<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/NCT02201381</url>
  </required_header>
  <id_info>
    <org_study_id>Metabolic Cancer 001</org_study_id>
    <nct_id>NCT02201381</nct_id>
  </id_info>
  <brief_title>Study of the Safety, Tolerability and Efficacy of Metabolic Combination Treatments on Cancer</brief_title>
  <acronym>METRICS</acronym>
  <official_title>A Non Randomised, Non Blinded Real World Trial of the Safety, Tolerability and Effectiveness of Metabolic Medicines for the Treatment of Cancer Compared Against Matched Controls</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Health Clinics Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Health Clinics Limited</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the effectiveness of a regimen of selected&#xD;
      metabolic treatments for patients with cancer in a real world setting and to conduct&#xD;
      exploratory analysis on the relationship between the degree of response and changes in&#xD;
      biochemical markers (such as glucose and lipid levels).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      *This study has been designed to collect data prospectively and to retrospectively analyse&#xD;
      data on the metabolic treatments within the cancer clinic. The retrospective study is&#xD;
      ongoing, while the prospective study has not yet started.*&#xD;
&#xD;
      This is a real world study since this gives the best opportunity to properly examine the&#xD;
      effect of multi-drug regimens in representative populations. Including a standard of care arm&#xD;
      is inappropriate, in a population in which that standard of care has already been shown to be&#xD;
      ineffective or intolerable.&#xD;
&#xD;
      Patients will be sent to the study clinic directly by their Health Care Professionals&#xD;
      (&quot;HCP's&quot;) .&#xD;
&#xD;
      The study will consist of a pre-screening visit to determine eligibility for inclusion into&#xD;
      the study, an initiation visit and then a follow up visit every three months thereafter. If&#xD;
      required, unscheduled visits may take place. Day 0 (baseline) for each patient will be the&#xD;
      initiation visit when study treatment is started.&#xD;
&#xD;
      Prior to conducting any study-related procedures, subjects will provide written informed&#xD;
      consent, eligibility will be assessed, a medical history and past medical records will be&#xD;
      taken and vital signs will be measured. These records will include the stage of their&#xD;
      disease, response to previous cancer therapy, their prior and current medications and any&#xD;
      specific regimen they are currently on for their cancer. If prior medical records do not&#xD;
      contain sufficient information to determine a baseline for the patient, additional blood&#xD;
      tests and scans will be undertaken as appropriate.&#xD;
&#xD;
      Patients will be monitored quarterly thereafter when blood tests (e.g. safety parameters,&#xD;
      glucose, cholesterol, immune response and cancer markers where applicable) and scans (where&#xD;
      applicable) will be taken.&#xD;
&#xD;
      All patients will be on the same drug regimen (see below) at the same doses throughout the&#xD;
      study. All patients will be followed up until they choose to leave the study, or death.&#xD;
&#xD;
      Data from all patients recruited to the study will be analysed using an Intention-to-treat&#xD;
      (ITT) philosophy, so data will be included in the primary analysis irrespective of whether&#xD;
      the dose regimen was followed throughout the study. If appropriate, and numbers allow,&#xD;
      analysis will also be conducted on the Per Protocol population, comprising those patients who&#xD;
      adhere to the regimen as prescribed.&#xD;
&#xD;
      Survival analysis methods will be used to estimate the Overall survival associated with the&#xD;
      study regimen for each type of cancer. These estimates will be interpreted in the light of&#xD;
      data obtained from the literature, and from eliciting expert opinion. Bayesian methods may be&#xD;
      used where appropriate.&#xD;
&#xD;
      Tumour response, where applicable, will be summarised in tables and graphs. Estimates of&#xD;
      response rates will be presented for each cancer type with confidence intervals.&#xD;
&#xD;
      The relationship between changes in biochemistry values (glucose, lipids) and efficacy&#xD;
      outcomes (Progression Free Survival (PFS), Overall Survival (OS) and HRQoL) will be&#xD;
      investigated graphically, or using other methods as appropriate.&#xD;
&#xD;
      Further exploratory analysis to investigate the effects of other factors such as age , ethnic&#xD;
      backgrounds , cancer stage, and response to prior therapy, will also be conducted in order to&#xD;
      try and characterise the profile of patients most likely to benefit from the study regimen.&#xD;
&#xD;
      The characteristics of patients on the regimen and those who do not stay on the regimen, for&#xD;
      whatever reason, will be summarised to see whether there is any observed bias. If&#xD;
      appropriate, methods will be used to adjust for any observed bias, for example using&#xD;
      propensity scores. OS can then be assessed adjusted for this to try and mitigate for any&#xD;
      possible risk of bias which can occur in uncontrolled studies. Furthermore, by enrolling all&#xD;
      eligible patients over a specified time frame, it is hoped that the risk of bias should be&#xD;
      further reduced. In addition, a large number of patients are expected to participate in the&#xD;
      study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Prospective recruitment not possible&#xD;
  </why_stopped>
  <start_date type="Anticipated">May 23, 2022</start_date>
  <completion_date type="Anticipated">September 23, 2027</completion_date>
  <primary_completion_date type="Anticipated">May 23, 2027</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>Matched historical control comparison</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Overall survival for all cancer types and for each cancer type (years and months)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in primary tumour size cancer types and by cancer type.</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Tumour size for all cancer types and for each cancer type. Units of size vary depending on cancer type.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in tumour spread (metastasis)</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Tumour spread (metastasized) to other tissues/organs, for all cancer types and for each cancer type. This is measured as either 0 for no spread or 1 for confirmed spread.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in tumour number</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Tumour number for all cancer types and for each cancer type</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cancer biomarkers (blood, urine or biopsy)</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Cancer biomarkers for all cancer types and for each cancer type. Units of measurement vary depending on the cancer type. When biomarkers, either alone or in combination with other biomarkers, are raised above normal they are seen as predictive of cancer of progression. If returned to normal are indicative of treatment response.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of treatment related adverse events</measure>
    <time_frame>5 years</time_frame>
    <description>Adverse events reported by the subject or their HCP.&#xD;
• Quarterly assessment of routine laboratory tests</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Cancer</condition>
  <condition>Overall Survival</condition>
  <arm_group>
    <arm_group_label>Metabolic Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will take the following treatments and have their data collected from their medical records every 3 months.&#xD;
Oral atorvastatin up to 80mg uid, for study duration.&#xD;
Oral metformin up to 1000mg uid, increased to bid if tolerated after 2 weeks, for study duration.&#xD;
Oral doxycycline 100mg uid, for study duration.&#xD;
Oral Mebendazole 100mg uid, for study duration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metabolic treatment</intervention_name>
    <description>While subjects are being treated with the four metabolic drugs, every 3 months they will bring in their medical records and data will be collected to determine the effect of the intervention</description>
    <arm_group_label>Metabolic Treatment</arm_group_label>
    <other_name>Metformin</other_name>
    <other_name>Atorvastatin</other_name>
    <other_name>Doxycycline</other_name>
    <other_name>Mebendazole</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          1. Male or female 18-85 years old;&#xD;
&#xD;
          2. Diagnosed with cancer and have had such diagnosis confirmed by scan, blood markers&#xD;
             and/or biopsy;&#xD;
&#xD;
          3. Is receiving or will shortly receive standard of care therapy or has completed&#xD;
             standard of care treatment; and&#xD;
&#xD;
          4. Signed and dated written informed consent from the participant or LAR.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating females or females who are planning a pregnancy during the&#xD;
             course of the study;&#xD;
&#xD;
          2. Major organ failure, renal, lung and liver failure;&#xD;
&#xD;
          3. Participants having active liver disease or unexplained persistent elevation of serum&#xD;
             transaminases &gt; 3 times the upper limit of normal;&#xD;
&#xD;
          4. Participants with diabetic ketoacidosis or diabetic pre-coma;&#xD;
&#xD;
          5. Participants with a creatinine clearance &lt; 60mL/min;&#xD;
&#xD;
          6. History of cardiac or respiratory failure;&#xD;
&#xD;
          7. History of recent myocardial infarction;&#xD;
&#xD;
          8. Ileum, colon or stomach part or full removal rendering them unable to take the study&#xD;
             medicines;&#xD;
&#xD;
          9. Unable to eat or keep food or medicines down or is being fed intravenously;&#xD;
&#xD;
         10. Is too frail and weak to withstand the study medicines in the opinion of the study&#xD;
             doctor;&#xD;
&#xD;
         11. Is Unlikely to survive more than 1 month under standard of care, in the opinion of the&#xD;
             study doctor&#xD;
&#xD;
         12. Hypersensitivity to any of the treatment drugs or excipients;&#xD;
&#xD;
         13. If the patient is on any medicines contraindicated with the study medicines (see&#xD;
             Appendix 3);&#xD;
&#xD;
         14. Mentally incapacitated and no guardian able to sign on patients Clinical study&#xD;
             protocol, version 5.0 METRICS TRIAL, Metabolic Cancer 001 5th Apr 2016 Confidential&#xD;
             Page 5 of 65 behalf;&#xD;
&#xD;
         15. History or presence of alcohol or substance abuse;&#xD;
&#xD;
         16. Participation in a clinical trial of an investigational medicinal product that is&#xD;
             viewed by the Study Physician to be a significant risk to the participant's safety;&#xD;
&#xD;
         17. Direct employee of the study site.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Samir Agrawal, MRCP FRCPath</last_name>
    <role>Principal Investigator</role>
    <affiliation>Care Oncology Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Care Oncology Clinic</name>
      <address>
        <city>London</city>
        <zip>W1G 9PP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>July 14, 2022</last_update_submitted>
  <last_update_submitted_qc>July 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cancer</keyword>
  <keyword>Cancer Treatments</keyword>
  <keyword>Cancer Palliative Care</keyword>
  <keyword>Metabolic</keyword>
  <keyword>Metabolism</keyword>
  <keyword>Existing Medicines</keyword>
  <keyword>Licensed Medicines</keyword>
  <keyword>Real World</keyword>
  <keyword>Breast Cancer</keyword>
  <keyword>Triple Negative Breast Cancer</keyword>
  <keyword>Colon Cancer</keyword>
  <keyword>Prostrate Cancer</keyword>
  <keyword>Brain Cancer</keyword>
  <keyword>Ovarian Cancer</keyword>
  <keyword>Pancreatic Cancer</keyword>
  <keyword>AML</keyword>
  <keyword>CML</keyword>
  <keyword>Leukemea</keyword>
  <keyword>Metformin</keyword>
  <keyword>Statins</keyword>
  <keyword>Mebendazole</keyword>
  <keyword>Doxycycline</keyword>
  <keyword>Ibuprofen</keyword>
  <keyword>Metastatic</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Doxycycline</mesh_term>
    <mesh_term>Mebendazole</mesh_term>
    <mesh_term>Atorvastatin</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/NCT02201381
org study id: Metabolic Cancer 001
nct id: NCT02201381
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to determine the effectiveness of a regimen of selected
      metabolic treatments for patients with cancer in a real world setting and to conduct
      exploratory analysis on the relationship between the degree of response and changes in
      biochemical markers (such as glucose and lipid levels).
*This study has been designed to collect data prospectively and to retrospectively analyse
      data on the metabolic treatments within the cancer clinic. The retrospective study is
      ongoing, while the prospective study has not yet started.*

      This is a real world study since this gives the best opportunity to properly examine the
      effect of multi-drug regimens in representative populations. Including a standard of care arm
      is inappropriate, in a population in which that standard of care has already been shown to be
      ineffective or intolerable.

      Patients will be sent to the study clinic directly by their Health Care Professionals
      ("HCP's") .

      The study will consist of a pre-screening visit to determine eligibility for inclusion into
      the study, an initiation visit and then a follow up visit every three months thereafter. If
      required, unscheduled visits may take place. Day 0 (baseline) for each patient will be the
      initiation visit when study treatment is started.

      Prior to conducting any study-related procedures, subjects will provide written informed
      consent, eligibility will be assessed, a medical history and past medical records will be
      taken and vital signs will be measured. These records will include the stage of their
      disease, response to previous cancer therapy, their prior and current medications and any
      specific regimen they are currently on for their cancer. If prior medical records do not
      contain sufficient information to determine a baseline for the patient, additional blood
      tests and scans will be undertaken as appropriate.

      Patients will be monitored quarterly thereafter when blood tests (e.g. safety parameters,
      glucose, cholesterol, immune response and cancer markers where applicable) and scans (where
      applicable) will be taken.

      All patients will be on the same drug regimen (see below) at the same doses throughout the
      study. All patients will be followed up until they choose to leave the study, or death.

      Data from all patients recruited to the study will be analysed using an Intention-to-treat
      (ITT) philosophy, so data will be included in the primary analysis irrespective of whether
      the dose regimen was followed throughout the study. If appropriate, and numbers allow,
      analysis will also be conducted on the Per Protocol population, comprising those patients who
      adhere to the regimen as prescribed.

      Survival analysis methods will be used to estimate the Overall survival associated with the
      study regimen for each type of cancer. These estimates will be interpreted in the light of
      data obtained from the literature, and from eliciting expert opinion. Bayesian methods may be
      used where appropriate.

      Tumour response, where applicable, will be summarised in tables and graphs. Estimates of
      response rates will be presented for each cancer type with confidence intervals.

      The relationship between changes in biochemistry values (glucose, lipids) and efficacy
      outcomes (Progression Free Survival (PFS), Overall Survival (OS) and HRQoL) will be
      investigated graphically, or using other methods as appropriate.

      Further exploratory analysis to investigate the effects of other factors such as age , ethnic
      backgrounds , cancer stage, and response to prior therapy, will also be conducted in order to
      try and characterise the profile of patients most likely to benefit from the study regimen.

      The characteristics of patients on the regimen and those who do not stay on the regimen, for
      whatever reason, will be summarised to see whether there is any observed bias. If
      appropriate, methods will be used to adjust for any observed bias, for example using
      propensity scores. OS can then be assessed adjusted for this to try and mitigate for any
      possible risk of bias which can occur in uncontrolled studies. Furthermore, by enrolling all
      eligible patients over a specified time frame, it is hoped that the risk of bias should be
      further reduced. In addition, a large number of patients are expected to participate in the
      study.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Matched historical control comparison
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: up to 5 years
description: Overall survival for all cancer types and for each cancer type (years and months)
measure: Change in primary tumour size cancer types and by cancer type.
time frame: up to 5 years
description: Tumour size for all cancer types and for each cancer type. Units of size vary depending on cancer type.
measure: Change in tumour spread (metastasis)
time frame: up to 5 years
description: Tumour spread (metastasized) to other tissues/organs, for all cancer types and for each cancer type. This is measured as either 0 for no spread or 1 for confirmed spread.
measure: Change in tumour number
time frame: up to 5 years
description: Tumour number for all cancer types and for each cancer type
measure: Change in cancer biomarkers (blood, urine or biopsy)
time frame: up to 5 years
description: Cancer biomarkers for all cancer types and for each cancer type. Units of measurement vary depending on the cancer type. When biomarkers, either alone or in combination with other biomarkers, are raised above normal they are seen as predictive of cancer of progression. If returned to normal are indicative of treatment response.
measure: Incidence of treatment related adverse events
time frame: 5 years
description: Adverse events reported by the subject or their HCP.
• Quarterly assessment of routine laboratory tests
arm group label: Metabolic Treatment
arm group type: Experimental
description: Subjects will take the following treatments and have their data collected from their medical records every 3 months.
Oral atorvastatin up to 80mg uid, for study duration.
Oral metformin up to 1000mg uid, increased to bid if tolerated after 2 weeks, for study duration.
Oral doxycycline 100mg uid, for study duration.
Oral Mebendazole 100mg uid, for study duration.
intervention type: Drug
intervention name: Metabolic treatment
description: While subjects are being treated with the four metabolic drugs, every 3 months they will bring in their medical records and data will be collected to determine the effect of the intervention
arm group label: Metabolic Treatment
other name: Metformin
other name: Atorvastatin
other name: Doxycycline
other name: Mebendazole
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Samir Agrawal, MRCP FRCPath
role: Principal Investigator
affiliation: Care Oncology Clinic
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Metformin
mesh term: Doxycycline
mesh term: Mebendazole
mesh term: Atorvastatin
sharing ipd: No