<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/NCT01705002</url>
  </required_header>
  <id_info>
    <org_study_id>PROMITIL-01</org_study_id>
    <nct_id>NCT01705002</nct_id>
  </id_info>
  <brief_title>Intravenously Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PROMITIL) in Cancer Patients With Solid Tumors.</brief_title>
  <official_title>A Phase I, Dose-Escalating, Safety Study of an Intravenously Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PL-MLP, PROMITIL) in Cancer Patients With Solid Tumors.</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase I, multi-center, Dose-Escalating, Safety Study of an Intravenously&#xD;
      Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PL-MLP, PROMITIL) in Cancer&#xD;
      Patients with Solid Tumors. The study comprised of:&#xD;
&#xD;
      Escalated cohorts A-H: 27 male or female participants, ages 18-80, BMI 18-36 diagnosed with&#xD;
      inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have&#xD;
      failed to respond to standard therapy or for whom no standard therapy is available. Eligible&#xD;
      subjects will be assigned, successively in order of accrual, to one of eight cohorts, to&#xD;
      receive escalating doses of intravenously infused PROMITIL. PROMITIL will be administered as&#xD;
      an intravenous infusion. Dose escalation will only proceed in the absence of dose-limiting&#xD;
      toxicity (DLT). For this purpose, each cohort will only begin its first cycle of PROMITIL&#xD;
      when the cohort preceding it has successfully completed its first 4-week cycle without any&#xD;
      signs of DLT.&#xD;
&#xD;
      Expanded cohort: 17 adult patients with metastatic CRC. The purpose of this expanded cohort&#xD;
      is to further evaluate the safety of Promitil and to search for signs of antitumor activity&#xD;
      of Promitil in this specific patient population.&#xD;
&#xD;
      Combination Cohort (Promitil concomitantly with Capecitabine): 23 adult patients with&#xD;
      metastatic CRC.&#xD;
&#xD;
      Triple combination Cohort: 13 additional subjects with metastatic CRC, received combination&#xD;
      of Promitil concomitantly with Bevacizumab (5 mg/kg) on day 1 of a 28 day cycle and&#xD;
      Capecitabine on days 1-14 of a 28 day cycle.&#xD;
&#xD;
      3 weekly cohort- 9 subjects with metastatic CRC will receive Promitil and Bevacizumab (7.5&#xD;
      mg/kg) on day 1 of a 21 day cycle.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For all cohorts, PROMITIL will be administered as an intravenous infusion at an initial rate&#xD;
      of 0.25mg/min followed by gradual increase to a maximal rate of 2mg/min until completion of&#xD;
      dosing, if absence of infusion reactions is established and in line with most updated version&#xD;
      of IFU available for this study.&#xD;
&#xD;
      For each subject, subsequent dosing will take place 28 days after the previous treatment,&#xD;
      provided they are deemed fit to be dosed again.&#xD;
&#xD;
      Patients will return to the study center on days 8, 15, 22 of cycle 1, and on day 15 of&#xD;
      cycles 2 and 3, for monitoring assessments.&#xD;
&#xD;
      All patients will be followed-up for survival and post-Promitil treatment. Patients who did&#xD;
      not received 3 cycles of PROMITIL will be followed up only until PD.&#xD;
&#xD;
      For the 3 weekly cohort Promitil will be administered at 3 week interval together with&#xD;
      Bevacizumab (7.5 mg/kg). Patients will return to the study center on days 8 and 15 of cycle&#xD;
      1, and on day 15 of cycles 2 and 3, for monitoring assessments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">November 2017</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximal Tolerated Dose (MTD) of PROMITIL</measure>
    <time_frame>First cycle of treatment (4 weeks)</time_frame>
    <description>Only DLTs occurring during the first cycle of treatment for each participant will determine MTD endpoint</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose Limiting Toxicity (DLT) of PROMITIL</measure>
    <time_frame>First cycle of treatment (4 weeks)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) profile of PROMITIL</measure>
    <time_frame>3 cycles of treatment (12 weeks)</time_frame>
    <description>PK assessments will monitor plasma levels of MLP and metabolite (MMC), as well as PK parameters (Cmax, AUC0-t, AUC 0-∞, MRT, t½ , Kel, Cl, VD).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anti-tumor responses to the delivered PROMITIL regimens</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity profile of PROMITIL</measure>
    <time_frame>3 cycles of treatment (12 weeks)</time_frame>
  </secondary_outcome>
  <number_of_arms>12</number_of_arms>
  <enrollment type="Actual">88</enrollment>
  <condition>Cancer</condition>
  <condition>Solid Tumor</condition>
  <condition>Metastatic Colorectal Cancer (mCRC)</condition>
  <arm_group>
    <arm_group_label>Cohort A: Promitil 0.5 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Three treatment cycles, intravenous infusion of Promitil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B: Promitil 1.0 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Three treatment cycles, intravenous infusion of Promitil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C: Promitil 1.5 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Three treatment cycles, intravenous infusion of Promitil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort D: Promitil 2.0 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Three treatment cycles, intravenous infusion of Promitil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort E: Promitil 2.5 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Three treatment cycles, intravenous infusion of Promitil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort F: Promitil 3.0 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Three treatment cycles, intravenous infusion of Promitil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort G: Promitil 3.5 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Three treatment cycles, intravenous infusion of Promitil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort H: Promitil 4.0 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Three treatment cycles, intravenous infusion of Promitil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Expanded Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with the selected RP2D of PROMITIL (3 mg/kg) intravenously administered on their first cycle and reduced dose of 2 mg/kg from cycle 2 and onwards.&#xD;
Only for mCRC patients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combination Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with one cycle of 2.5mg/kg Promitil day 1 together with Capecitabine 1,000 mg bid po days 1-21 followed by two cycles of 2.0 mg/kg Promitil day 1 together with Capecitabine 1,000 mg bid po days 1-21, at four-week intervals.&#xD;
Only for mCRC patients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Triple combination Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with one cycle of 2mg/kg Promitil I.v and 5 mg/kg Bevacizumab i.v on day 1 together with Capecitabine 1,000 mg bid p.o days 1-14 at four-week intervals.&#xD;
Only for mCRC patients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3 Weekly Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with one cycle of 2mg/kg Promitil I.v and 7.5 mg/kg Bevacizumab i.v on day 1 together at three-week intervals.&#xD;
Only for mCRC patients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Promitil</intervention_name>
    <description>2 mg/kg dose IV</description>
    <arm_group_label>3 Weekly Cohort</arm_group_label>
    <arm_group_label>Cohort A: Promitil 0.5 mg/kg</arm_group_label>
    <arm_group_label>Cohort B: Promitil 1.0 mg/kg</arm_group_label>
    <arm_group_label>Cohort C: Promitil 1.5 mg/kg</arm_group_label>
    <arm_group_label>Cohort D: Promitil 2.0 mg/kg</arm_group_label>
    <arm_group_label>Cohort E: Promitil 2.5 mg/kg</arm_group_label>
    <arm_group_label>Cohort F: Promitil 3.0 mg/kg</arm_group_label>
    <arm_group_label>Cohort G: Promitil 3.5 mg/kg</arm_group_label>
    <arm_group_label>Cohort H: Promitil 4.0 mg/kg</arm_group_label>
    <arm_group_label>Combination Cohort</arm_group_label>
    <arm_group_label>Expanded Cohort</arm_group_label>
    <arm_group_label>Triple combination Cohort</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>1000 mg dose BID PO for days 1-21 for Combination Cohort and on day 1-14 on Triple combination Cohort</description>
    <arm_group_label>Combination Cohort</arm_group_label>
    <arm_group_label>Triple combination Cohort</arm_group_label>
    <other_name>Xeloda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>for Triple combination cohort an IV dose of 5 mg/kg on day 1 at 4 week interval. For the 3 weekly cohort an IV dose of 7.5 mg/kg at 3 week interval.</description>
    <arm_group_label>3 Weekly Cohort</arm_group_label>
    <arm_group_label>Triple combination Cohort</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients diagnosed with inoperable, recurrent or metastatic malignant solid tumors,&#xD;
             deemed incurable, and who have either:&#xD;
&#xD;
               -  Failed to respond to standard therapy or&#xD;
&#xD;
               -  For whom no standard therapy is available or&#xD;
&#xD;
               -  Refuse to receive standard therapies&#xD;
&#xD;
          2. Histologically or cytologically confirmed diagnosis of solid tumor on file.&#xD;
&#xD;
          3. Age 18-80 years&#xD;
&#xD;
          4. BMI: 18-36&#xD;
&#xD;
          5. ECOG Performance Status ≤ 2&#xD;
&#xD;
          6. Estimated life expectancy of at least 3 months&#xD;
&#xD;
          7. Adequate bone marrow function (an absolute neutrophil count ≥1500/mm3, hemoglobin ≥9.5&#xD;
             g/dl, HgbA1C≤7%, and a platelet count ≥100,000/mm3(&#xD;
&#xD;
          8. Adequate liver function (serum bilirubin ≤2.0 mg/100 ml; alanine aminotransferase ≤2×&#xD;
             ULN)&#xD;
&#xD;
          9. Adequate renal function (serum creatinine ≤1.5 mg/100 ml or creatinine clearance ≥45&#xD;
             ml/min/1.73m2)&#xD;
&#xD;
         10. No prior intravenous treatment with Mitomycin-C either alone or in combination&#xD;
&#xD;
         11. No other myelosuppressive treatment within 4 weeks before start of the study drug.&#xD;
&#xD;
         12. No other anti-cancer treatment within 2 weeks before start of the study drug&#xD;
&#xD;
         13. No prior extensive radiotherapy (e.g., whole pelvis total neuroaxis or greater than&#xD;
             50% of neuroaxis, whole abdomen, whole body or half-body) or bone marrow&#xD;
             transplantation with high dose chemotherapy and/or total body irradiation.&#xD;
             Re-irradiation of a field in abdomen/pelvis will be considered as extensive&#xD;
             radiotherapy, excluding such patients from the study.&#xD;
&#xD;
         14. Women of child bearing potential practicing an acceptable method of birth control.&#xD;
&#xD;
         15. Understanding of study procedures and willingness to comply for the entire length of&#xD;
             the study and to give written informed consent.&#xD;
&#xD;
         16. Additional criteria only for the Expanded Cohort and both Combination cohorts:&#xD;
             Patients with histologically or cytologically confirmed recurrent and/or metastatic&#xD;
             measurable or nonmeasurable CRC, with tissue or cytological diagnosis of cancer on&#xD;
             file.&#xD;
&#xD;
         17. Additional criteria only for the Expanded Cohort and both Combination cohort: Patients&#xD;
             who demonstrated either progression or intolerance when treated with irinotecan and&#xD;
             fluopyrimidine-based chemotherapy, and, in the case of K-ras wild type tumors,&#xD;
             anti-EGFR antibodies (Cetuximab, Panitumumab). Prior treatment with oxaliplatin or&#xD;
             bevacizumab is allowed but not required.&#xD;
&#xD;
         18. Additional criteria only for the Expanded Cohort and both Combination cohorts: A ≥28&#xD;
             day treatment-free interval between last chemotherapeutic treatment and first&#xD;
             treatment with Promitil, with the exception of Capecitabine and biological therapies,&#xD;
             where 14-day treatment-free intervals suffice. this is also relevant for patients in&#xD;
             the Combination Cohort that are currently taking Capecitabine prior to enter the&#xD;
             study).&#xD;
&#xD;
         19. Additional criteria for the Triple Combination Cohort with bevacizumab only: Prior&#xD;
             exposure to oxaliplatin should have terminated at least 6 months before start of&#xD;
             PROMITIL, whether given as adjuvant therapy or as therapy for metastatic disease.&#xD;
&#xD;
         20. Additional criteria for the triple Combination Cohort with bevacizumab only: A ≥ 28&#xD;
             day treatment-free interval from last bevacizumab treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known hypersensitivity to the study drug or to any of its components&#xD;
&#xD;
          2. CHF (NYHA = Class IV) or LVEF≤40%&#xD;
&#xD;
          3. COPD &gt; Stage 3 (FEV1&lt;50%, FEV1/FVC&lt;70%);&#xD;
&#xD;
          4. Cirrhosis (Child-Pugh Class C score);&#xD;
&#xD;
          5. Serum Albumin level &lt; 3 g/dl&#xD;
&#xD;
          6. Any other severe concurrent disease which in the judgment of the investigator would&#xD;
             make the subject inappropriate for entry into this study&#xD;
&#xD;
          7. History of human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          8. History of chronic active hepatitis including subjects who are carriers of hepatitis B&#xD;
             virus (HBV) or hepatitis C virus (HCV).&#xD;
&#xD;
          9. Presence of uncontrolled infection.&#xD;
&#xD;
         10. Evidence of active bleeding or bleeding diathesis&#xD;
&#xD;
         11. Brain metastases in symptomatic patients requiring ≥4 mg dexamethasone/day. However,&#xD;
             patients with treated brain metastases by surgery or radiation who are stable and&#xD;
             symptom-free (&lt;4 mg dexamethasone/day) for a minimum period of 4 weeks post-treatment&#xD;
             are eligible.&#xD;
&#xD;
         12. Pregnant or lactating&#xD;
&#xD;
         13. Treatment with other investigational drugs within 14 days of start of the study drug&#xD;
             for non-myelosuppressive agents, and within 28 days of start of the study drug for&#xD;
             myelosuppressive agents.&#xD;
&#xD;
         14. Additional criteria for the Combination cohorts: Uncontrolled ascites (defined as 2 or&#xD;
             more palliative taps in the last 30 days before screening).&#xD;
&#xD;
         15. Additional criteria for the Combination cohorts with bevacizumab only: uncontrolled&#xD;
             clinically significant cardiac disease, hypertension, arrhythmias, or angina pectoris;&#xD;
             acute myocardial infarction or cerebrovascular accident within 12 months of initiation&#xD;
             of PROMITIL treatment.&#xD;
&#xD;
         16. Additional criteria for the Combination cohorts with bevacizumab only: Any&#xD;
             contraindication for treatment with Bevacizumab (e.g active bleeding, recent extensive&#xD;
             surgery).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Rambam Health Care Campus</name>
      <address>
        <city>Haifa</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shaare Zedek Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chaim Sheba Medical center</name>
      <address>
        <city>Ramat Gan</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tel-Aviv Sourasky Medical Center</name>
      <address>
        <city>Tel-Aviv</city>
        <zip>64239</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <last_update_submitted>July 9, 2018</last_update_submitted>
  <last_update_submitted_qc>July 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>phase 1</keyword>
  <keyword>dose escalating</keyword>
  <keyword>prodrug</keyword>
  <keyword>mitomycin C</keyword>
  <keyword>Capecitabine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01705002
org study id: PROMITIL-01
nct id: NCT01705002
lead sponsor: 
has dmc: Yes
This is a Phase I, multi-center, Dose-Escalating, Safety Study of an Intravenously
      Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PL-MLP, PROMITIL) in Cancer
      Patients with Solid Tumors. The study comprised of:

      Escalated cohorts A-H: 27 male or female participants, ages 18-80, BMI 18-36 diagnosed with
      inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have
      failed to respond to standard therapy or for whom no standard therapy is available. Eligible
      subjects will be assigned, successively in order of accrual, to one of eight cohorts, to
      receive escalating doses of intravenously infused PROMITIL. PROMITIL will be administered as
      an intravenous infusion. Dose escalation will only proceed in the absence of dose-limiting
      toxicity (DLT). For this purpose, each cohort will only begin its first cycle of PROMITIL
      when the cohort preceding it has successfully completed its first 4-week cycle without any
      signs of DLT.

      Expanded cohort: 17 adult patients with metastatic CRC. The purpose of this expanded cohort
      is to further evaluate the safety of Promitil and to search for signs of antitumor activity
      of Promitil in this specific patient population.

      Combination Cohort (Promitil concomitantly with Capecitabine): 23 adult patients with
      metastatic CRC.

      Triple combination Cohort: 13 additional subjects with metastatic CRC, received combination
      of Promitil concomitantly with Bevacizumab (5 mg/kg) on day 1 of a 28 day cycle and
      Capecitabine on days 1-14 of a 28 day cycle.

      3 weekly cohort- 9 subjects with metastatic CRC will receive Promitil and Bevacizumab (7.5
      mg/kg) on day 1 of a 21 day cycle.
For all cohorts, PROMITIL will be administered as an intravenous infusion at an initial rate
      of 0.25mg/min followed by gradual increase to a maximal rate of 2mg/min until completion of
      dosing, if absence of infusion reactions is established and in line with most updated version
      of IFU available for this study.

      For each subject, subsequent dosing will take place 28 days after the previous treatment,
      provided they are deemed fit to be dosed again.

      Patients will return to the study center on days 8, 15, 22 of cycle 1, and on day 15 of
      cycles 2 and 3, for monitoring assessments.

      All patients will be followed-up for survival and post-Promitil treatment. Patients who did
      not received 3 cycles of PROMITIL will be followed up only until PD.

      For the 3 weekly cohort Promitil will be administered at 3 week interval together with
      Bevacizumab (7.5 mg/kg). Patients will return to the study center on days 8 and 15 of cycle
      1, and on day 15 of cycles 2 and 3, for monitoring assessments.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximal Tolerated Dose (MTD) of PROMITIL
time frame: First cycle of treatment (4 weeks)
description: Only DLTs occurring during the first cycle of treatment for each participant will determine MTD endpoint
measure: Dose Limiting Toxicity (DLT) of PROMITIL
time frame: First cycle of treatment (4 weeks)
measure: Pharmacokinetic (PK) profile of PROMITIL
time frame: 3 cycles of treatment (12 weeks)
description: PK assessments will monitor plasma levels of MLP and metabolite (MMC), as well as PK parameters (Cmax, AUC0-t, AUC 0-∞, MRT, t½ , Kel, Cl, VD).
measure: Anti-tumor responses to the delivered PROMITIL regimens
time frame: 12 months
measure: Toxicity profile of PROMITIL
time frame: 3 cycles of treatment (12 weeks)
arm group label: Cohort A: Promitil 0.5 mg/kg
arm group type: Experimental
description: Three treatment cycles, intravenous infusion of Promitil
arm group label: Cohort B: Promitil 1.0 mg/kg
arm group type: Experimental
description: Three treatment cycles, intravenous infusion of Promitil
arm group label: Cohort C: Promitil 1.5 mg/kg
arm group type: Experimental
description: Three treatment cycles, intravenous infusion of Promitil
arm group label: Cohort D: Promitil 2.0 mg/kg
arm group type: Experimental
description: Three treatment cycles, intravenous infusion of Promitil
arm group label: Cohort E: Promitil 2.5 mg/kg
arm group type: Experimental
description: Three treatment cycles, intravenous infusion of Promitil
arm group label: Cohort F: Promitil 3.0 mg/kg
arm group type: Experimental
description: Three treatment cycles, intravenous infusion of Promitil
arm group label: Cohort G: Promitil 3.5 mg/kg
arm group type: Experimental
description: Three treatment cycles, intravenous infusion of Promitil
arm group label: Cohort H: Promitil 4.0 mg/kg
arm group type: Experimental
description: Three treatment cycles, intravenous infusion of Promitil
arm group label: Expanded Cohort
arm group type: Experimental
description: Patients treated with the selected RP2D of PROMITIL (3 mg/kg) intravenously administered on their first cycle and reduced dose of 2 mg/kg from cycle 2 and onwards.
Only for mCRC patients.
arm group label: Combination Cohort
arm group type: Experimental
description: Patients treated with one cycle of 2.5mg/kg Promitil day 1 together with Capecitabine 1,000 mg bid po days 1-21 followed by two cycles of 2.0 mg/kg Promitil day 1 together with Capecitabine 1,000 mg bid po days 1-21, at four-week intervals.
Only for mCRC patients.
arm group label: Triple combination Cohort
arm group type: Experimental
description: Patients treated with one cycle of 2mg/kg Promitil I.v and 5 mg/kg Bevacizumab i.v on day 1 together with Capecitabine 1,000 mg bid p.o days 1-14 at four-week intervals.
Only for mCRC patients.
arm group label: 3 Weekly Cohort
arm group type: Experimental
description: Patients treated with one cycle of 2mg/kg Promitil I.v and 7.5 mg/kg Bevacizumab i.v on day 1 together at three-week intervals.
Only for mCRC patients.
intervention type: Drug
intervention name: Promitil
description: 2 mg/kg dose IV
arm group label: 3 Weekly Cohort
arm group label: Cohort A: Promitil 0.5 mg/kg
arm group label: Cohort B: Promitil 1.0 mg/kg
arm group label: Cohort C: Promitil 1.5 mg/kg
arm group label: Cohort D: Promitil 2.0 mg/kg
arm group label: Cohort E: Promitil 2.5 mg/kg
arm group label: Cohort F: Promitil 3.0 mg/kg
arm group label: Cohort G: Promitil 3.5 mg/kg
arm group label: Cohort H: Promitil 4.0 mg/kg
arm group label: Combination Cohort
arm group label: Expanded Cohort
arm group label: Triple combination Cohort
intervention type: Drug
intervention name: Capecitabine
description: 1000 mg dose BID PO for days 1-21 for Combination Cohort and on day 1-14 on Triple combination Cohort
arm group label: Combination Cohort
arm group label: Triple combination Cohort
other name: Xeloda
intervention type: Drug
intervention name: Bevacizumab
description: for Triple combination cohort an IV dose of 5 mg/kg on day 1 at 4 week interval. For the 3 weekly cohort an IV dose of 7.5 mg/kg at 3 week interval.
arm group label: 3 Weekly Cohort
arm group label: Triple combination Cohort
other name: Avastin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: Israel
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Colorectal Neoplasms
mesh term: Bevacizumab
mesh term: Capecitabine