hepatitis B&#xD;
             virus (HBV) or hepatitis C virus (HCV), unless adequately treated and shown to be&#xD;
             serum virus-free.&#xD;
&#xD;
         11. Presence of uncontrolled infection.&#xD;
&#xD;
         12. Evidence of active bleeding or bleeding diathesis&#xD;
&#xD;
         13. Pregnant or lactating&#xD;
&#xD;
         14. Treatment with other investigational drugs within &lt;21 days of start of day 1 of study&#xD;
             drug.&#xD;
&#xD;
         15. Uncontrolled ascites (defined as 2 or more palliative taps in the last 21 days before&#xD;
             screening).&#xD;
&#xD;
             -&#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>Adi Levy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hadassah Medical Organization</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Eli Sapir, MD</last_name>
    <role>Study Director</role>
    <affiliation>Assuta Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Assuta Ashdod</name>
      <address>
        <city>Ashdod</city>
        <zip>7747629</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Assuta Medical Center</name>
      <address>
        <city>Tel Aviv</city>
        <zip>6971028</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <reference>
    <citation>Tian X, Warner SB, Wagner KT, Caster JM, Zhang T, Ohana P, Gabizon AA, Wang AZ. Preclinical Evaluation of Promitil, a Radiation-Responsive Liposomal Formulation of Mitomycin C Prodrug, in Chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2016 Nov 1;96(3):547-55. doi: 10.1016/j.ijrobp.2016.06.2457. Epub 2016 Jul 1.</citation>
    <PMID>27681751</PMID>
  </reference>
  <reference>
    <citation>Tahover E, Bar-Shalom R, Sapir E, Pfeffer R, Nemirovsky I, Turner Y, Gips M, Ohana P, Corn BW, Wang AZ, Gabizon AA. Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience. Front Oncol. 2018 Nov 26;8:544. doi: 10.3389/fonc.2018.00544. eCollection 2018.</citation>
    <PMID>30534533</PMID>
  </reference>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <last_update_submitted>January 5, 2022</last_update_submitted>
  <last_update_submitted_qc>January 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2022</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>Neoplasm Metastasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mitomycins</mesh_term>
    <mesh_term>Mitomycin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The PI and the sponsor have still to discuss what will be the plan to share IPD</ipd_description>
  </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/NCT03823989
org study id: LIPORAD-2018
nct id: NCT03823989
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This will be a multi-center, open-label, single-arm, prospective study, in which up to 18
      adult patients requiring radiotherapy for metastatic disease or for an inoperable primary
      tumor with no definitive curative treatment option, will undergo a combination treatment of
      intravenously (IV) delivered PROMITIL and standard of care radiotherapy. The treatment
      regimen will involve administration of two PROMITIL doses, delivered at a 21-day interval,
      and a course of EBR (type of RT according to investigator's preference), initiated 1-3 days
      after the first PROMITIL dose and completed within a 2-week period. EBR will consist of no
      more than 10 fractions delivered within 2 weeks as conventionally fractionated RT, or SBRT.
      Treatment safety will be assessed on a weekly basis throughout the two 21-day treatment
      courses (42 days) and throughout the follow-up period (up to Day 127). AEs will only be
      logged until 6 weeks after the last PROMITIL dose (up until Day 64). Disease status will be
      reevaluated between days 43-50 of the study, and every 6 weeks thereafter (Days 85 and 127±7
      days). In addition, following completion of the treatment schedule, all patients will be
      followed up by phone every 12 weeks, until either death, disease progression (PD), withdrawn
      consent or trial cut-off date, i.e., for up to 2 years after patient accrual to study,
      (whichever occurs first). The following anticancer agents will NOT be allowed during the
      screening period, 6-week treatment period and until first disease reevaluation: cytotoxic
      agents, non-cytotoxic myelosuppressive agents (CDK 4/6 inibitiors, PARP inhibitors, m-TORS
      inhibitors and tyrosine kinase-inhibitors). Treatment with hormonal agents, monoclonal
      antibodies (anti-EGFr, anti-Her2, anti-VEGF and VEGFr, anti-PD1, anti-PDL1) and
      bisphosphonates can be continued during the study.
As combination with radiotherapy is expected to provide an additive or synergistic effect,
      the current dose-escalation study will begin with a dose of 1.25 mg/kg, to be followed by an
      increase (1.5 mg/kg) in Cohort 2 and a further increase 1.8 mg/kg in Cohort 3 in the absence
      of DLTs after two treatment cycles, with an interluding 10-fraction course of radiotherapy.

      PROMITIL will be intravenously delivered on Day 1 of each of the two 21-day cycles.

      Cohort 1: The first 6 patients recruited to the study will receive 1.25 mg/kg PROMITIL.

      Cohort 2: If no dose-limiting toxicities (DLTs) are recorded by day 43 of the study, the
      second cohort of 6 patients will begin treatment at a dose level of 1.5 mg/kg PROMITIL.
      However, if 1 DLT is recorded, the second cohort of 6 patients will receive the same dose of
      1.25 mg/kg PROMITIL. If 2 DLTs are recorded in Cohort 1, the second cohort of 6 patients will
      receive 1.0 mg/kg PROMITIL.

      Cohort 3: If no dose-limiting toxicities (DLTs) are recorded by day 43 of the study of the
      first 3 patients of Cohort 2, a third cohort will enroll 6 patients to receive treatment at a
      dose level of 1.8 mg/kg PROMITIL. If none or 1 DLT is recorded, the dose of 1.8 mg/kg will be
      cleared as recommended dose for phase 2. If 2 DLT are recorded, the study will be terminated
      as soon as the 2nd DLT is recorded, and the prior dose level of 1.5 mg/kg will be cleared as
      recommended dose for phase 2
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: dose-escalation study will begin with a dose of 1.25 mg/kg, to be followed by an increase to 1.5 mg/kg PROMITIL and a further increase 1.8 mg/kg in the absence of DLTs after two treatment cycles, with an interluding 10-fraction course of radiotherapy. Upon completion of two treatment cycles, with ≤1 incident of DLTs in Cohort 2, a third confirmatory cohort (n=6) will be recruited and will be treated with the same dose as that administered to Cohort 2
primary purpose: Treatment
masking: None (Open Label)
measure: Dose limiting toxicity (DLT) of Promitil in combination with external beam radiotherapy (EBR)
time frame: 6 weeks
description: Report of Dose limiting toxicity
measure: Incidence of Treatment-Emergent Adverse Events
time frame: 6 weeks
description: Incidence all Adverse events of Promitil in combination with external beam radiotherapy (EBR)
measure: To evaluate the response rate to PROMITIL in combination with external beam radiotherapy (EBR)
time frame: 7 weeks
description: Local disease control in irradiated tumor areas at first reevaluation (Day 43-50), defined as rate of complete response [CR], partial response [PR] and stable disease [SD], as per RECIST 1.1 criteria
measure: Duration of response of the irradiated tumor site
time frame: 18 weeks
description: Duration of response (in weeks) of the irradiated tumor site, from first evidence of response (Stable disease or better) to confirmed Progression disease (as per RECIST 1.1 criteria)
measure: Progression-free survival (PFS)
time frame: 18 weeks
description: Progression-free survival (PFS) (in weeks), from day of first dose of PROMITIL until confirmed Progression disease (as per RECIST 1.1 criteria)
measure: Overall survival
time frame: 34 weeks
description: Overall survival (in weeks), from day of first dose of PROMITIL to death of any cause
measure: Plasma MLP level after Promitil infusion
time frame: 6 weeks (2 cycles of treatment)
description: Plasma MLP levels before and after (1 h and 24 h) each PROMITIL dose
arm group label: Promitil 1.25 mg/kg
arm group type: Experimental
description: Two treatment cycles, intravenous infusion of Promitil at a dosage of 1.25 mg/kg delivered at 21 days interval and a 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.
arm group label: Promitil 1.5 mg/kg
arm group type: Experimental
description: Two treatment cycles, intravenous infusion of Promitil at a dosage of 1.5 mg/kg delivered at 21 days interval and a 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.
arm group label: Promitil 1.8 mg/kg
arm group type: Experimental
description: two treatment cycles, intravenous infusion of Promitil at a dosage of 1.8 mg/kg delivered at 21 days interval (confirmatory cohort) and a 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.
intervention type: Drug
intervention name: Promitil
description: The first 6 patients recruited to the study will receive 1.25 mg/kg PROMITIL. If no dose-limiting toxicities (DLTs) are recorded by day 43 of the study, the second cohort of 6 patients will begin treatment at a dose level of 1.5 mg/kg PROMITIL. Upon completion of two treatment cycles, with ≤1 incident of DLTs in Cohort 2, a third cohort (n=6) will be recruited and will be treated with a dose level of 1.8 mg/kg.
arm group label: Promitil 1.25 mg/kg
arm group label: Promitil 1.5 mg/kg
arm group label: Promitil 1.8 mg/kg
other name: Pegylated Liposomal Mitomycin-C Lipid-based Prodrug
intervention type: Radiation
intervention name: EBR
description: A 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.
arm group label: Promitil 1.25 mg/kg
arm group label: Promitil 1.5 mg/kg
arm group label: Promitil 1.8 mg/kg
other name: external beam radiotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Adi Levy, MD
role: Principal Investigator
affiliation: Hadassah Medical Organization
last name: Eli Sapir, MD
role: Study Director
affiliation: Assuta Medical Center
facility: 
facility: 
facility: 
country: Israel
citation: Tian X, Warner SB, Wagner KT, Caster JM, Zhang T, Ohana P, Gabizon AA, Wang AZ. Preclinical Evaluation of Promitil, a Radiation-Responsive Liposomal Formulation of Mitomycin C Prodrug, in Chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2016 Nov 1;96(3):547-55. doi: 10.1016/j.ijrobp.2016.06.2457. Epub 2016 Jul 1.
PMID: 27681751
citation: Tahover E, Bar-Shalom R, Sapir E, Pfeffer R, Nemirovsky I, Turner Y, Gips M, Ohana P, Corn BW, Wang AZ, Gabizon AA. Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience. Front Oncol. 2018 Nov 26;8:544. doi: 10.3389/fonc.2018.00544. eCollection 2018.
PMID: 30534533
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Mitomycins
mesh term: Mitomycin
sharing ipd: No
ipd description: The PI and the sponsor have still to discuss what will be the plan to share IPD