<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/NCT02230800</url>
  </required_header>
  <id_info>
    <org_study_id>CCR3894</org_study_id>
    <nct_id>NCT02230800</nct_id>
  </id_info>
  <brief_title>PPALM-Palm Oil and Pentoxifylline Against Late Morbidity</brief_title>
  <acronym>PPALM</acronym>
  <official_title>Randomised Double-blind Placebo Controlled Phase II Trial of Tocovid SupraBio in Combination With Pentoxifylline (PTX) in Patients Suffering Long-term Adverse Effects of Radiotherapy for Pelvic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal Marsden NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Malaysia Palm Oil Board</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Royal Marsden NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Side effects are common after treatment with radiotherapy for tumours in the pelvis and can&#xD;
      affect the way the bowel and urinary system work as well as causing sexual difficulties, skin&#xD;
      damage and bone problems. Problems in the bowel, bladder, sexual organs and skin mostly&#xD;
      result from thickening of the tissues in response to radiotherapy, a process called&#xD;
      &quot;fibrosis&quot;. Fibrosis often worsens over time.&#xD;
&#xD;
      There has been progress in treating bowel symptoms which usually are the worst problem after&#xD;
      radiotherapy. However, even after receiving the best possible treatments, while many patients&#xD;
      are better, they are often not cured of all their difficult problems.&#xD;
&#xD;
      For some years, it has been hypothesised that if fibrosis could be treated then symptoms&#xD;
      would improve. Recent research in laboratory animals has suggested that an effective&#xD;
      treatment for radiation-induced fibrosis is combination therapy with a drug called&#xD;
      Pentoxifylline together with a nutritional supplement containing gamma-tocotrienol (Tocovid&#xD;
      SupraBio), a substance derived from palm oil. Both of these agents are simple to take and&#xD;
      side effects are rare.&#xD;
&#xD;
      This study will recruit volunteers who continue to have difficult side effects after previous&#xD;
      radiotherapy to the pelvis despite receiving the best treatments available from a unique&#xD;
      clinic at The Royal Marsden which has pioneered treatment for bowel problems after&#xD;
      radiotherapy. Two out of every three volunteers who take part, will be randomly assigned to&#xD;
      treatment with Pentoxifylline and Tocovid SupraBio, while one out of three will receive dummy&#xD;
      pills. Neither the patients nor the staff assessing them will know which treatment they have&#xD;
      been given. Volunteers take the active treatments or dummy tablets for a year and will be&#xD;
      assessed regularly while on treatment and for a year afterwards. This study will show whether&#xD;
      active treatment is more effective than dummy pills in improving the symptoms caused by&#xD;
      radiation-induced fibrosis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 25, 2014</start_date>
  <completion_date type="Actual">December 20, 2019</completion_date>
  <primary_completion_date type="Actual">December 20, 2019</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change at 12 months in the bowel disease subset of the Modified IBDQ Quality of Life questionnaire.</measure>
    <time_frame>Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 &amp; 24 months post-treatment.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change at 12 months in rectal IBDQ bleeding score between the two groups in those patients presenting with grade 2, 3 or 4 bleeding.</measure>
    <time_frame>Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 &amp; 24 months post-treatment.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change at 12 months in IBDQ faecal incontinence score between the two groups in those patients presenting with grade 1 or greater incontinence.</measure>
    <time_frame>Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 &amp; 24 months post-treatment.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of items graded as marked or severe (grade 3 or 4).</measure>
    <time_frame>Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 &amp; 24 months post-treatment.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physician assessment of rectal dysfunction based on the modified CTCAE Version 4 grading.</measure>
    <time_frame>Endpoint will be assessed pre-treatment and 6, 12 &amp; 24 months post-treatment.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient self-assessments: QLQ-C30 and CR29 and the Gastrointestinal Symptom Rating Scale.</measure>
    <time_frame>Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 &amp; 24 months post-treatment.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Photographic assessment of rectal mucosa.</measure>
    <time_frame>Endpoint will be assessed pre-treatment and 12 &amp; 24 months post-treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum fibrosis marker levels.</measure>
    <time_frame>Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 &amp; 24 months post-treatment.</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Translational endpoint: Rectal biopsies (optional)</measure>
    <time_frame>Endpoint will be assessed pre-treatment and 12 &amp; 24 months post-treatment.</time_frame>
    <description>Tissue samples will be banked until after the final analysis of the trial, when funding will be sought to identify molecular and cellular correlates of therapeutic response in the event of a statistically significant benefit for Tocovid SupraBio/ PTX combination.</description>
  </other_outcome>
  <other_outcome>
    <measure>Translational endpoint: Blood samples</measure>
    <time_frame>Endpoint will be assessed pre-treatment and 12 &amp; 24 months post-treatment.</time_frame>
    <description>Development of novel markers of fibrosis.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Long-term Adverse Effects of Radiotherapy for Pelvic Cancer</condition>
  <arm_group>
    <arm_group_label>Tocovid SupraBio plus pentoxifylline (PTX)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tocovid SupraBio* 200mg po bd plus pentoxifylline (PTX) 400mg po bd for 12 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Matching placebos</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebos bd for 12 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocovid SupraBio plus pentoxifylline</intervention_name>
    <arm_group_label>Tocovid SupraBio plus pentoxifylline (PTX)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Matching placebos</intervention_name>
    <arm_group_label>Matching placebos</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria -&#xD;
&#xD;
          -  Age over 18 years.&#xD;
&#xD;
          -  Past history of a malignant pelvic neoplasm (T1-4 N0-2 M0) of the rectum, prostate,&#xD;
             testis, bladder, uterine cervix, uterus, vagina, vulva, anal canal or ovary.&#xD;
&#xD;
          -  A minimum 12 months follow-up post-radiotherapy (24 months for patients with past&#xD;
             history of stage T4 and/or N2 disease).&#xD;
&#xD;
          -  A maximum 7 years post-radiotherapy&#xD;
&#xD;
          -  No evidence of cancer recurrence.&#xD;
&#xD;
          -  Gastrointestinal symptoms attributable to prior radiotherapy: grade 2 or higher in any&#xD;
             CTCAE Version 4 category, or grade 1 with difficult intermittent symptoms.&#xD;
&#xD;
          -  Symptoms are not relieved by appropriate life-style advice and medication over a&#xD;
             3-month period.&#xD;
&#xD;
          -  Physical and psychological fitness for Tocovid SupraBio+PTX therapy.&#xD;
&#xD;
          -  Written informed consent and availability for follow up.&#xD;
&#xD;
          -  Willingness to keep to a specified level of dietary fat intake during the study.&#xD;
&#xD;
        Exclusion Criteria -&#xD;
&#xD;
          -  Surgery for rectal cancer.&#xD;
&#xD;
          -  Contra-indication or other inability to undergo magnetic resonance imaging, if&#xD;
             required to rule out malignancy.&#xD;
&#xD;
          -  Dietary supplementation containing alpha-tocopherol above a daily dose of 30mg at any&#xD;
             time during the last three months.&#xD;
&#xD;
          -  Medication with pentoxifylline at any time since radiotherapy.&#xD;
&#xD;
          -  Pregnancy or breast feeding.&#xD;
&#xD;
          -  Ischaemic heart disease, uncontrolled hypertension, hypotension, acute myocardial&#xD;
             infarction, cerebral haemorrhage, retinal haemorrhage, renal failure, liver failure&#xD;
             and medication with insulin, ketorolac or vitamin K.&#xD;
&#xD;
          -  Allergy to soya.&#xD;
&#xD;
          -  Known hypersensitivity to the active constituent, pentoxifylline other methyl&#xD;
             xanthines or any of the excipients', as per SmPC for pentoxifylline.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexandra Taylor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Marsden NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Royal Marsden NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <last_update_submitted>December 20, 2019</last_update_submitted>
  <last_update_submitted_qc>December 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 23, 2019</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>Pelvic Neoplasms</mesh_term>
    <mesh_term>Long Term Adverse Effects</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tocovid</mesh_term>
    <mesh_term>Pentoxifylline</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/NCT02230800
org study id: CCR3894
nct id: NCT02230800
lead sponsor: 
collaborator: 
has dmc: No
Side effects are common after treatment with radiotherapy for tumours in the pelvis and can
      affect the way the bowel and urinary system work as well as causing sexual difficulties, skin
      damage and bone problems. Problems in the bowel, bladder, sexual organs and skin mostly
      result from thickening of the tissues in response to radiotherapy, a process called
      "fibrosis". Fibrosis often worsens over time.

      There has been progress in treating bowel symptoms which usually are the worst problem after
      radiotherapy. However, even after receiving the best possible treatments, while many patients
      are better, they are often not cured of all their difficult problems.

      For some years, it has been hypothesised that if fibrosis could be treated then symptoms
      would improve. Recent research in laboratory animals has suggested that an effective
      treatment for radiation-induced fibrosis is combination therapy with a drug called
      Pentoxifylline together with a nutritional supplement containing gamma-tocotrienol (Tocovid
      SupraBio), a substance derived from palm oil. Both of these agents are simple to take and
      side effects are rare.

      This study will recruit volunteers who continue to have difficult side effects after previous
      radiotherapy to the pelvis despite receiving the best treatments available from a unique
      clinic at The Royal Marsden which has pioneered treatment for bowel problems after
      radiotherapy. Two out of every three volunteers who take part, will be randomly assigned to
      treatment with Pentoxifylline and Tocovid SupraBio, while one out of three will receive dummy
      pills. Neither the patients nor the staff assessing them will know which treatment they have
      been given. Volunteers take the active treatments or dummy tablets for a year and will be
      assessed regularly while on treatment and for a year afterwards. This study will show whether
      active treatment is more effective than dummy pills in improving the symptoms caused by
      radiation-induced fibrosis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change at 12 months in the bowel disease subset of the Modified IBDQ Quality of Life questionnaire.
time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
measure: Change at 12 months in rectal IBDQ bleeding score between the two groups in those patients presenting with grade 2, 3 or 4 bleeding.
time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
measure: Change at 12 months in IBDQ faecal incontinence score between the two groups in those patients presenting with grade 1 or greater incontinence.
time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
measure: Proportion of items graded as marked or severe (grade 3 or 4).
time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
measure: Physician assessment of rectal dysfunction based on the modified CTCAE Version 4 grading.
time frame: Endpoint will be assessed pre-treatment and 6, 12 & 24 months post-treatment.
measure: Patient self-assessments: QLQ-C30 and CR29 and the Gastrointestinal Symptom Rating Scale.
time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
measure: Photographic assessment of rectal mucosa.
time frame: Endpoint will be assessed pre-treatment and 12 & 24 months post-treatment
measure: Serum fibrosis marker levels.
time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
measure: Translational endpoint: Rectal biopsies (optional)
time frame: Endpoint will be assessed pre-treatment and 12 & 24 months post-treatment.
description: Tissue samples will be banked until after the final analysis of the trial, when funding will be sought to identify molecular and cellular correlates of therapeutic response in the event of a statistically significant benefit for Tocovid SupraBio/ PTX combination.
measure: Translational endpoint: Blood samples
time frame: Endpoint will be assessed pre-treatment and 12 & 24 months post-treatment.
description: Development of novel markers of fibrosis.
arm group label: Tocovid SupraBio plus pentoxifylline (PTX)
arm group type: Experimental
description: Tocovid SupraBio* 200mg po bd plus pentoxifylline (PTX) 400mg po bd for 12 months.
arm group label: Matching placebos
arm group type: Placebo Comparator
description: Matching placebos bd for 12 months.
intervention type: Drug
intervention name: Tocovid SupraBio plus pentoxifylline
arm group label: Tocovid SupraBio plus pentoxifylline (PTX)
intervention type: Drug
intervention name: Matching placebos
arm group label: Matching placebos
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alexandra Taylor
role: Principal Investigator
affiliation: Royal Marsden NHS Foundation Trust
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Pelvic Neoplasms
mesh term: Long Term Adverse Effects
mesh term: Tocovid
mesh term: Pentoxifylline