<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/NCT03763851</url>
  </required_header>
  <id_info>
    <org_study_id>PPP005-Ph2/3-01</org_study_id>
    <nct_id>NCT03763851</nct_id>
  </id_info>
  <brief_title>Cannabis Oil and Radiation Therapy for the Management of Pain</brief_title>
  <official_title>Cannabis Oil and Radiation Therapy for the Management of Pain: Assessment of Safety and Efficacy in a Randomized, Double-blind Placebo-controlled Phase II/III Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tetra Bio-Pharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Santé Cannabis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>McGill University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Tetra Bio-Pharma</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this innovative approach seeking effective therapeutic strategies, the investigators are&#xD;
      proposing to test the effectiveness of medical cannabis oil as an adjunct to palliative&#xD;
      Radiation Therapy (RT) and Best Supportive Care to alleviate cancer pain that was only&#xD;
      partially relieved with conventional medications. Furthermore, the investigators will assess&#xD;
      the effect of medical cannabis oil on health-related quality of life and symptoms that are&#xD;
      frequently associated with metastatic cancers including fatigue, anxiety, depression,&#xD;
      insomnia and decreased appetite. The safety profile of medical cannabis oil with respect to&#xD;
      prolonged use of more than two weeks of administration, concomitant medication use and&#xD;
      palliative RT will also be examined.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a 6-week randomized, double-blind, placebo-controlled, parallel group design trial&#xD;
      followed by an open-label extension phase of 12 weeks, to evaluate tolerability of medical&#xD;
      cannabis oil to reduce chronic pain intensity.&#xD;
&#xD;
      Consecutive adult patients between the ages of 18 and 75, male and female, with cancer pain,&#xD;
      with an average weekly pain intensity score greater than 4 on the 11 points Numerical Rate&#xD;
      Scale (NRS), will be prospectively recruited and invited to participate in this trial.&#xD;
&#xD;
      Informed consent will be obtained by a Research Assistant.&#xD;
&#xD;
      After baseline documentation with standardized scales, patients will be randomized to one of&#xD;
      two parallel groups:&#xD;
&#xD;
        -  Cannabis group: Delta-9 Tetrahydrocannabidiol (THC) /Cannabidiol (CBD) ratio 1:1 capsule&#xD;
&#xD;
        -  Placebo group: Placebo capsule&#xD;
&#xD;
        -  All patients will receive palliative RT to the symptomatic site. Patients will have a&#xD;
           dose titration phase during the first week. The dose escalation will allow patients to&#xD;
           adapt to the potential adverse effects (AEs) of the medical cannabis.&#xD;
&#xD;
      Follow-up visits either in person or by phone will be at 1 week, 3 weeks and 6 weeks of&#xD;
      treatment.&#xD;
&#xD;
      At the end of the first phase of the study, patients who wish to participate in the&#xD;
      open-label extension phase will have the option to continue in the same treatment regimen.&#xD;
      For the placebo group, patients will have the option to receive the active treatment during&#xD;
      the 12-week open-label phase if the study physician feels it may potentially provide&#xD;
      benefits. Similarly, the dose will be titrated up in the placebo group who wants to receive&#xD;
      the active drug in the extension program.&#xD;
&#xD;
      The open-label phase is 12 weeks long. For this open-label extension phase the follow-up&#xD;
      visits will be done after 4 weeks and 12 weeks of treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    due to mycotoxin potential contamination of one lot of study drug&#xD;
  </why_stopped>
  <start_date type="Actual">March 14, 2018</start_date>
  <completion_date type="Actual">November 30, 2018</completion_date>
  <primary_completion_date type="Actual">November 30, 2018</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cancer pain intensity assessed by Pain Intensity (PI) measurement a numerical rating scale</measure>
    <time_frame>Change (a reduction of 30% in pain intensity) in pain intensity after medical cannabis oil administration compared to placebo at 6 weeks compared to baseline</time_frame>
    <description>Pain Intensity (PI) measurement a Numerical Rating Scale (zero= no pain and 10= pain as bad as it can be).&#xD;
A reduction of PI ≥ 33% will be considered as a clinically important level of pain relief</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cancer pain quality using the Brief Pain Inventory-SF (BPI-SF)</measure>
    <time_frame>The measurements will be completed at baseline before initiating treatment and at week 1, week 3 and week 6 after starting treatment</time_frame>
    <description>The BPI-SF consists of nine questions; eight have a single response, and Question 9 is subdivided into seven parts. The Total BPI for Question 9 is the unweighted sum of the seven assessments and represents the effect of pain</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Impact of medical cannabis oil combined with radiation treatment on HRQoL as measured by the EQ-5D-5L</measure>
    <time_frame>at baseline, 1-week, 3-week, and 6-week follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional status assessed by the Functional Assessment of Cancer Therapy for Prostate patients (FACT-P).</measure>
    <time_frame>The measurements will be completed at baseline before initiating treatment and at week 1, week 3 and week 6 after starting treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fatigue burden assessed by the Brief Fatigue Inventory (BFI).</measure>
    <time_frame>The measurements will be completed at baseline before initiating treatment and at week 1, week 3 and week 6 after starting treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive status assessed by the Mini-Cog</measure>
    <time_frame>The measurements will be completed at baseline before initiating treatment and at week 1, week 3 and week 6 after starting treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Metastatic Prostate Cancer</condition>
  <condition>Lung Cancer</condition>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Cannabis group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Delta-9 Tetrahydrocannabidiol (THC) /Cannabidiol (CBD) ratio 1:1 capsule&#xD;
These capsules contain different cannabis formulations with low-dose and high-dose preparations according to the treatment group:&#xD;
Cannabis group low-dose capsule contains THC 1mg CBD 1mg&#xD;
Cannabis group high-dose capsule contains THC 2.5mg CBD 2.5mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo capsule will have no cannabis, it will look identical to the active treatment capsule, and it will also be prepared in &quot;low-dose&quot; and &quot;high-dose&quot; presentations.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Active PPP005</intervention_name>
    <description>Group assigned to active PPP005 in the randomized placebo-controlled trial</description>
    <arm_group_label>Cannabis group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiotherapy</intervention_name>
    <description>Palliative RadioTherapy to the symptomatic site</description>
    <arm_group_label>Cannabis group</arm_group_label>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ability to consent to the study-specific written consent form, in English or French;&#xD;
&#xD;
          2. Adult patients, male and female between the ages of 18 and 75 (inclusively);&#xD;
&#xD;
          3. Patients with confirmed diagnosis of metastatic carcinoma of the prostate, lung or&#xD;
             breast;&#xD;
&#xD;
               1. No limitation with respect to number of metastases (bone and visceral);&#xD;
&#xD;
               2. Location of metastases limited to exclude any brain metastases&#xD;
&#xD;
          4. Patients experiencing an average weekly pain intensity score of 4 or higher on a 11&#xD;
             points NRS and requiring palliative RT;&#xD;
&#xD;
          5. KPS of equal or higher than 60;&#xD;
&#xD;
          6. Subject agreed to follow the protocol;&#xD;
&#xD;
          7. Patients who are referred to receive RT and are non-regular users of cannabis in any&#xD;
             form (three times per week or more) and are willing to abstain for 1 week prior and&#xD;
             during the study;&#xD;
&#xD;
          8. Patients receiving opioids and other concomitant pain medications must have a stable&#xD;
             dose for the last 15 days;&#xD;
&#xD;
          9. Normal cognitive status according to MiniCog;&#xD;
&#xD;
         10. Normal liver function (defined as aspartate aminotransferase 10-40 U/L and alanine&#xD;
             aminotransferase 7-56 U/L)&#xD;
&#xD;
         11. Normal renal function (defined as serum creatinine level &lt;133 µmol/L and Estimated&#xD;
             Glomerular Filtration Rate (eGFR) equal or higher than 60)&#xD;
&#xD;
         12. Negative result on βhuman chorionic gonadotropin pregnancy test (if applicable)&#xD;
&#xD;
         13. A female volunteer must meet one of the following criteria:&#xD;
&#xD;
               1. If of childbearing potential - agrees to use one of the accepted contraceptive&#xD;
                  regimens from at least 28 days prior to the first drug administration, during the&#xD;
                  study and for at least 60 days after the last dose.&#xD;
&#xD;
               2. If of non-childbearing potential - should be surgically sterile or in a&#xD;
                  menopausal state&#xD;
&#xD;
         14. A male volunteer with sexual partners who are pregnant, possibly pregnant, or who&#xD;
             could become pregnant must be surgically sterile or agrees to use one of the accepted&#xD;
             contraceptive regimens from first drug administration until 3 months after the last&#xD;
             drug administration.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who are unable to consent or to comply with the instructions of the study;&#xD;
&#xD;
          2. Patients suffering primarily from pain not related to cancer;&#xD;
&#xD;
          3. KPS of &lt; 60;&#xD;
&#xD;
          4. Previous serious adverse event or hypersensitivity to cannabis or cannabinoids;&#xD;
&#xD;
          5. Presence of significant cardiac disease (history of unstable ischemic heart disease,&#xD;
             heart failure, severe and uncontrolled hypertension) that, in the opinion of the&#xD;
             investigator, would put the patient at risk of a clinically significant arrhythmia or&#xD;
             myocardial infarction;&#xD;
&#xD;
          6. Current substance use disorder according to the Diagnostic and Statistical Manual of&#xD;
             Mental Disorders Fifth Edition (DSM 5);&#xD;
&#xD;
          7. Life-time history of dependence on cannabis or diagnosis of cannabis use disorder&#xD;
             (CUD) according to the DSM 5;&#xD;
&#xD;
          8. Life-time history of DSM 5 schizophrenia, bipolar disorder, or previous psychosis with&#xD;
             or intolerance to cannabinoids;&#xD;
&#xD;
          9. Current suicidal ideation according to the Columbia-Suicide Severity Rating Scale&#xD;
             (C-SSRS);&#xD;
&#xD;
         10. Pregnant, breast-feeding or female patients of child-bearing potential and male&#xD;
             patients whose partner is of child-bearing potential, unless willing to ensure that&#xD;
             they or their partner use effective contraception;&#xD;
&#xD;
         11. Hepatic impairment (aspartate aminotransferase more than three times normal) or renal&#xD;
             function impairment (serum creatinine level &gt;133 µmol/L.&#xD;
&#xD;
         12. Cognitive impairment according to MiniCog;&#xD;
&#xD;
         13. Current use of cannabis in any form more than 3 times per week or use of&#xD;
             cannabinoid-based medications within 7 days of study entry and refusal to abstain for&#xD;
             the duration of the study;&#xD;
&#xD;
         14. Positive blood test for cannabinoids at screening or positive urine screening for&#xD;
             other potential abuse substances (e.g. alcohol, cocaine, amphetamines and&#xD;
             methamphetamines, unprescribed opioids);&#xD;
&#xD;
         15. Participation in another clinical trial within 30 days of screening visit&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tamim Niazi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Jewish General Hospital, McGill University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jean Zigby, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Jewish General Hospital, McGill University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sante Cannabis</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>November 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>March 10, 2020</last_update_submitted>
  <last_update_submitted_qc>March 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 12, 2020</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>Prostatic Neoplasms</mesh_term>
    <mesh_term>Marijuana Abuse</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03763851
org study id: PPP005-Ph2/3-01
nct id: NCT03763851
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
In this innovative approach seeking effective therapeutic strategies, the investigators are
      proposing to test the effectiveness of medical cannabis oil as an adjunct to palliative
      Radiation Therapy (RT) and Best Supportive Care to alleviate cancer pain that was only
      partially relieved with conventional medications. Furthermore, the investigators will assess
      the effect of medical cannabis oil on health-related quality of life and symptoms that are
      frequently associated with metastatic cancers including fatigue, anxiety, depression,
      insomnia and decreased appetite. The safety profile of medical cannabis oil with respect to
      prolonged use of more than two weeks of administration, concomitant medication use and
      palliative RT will also be examined.
This is a 6-week randomized, double-blind, placebo-controlled, parallel group design trial
      followed by an open-label extension phase of 12 weeks, to evaluate tolerability of medical
      cannabis oil to reduce chronic pain intensity.

      Consecutive adult patients between the ages of 18 and 75, male and female, with cancer pain,
      with an average weekly pain intensity score greater than 4 on the 11 points Numerical Rate
      Scale (NRS), will be prospectively recruited and invited to participate in this trial.

      Informed consent will be obtained by a Research Assistant.

      After baseline documentation with standardized scales, patients will be randomized to one of
      two parallel groups:

        -  Cannabis group: Delta-9 Tetrahydrocannabidiol (THC) /Cannabidiol (CBD) ratio 1:1 capsule

        -  Placebo group: Placebo capsule

        -  All patients will receive palliative RT to the symptomatic site. Patients will have a
           dose titration phase during the first week. The dose escalation will allow patients to
           adapt to the potential adverse effects (AEs) of the medical cannabis.

      Follow-up visits either in person or by phone will be at 1 week, 3 weeks and 6 weeks of
      treatment.

      At the end of the first phase of the study, patients who wish to participate in the
      open-label extension phase will have the option to continue in the same treatment regimen.
      For the placebo group, patients will have the option to receive the active treatment during
      the 12-week open-label phase if the study physician feels it may potentially provide
      benefits. Similarly, the dose will be titrated up in the placebo group who wants to receive
      the active drug in the extension program.

      The open-label phase is 12 weeks long. For this open-label extension phase the follow-up
      visits will be done after 4 weeks and 12 weeks of treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Cancer pain intensity assessed by Pain Intensity (PI) measurement a numerical rating scale
time frame: Change (a reduction of 30% in pain intensity) in pain intensity after medical cannabis oil administration compared to placebo at 6 weeks compared to baseline
description: Pain Intensity (PI) measurement a Numerical Rating Scale (zero= no pain and 10= pain as bad as it can be).
A reduction of PI ≥ 33% will be considered as a clinically important level of pain relief
measure: Cancer pain quality using the Brief Pain Inventory-SF (BPI-SF)
time frame: The measurements will be completed at baseline before initiating treatment and at week 1, week 3 and week 6 after starting treatment
description: The BPI-SF consists of nine questions; eight have a single response, and Question 9 is subdivided into seven parts. The Total BPI for Question 9 is the unweighted sum of the seven assessments and represents the effect of pain
measure: Impact of medical cannabis oil combined with radiation treatment on HRQoL as measured by the EQ-5D-5L
time frame: at baseline, 1-week, 3-week, and 6-week follow-up
measure: Functional status assessed by the Functional Assessment of Cancer Therapy for Prostate patients (FACT-P).
time frame: The measurements will be completed at baseline before initiating treatment and at week 1, week 3 and week 6 after starting treatment
measure: Fatigue burden assessed by the Brief Fatigue Inventory (BFI).
time frame: The measurements will be completed at baseline before initiating treatment and at week 1, week 3 and week 6 after starting treatment
measure: Cognitive status assessed by the Mini-Cog
time frame: The measurements will be completed at baseline before initiating treatment and at week 1, week 3 and week 6 after starting treatment
arm group label: Cannabis group
arm group type: Experimental
description: Delta-9 Tetrahydrocannabidiol (THC) /Cannabidiol (CBD) ratio 1:1 capsule
These capsules contain different cannabis formulations with low-dose and high-dose preparations according to the treatment group:
Cannabis group low-dose capsule contains THC 1mg CBD 1mg
Cannabis group high-dose capsule contains THC 2.5mg CBD 2.5mg
arm group label: Placebo group
arm group type: Placebo Comparator
description: The placebo capsule will have no cannabis, it will look identical to the active treatment capsule, and it will also be prepared in "low-dose" and "high-dose" presentations.
intervention type: Radiation
intervention name: Active PPP005
description: Group assigned to active PPP005 in the randomized placebo-controlled trial
arm group label: Cannabis group
intervention type: Radiation
intervention name: Radiotherapy
description: Palliative RadioTherapy to the symptomatic site
arm group label: Cannabis group
arm group label: Placebo group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Tamim Niazi, MD
role: Principal Investigator
affiliation: Jewish General Hospital, McGill University
last name: Jean Zigby, MD
role: Principal Investigator
affiliation: Jewish General Hospital, McGill University
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Marijuana Abuse
sharing ipd: Undecided