xml: <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/NCT05969314</url>
    </required_header>
    <id_info>
      <org_study_id>TMH Project No. 3386</org_study_id>
      <secondary_id>CTRI/2020/06/020649</secondary_id>
      <nct_id>NCT05969314</nct_id>
    </id_info>
    <brief_title>To Check Safety of Ayurvedic Oral Cannabis in Breast and Head and Neck Cancer</brief_title>
    <official_title>Phase I Study of Safety and Feasibility of Ayurvedic Oral Cannabis Preparation in the Peri-operative Period in Breast and Oral Cavity Squamous Cell Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tata Memorial Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Tata Memorial Hospital</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>
        Phase 1 study to assess the pharmacokinetic availability and safety and tolerability profile&#xD;
        of one such ayurvedic preparation which contains 5 mg THC:CBD 1:1 preparation. Other than the&#xD;
        PK profile, we will also be studying its effect on gene expression profiling of the breast&#xD;
        and head neck oral cavity squamous cell carcinoma tissue.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The ancient Ayurvedic medicine obtained from Cannabis sativa plant has recently been&#xD;
        re-explored for its anti-inflammatory and anti-cancer potential. Various laboratory and&#xD;
        preclinical studies have proven its anti-cancer activity and its effect on all the hallmarks&#xD;
        of cancer. Anecdotal clinical evidence has shown regression of tumours with ingestion of such&#xD;
        medicinal cannabis. A randomized controlled trial in Glioblastoma Multiforme, a kind of brain&#xD;
        tumour, shows improvement in disease free survival when temozolamide was combined with&#xD;
        Cannabis spray called Sativex.&#xD;
  &#xD;
        However, because of lack of systematic, large volume studies, the evidence is slow to emerge.&#xD;
        We have previously seen changes related to NF-kb (inflammation) and AP1 (acute&#xD;
        hypoxia/stress) pathway genes within the tumour tissue as assessed by transcriptomic analysis&#xD;
        (Yet unpublished data). There is laboratory evidence to suggest that the changes induced in&#xD;
        the AP1 pathway during surgery can be ameliorated by cannabis treatment. We intend to explore&#xD;
        this anticancer potential of C sativa herbal preparation in the pre-operative setting in&#xD;
        breast and head and neck cancer patients. Hence, we are proposing a phase 1 study to assess&#xD;
        the pharmacokinetic availability and safety and tolerability profile of one such ayurvedic&#xD;
        preparation which contains 5 mg THC:CBD 1:1 preparation. Other than the PK profile, we will&#xD;
        also be studying its effect on gene expression profiling of the breast and head neck oral&#xD;
        cavity squamous cell carcinoma tissue.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">June 8, 2022</start_date>
    <completion_date type="Anticipated">December 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
    <phase>Phase 1</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>To determine the maximum tolerated dose (MTD). First 3 patients will receive the study preparation once a day at 9 am (+/- 60 min) (i.e 5 mg of CBD and 5 mg of THC in a 400 mg capsule). Subsequent cohorts will be administered doses of 10 (10 mg of THC and CBD each), 20 (20+20) and 30 (30+30) mg in a classical 3+3 dose escalation study. Briefly, 3 patients will be enrolled at dose level. Dose escalation to the next dose level will continue as long no DLT is observed in 3 patients (the incidence of DLT is ≤ 1/6) In any cohort, if 1/3 patients develop DLT, then 3 more patients will be added at that dose. The dose level at which more than 1/6 patients develop DLT will be considered the MTD and no further escalation will be done beyond the MTD. One dose level below the MTD will be considered for future trials. If MTD is not achieved, the highest dose (30+30) will be considered for future trials. If toxicity is seen at 30 mg, then de-escalation to 25 mg may be considered.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To establish safe dose of oral cannabis preparation</measure>
      <time_frame>From day 1 of IP dosing till 28 days .</time_frame>
      <description>Number of participants with treatment-related adverse events with respect to cardiovascular, central nervous system and psychotropic of cannabis as assessed by CTCAE v4.0</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetic profiling</measure>
      <time_frame>1.Pre operative day 1 to 5 - one each day before cannabinoid dosing, after dosing 30 minutes, 1 hour, 2 hour and 8 hour. 2. On day of surgery - Before and after the surgery 3. Post operative day 1 , day 2, day 3 and day 14</time_frame>
      <description>Blood samples collected during the administration of the IP for 5 days and up to 72 hours after surgery.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Biomarker analysis- Transcitpomics</measure>
      <time_frame>A baseline pre-cannabis tumor tissue sample will be collected before starting IP(day 0). Further blood and tumor as well as adjacent normal tissue samples will be collected during surgery (day6).</time_frame>
      <description>Tumor and normal tissue samples.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Actual">12</enrollment>
    <condition>Breast Cancer</condition>
    <condition>Oral Cancer</condition>
    <arm_group>
      <arm_group_label>Cannabis</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Cannabis capsules containing 5 mg of THC and CBD each or 2.5 mg of THC and CBD each.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cannabis capsules</intervention_name>
      <description>Cannabis capsules containing 5 mg of THC and CBD each or 2.5 mg of THC and CBD each.</description>
      <arm_group_label>Cannabis</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Histopathologically proven patients of breast or oral cavity SCC&#xD;
  &#xD;
            2. Age &gt; 18 and &lt; 65&#xD;
  &#xD;
            3. Operable cancers planned to undergo upfront curative surgery&#xD;
  &#xD;
            4. Patient fit for surgery (ASA Grade I / II)&#xD;
  &#xD;
            5. Patient Voluntarily willing to give consent for study&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Planned for any other pre or peri-operative intervention such as neoadjuvant&#xD;
               chemotherapy or targeted therapy or radiation&#xD;
  &#xD;
            2. Presence of medical disease such as pulmonary, renal, liver, gastro-intestinal disease&#xD;
               which may interfere with any study specific procedure (deranged renal parameters &gt; 1.5&#xD;
               times normal range or deranged liver function tests such as &gt; 2.5 times raised liver&#xD;
               enzymes)&#xD;
  &#xD;
            3. History of substance abuse (including cannabis-related products) or alcohol abuse&#xD;
  &#xD;
            4. Personal history of psychiatric disease or Significant family history of psychiatric&#xD;
               disease&#xD;
  &#xD;
            5. Pregnancy and/or lactation&#xD;
  &#xD;
            6. Patients currently (within last 14 days before consenting) on other CNS depressants&#xD;
               such as alcohol, barbiturates, benozodiazapines (like diazepam, alprazolam etc)&#xD;
  &#xD;
            7. Patients on other medications which will likely have a drug interaction with cannabis-&#xD;
               such as clozapine, duloxetine, naproxen, cyclobenzaprine, olanzapine, haloperidol, and&#xD;
               chlorpromazine, macrolides, calcium channel blockers, benzodiazepines, cyclosporine,&#xD;
               sildenafil (and other PDE5 inhibitors), antihistamines, haloperidol, antiretrovirals&#xD;
  &#xD;
            8. Any other illness or abnormal laboratory investigations which the investigator&#xD;
               considers as making the patients ineligible for the study&#xD;
  &#xD;
            9. Any patient with positive HIV, HBsAg, HCV status&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Rajendra A Badwe, MS</last_name>
      <role>Principal Investigator</role>
      <affiliation>Director, Tata Memorial Centre</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Tata Memorial Center</name>
        <address>
          <city>Mumbai</city>
          <state>Maharashtra</state>
          <zip>400012</zip>
          <country>India</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Tata Memorial Hospital</name>
        <address>
          <city>Mumbai</city>
          <state>Maharastra</state>
          <zip>400012</zip>
          <country>India</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>India</country>
    </location_countries>
    <reference>
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      <citation>Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, Keurentjes JC, Lang S, Misso K, Ryder S, Schmidlkofer S, Westwood M, Kleijnen J. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73. doi: 10.1001/jama.2015.6358. Erratum In: JAMA. 2015 Aug 4;314(5):520. JAMA. 2015 Aug 25;314(8):837. JAMA. 2015 Dec 1;314(21):2308. JAMA. 2016 Apr 12;315(14):1522.</citation>
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      <citation>Vara D, Salazar M, Olea-Herrero N, Guzman M, Velasco G, Diaz-Laviada I. Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy. Cell Death Differ. 2011 Jul;18(7):1099-111. doi: 10.1038/cdd.2011.32. Epub 2011 Apr 8. Erratum In: Cell Death Differ. 2011 Jul;18(7):1237.</citation>
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      <citation>Bhattacharyya S, Morrison PD, Fusar-Poli P, Martin-Santos R, Borgwardt S, Winton-Brown T, Nosarti C, O' Carroll CM, Seal M, Allen P, Mehta MA, Stone JM, Tunstall N, Giampietro V, Kapur S, Murray RM, Zuardi AW, Crippa JA, Atakan Z, McGuire PK. Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology. 2010 Feb;35(3):764-74. doi: 10.1038/npp.2009.184. Epub 2009 Nov 18.</citation>
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    </reference>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>May 31, 2022</study_first_submitted>
    <study_first_submitted_qc>July 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 22, 2023</last_update_submitted>
    <last_update_submitted_qc>July 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Tata Memorial Hospital</investigator_affiliation>
      <investigator_full_name>Dr Rajendra A. Badwe</investigator_full_name>
      <investigator_title>Doctor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Mouth Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05969314
  org study id: TMH Project No. 3386
  secondary id: CTRI/2020/06/020649
  nct id: NCT05969314
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Phase 1 study to assess the pharmacokinetic availability and safety and tolerability profile
        of one such ayurvedic preparation which contains 5 mg THC:CBD 1:1 preparation. Other than the
        PK profile, we will also be studying its effect on gene expression profiling of the breast
        and head neck oral cavity squamous cell carcinoma tissue.
  The ancient Ayurvedic medicine obtained from Cannabis sativa plant has recently been
        re-explored for its anti-inflammatory and anti-cancer potential. Various laboratory and
        preclinical studies have proven its anti-cancer activity and its effect on all the hallmarks
        of cancer. Anecdotal clinical evidence has shown regression of tumours with ingestion of such
        medicinal cannabis. A randomized controlled trial in Glioblastoma Multiforme, a kind of brain
        tumour, shows improvement in disease free survival when temozolamide was combined with
        Cannabis spray called Sativex.
  
        However, because of lack of systematic, large volume studies, the evidence is slow to emerge.
        We have previously seen changes related to NF-kb (inflammation) and AP1 (acute
        hypoxia/stress) pathway genes within the tumour tissue as assessed by transcriptomic analysis
        (Yet unpublished data). There is laboratory evidence to suggest that the changes induced in
        the AP1 pathway during surgery can be ameliorated by cannabis treatment. We intend to explore
        this anticancer potential of C sativa herbal preparation in the pre-operative setting in
        breast and head and neck cancer patients. Hence, we are proposing a phase 1 study to assess
        the pharmacokinetic availability and safety and tolerability profile of one such ayurvedic
        preparation which contains 5 mg THC:CBD 1:1 preparation. Other than the PK profile, we will
        also be studying its effect on gene expression profiling of the breast and head neck oral
        cavity squamous cell carcinoma tissue.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: To determine the maximum tolerated dose (MTD). First 3 patients will receive the study preparation once a day at 9 am (+/- 60 min) (i.e 5 mg of CBD and 5 mg of THC in a 400 mg capsule). Subsequent cohorts will be administered doses of 10 (10 mg of THC and CBD each), 20 (20+20) and 30 (30+30) mg in a classical 3+3 dose escalation study. Briefly, 3 patients will be enrolled at dose level. Dose escalation to the next dose level will continue as long no DLT is observed in 3 patients (the incidence of DLT is ≤ 1/6) In any cohort, if 1/3 patients develop DLT, then 3 more patients will be added at that dose. The dose level at which more than 1/6 patients develop DLT will be considered the MTD and no further escalation will be done beyond the MTD. One dose level below the MTD will be considered for future trials. If MTD is not achieved, the highest dose (30+30) will be considered for future trials. If toxicity is seen at 30 mg, then de-escalation to 25 mg may be considered.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: To establish safe dose of oral cannabis preparation
  time frame: From day 1 of IP dosing till 28 days .
  description: Number of participants with treatment-related adverse events with respect to cardiovascular, central nervous system and psychotropic of cannabis as assessed by CTCAE v4.0
  measure: Pharmacokinetic profiling
  time frame: 1.Pre operative day 1 to 5 - one each day before cannabinoid dosing, after dosing 30 minutes, 1 hour, 2 hour and 8 hour. 2. On day of surgery - Before and after the surgery 3. Post operative day 1 , day 2, day 3 and day 14
  description: Blood samples collected during the administration of the IP for 5 days and up to 72 hours after surgery.
  measure: Biomarker analysis- Transcitpomics
  time frame: A baseline pre-cannabis tumor tissue sample will be collected before starting IP(day 0). Further blood and tumor as well as adjacent normal tissue samples will be collected during surgery (day6).
  description: Tumor and normal tissue samples.
  arm group label: Cannabis
  arm group type: Experimental
  description: Cannabis capsules containing 5 mg of THC and CBD each or 2.5 mg of THC and CBD each.
  intervention type: Drug
  intervention name: Cannabis capsules
  description: Cannabis capsules containing 5 mg of THC and CBD each or 2.5 mg of THC and CBD each.
  arm group label: Cannabis
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Rajendra A Badwe, MS
  role: Principal Investigator
  affiliation: Director, Tata Memorial Centre
  facility: 
  facility: 
  country: India
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  PMID: 21592732
  responsible party type: Principal Investigator
  investigator affiliation: Tata Memorial Hospital
  investigator full name: Dr Rajendra A. Badwe
  investigator title: Doctor
  mesh term: Mouth Neoplasms
  sharing ipd: No