<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/NCT01685190</url>
  </required_header>
  <id_info>
    <org_study_id>ICR-CTSU/2010/10025</org_study_id>
    <secondary_id>CRUK/10/022</secondary_id>
    <secondary_id>ISRCTN48709247</secondary_id>
    <nct_id>NCT01685190</nct_id>
  </id_info>
  <brief_title>A Study of Prostate and pelvIs Versus prOsTate Alone Treatment for Locally Advanced Prostate Cancer</brief_title>
  <acronym>PIVOTAL</acronym>
  <official_title>A Randomised Phase II Trial of Prostate and pelvIs Versus prOsTate Alone Treatment for Locally Advanced Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Cancer Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cancer Research UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institute of Cancer Research, United Kingdom</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prostate cancer is the most common male cancer in the UK with 35,000 cases diagnosed&#xD;
      annually. 35% of these are locally advanced disease. These patients have a high chance of&#xD;
      pelvic lymph node involvement and have relatively poor prostate cancer survival rates of&#xD;
      22.5% at 10 years.&#xD;
&#xD;
      One of the standard treatments for these patients is radiotherapy to the prostate. PIVOTAL is&#xD;
      a multi-centre phase II non-comparative randomised feasibility trial, in which patients with&#xD;
      a high chance of pelvic lymph node involvement are randomised between prostate radiotherapy&#xD;
      alone and prostate + pelvic radiotherapy.&#xD;
&#xD;
      Both groups will receive radiotherapy called Intensity Modulated Radiation Therapy (IMRT).&#xD;
      This is a relatively new method of shaping radiotherapy treatment beams which allows the&#xD;
      tumour to be treated more precisely, whilst avoiding more of the surrounding normal, healthy&#xD;
      tissues (particularly the rectum, bladder and bowel). Using IMRT, it is possible to deliver&#xD;
      higher doses of radiotherapy to the pelvis than with previous radiotherapy methods - this has&#xD;
      been tested in a single hospital, single group setting and levels of side effects (toxicity)&#xD;
      were acceptable.&#xD;
&#xD;
      PIVOTAL aims to find out whether toxicity levels at 18 weeks from the start of radiotherapy&#xD;
      remain acceptable when treatment is given in multiple cancer centres across the UK. It is&#xD;
      randomised to ensure unbiased collection of acute toxicity data and to provide information on&#xD;
      patients' willingness to participate in a randomised study. Should the phase II study be&#xD;
      successful, the investigators would develop a phase III trial to compare treatment&#xD;
      effectiveness (disease control).&#xD;
&#xD;
      Patients who enter PIVOTAL will be followed up for two years from the start of radiotherapy&#xD;
      and data relating to toxicity will be collected. They will also be asked to complete patient&#xD;
      related symptoms questionnaires. Data related to disease recurrence will then be collected&#xD;
      annually from patients' standard hospital visits.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>June 2011</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2013</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Acute lower GI RTOG toxicity at week 18 of follow-up.</measure>
    <time_frame>18 weeks post treatment</time_frame>
    <description>Proportion of patients with acute GI RTOG grade ≥2 toxicity at week 18 from start of radiotherapy calculated as the number of patients with grade ≥2 toxicity at week 18 over the number of evaluable at week 18.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ability to deliver 60Gy in 37 fractions to the pelvis using the varying radiotherapy planning techniques and delivery systems at the participating centres.</measure>
    <time_frame>2 yr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late (1 and 2 year) toxicity</measure>
    <time_frame>2 yr</time_frame>
    <description>Measured using RTOG toxicity scale and CTCAE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Reported Outcomes</measure>
    <time_frame>2 yr</time_frame>
    <description>Participants are requested to complete questionnaires to record the impact of the treatments on bowel and bladder function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical progression free survival</measure>
    <time_frame>10 yr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to local progression</measure>
    <time_frame>10 yr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to distant metastases</measure>
    <time_frame>10 yr</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>10 yr</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">124</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Prostate Alone IMRT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive standard prostate Intensity Modulated Radiotherapy (IMRT) of 74Gy in 37 fractions delivered over 7.5 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prostate &amp; Pelvis IMRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive prostate and pelvis IMRT with a dose of 74Gy in 37 fractions delivered over 7.5 weeks to the prostate and 60Gy in 37 fractions delivered over 7.5weeks to the pelvis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Prostate alone IMRT</intervention_name>
    <description>Participants will receive standard prostate IMRT of 74Gy in 37 fractions delivered over 7.5 weeks.</description>
    <arm_group_label>Prostate Alone IMRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Prostate and pelvis IMRT</intervention_name>
    <description>Participants will receive prostate and pelvis IMRT with a dose of 74Gy in 37 fractions delivered over 7.5 weeks to the prostate and 60Gy in 37 fractions delivered over 7.5weeks to the pelvis.</description>
    <arm_group_label>Prostate &amp; Pelvis IMRT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed, non-metastatic adenocarcinoma of the prostate, previously&#xD;
             untreated (other than by neoadjuvant hormonal treatment)&#xD;
&#xD;
          2. National Collaborative Cancer Network locally advanced disease (T3b± or T4)43 or:&#xD;
&#xD;
             • Estimated risk of pelvic lymph node involvement ≥30% * and either:&#xD;
&#xD;
               -  Gleason 9 or 10 or&#xD;
&#xD;
               -  Gleason 8 and one other high risk feature (T3± disease or PSA &gt;20) or&#xD;
&#xD;
               -  Gleason 7 and 2 high risk features (T3± disease and PSA ≥30)&#xD;
&#xD;
          3. WHO performance status 0 or 1&#xD;
&#xD;
          4. Normal blood count (Hb &gt; 11g/dl, WBC &gt;4000/mm3, platelets &gt;100,000/mm3)&#xD;
&#xD;
          5. LHRH analogue therapy for 6-9 months duration prior to proposed radiotherapy treatment&#xD;
             and PSA &lt; 4ng/ml prior to randomisation.&#xD;
&#xD;
          6. Age ≥ 18 years&#xD;
&#xD;
          7. Patients must be prepared to attend follow up. All patients participating in the&#xD;
             Patient Reported Outcomes (PRO) Study must have adequate cognitive ability to complete&#xD;
             the PRO questionnaires.&#xD;
&#xD;
          8. Written informed consent&#xD;
&#xD;
               -  T3a disease should be demonstrated convincingly, either clinically or by MRI. T3b&#xD;
                  disease (seminal vesicle involvement) must be convincingly demonstrated on MR.&#xD;
&#xD;
                    -  Risk of pelvic lymph node involvement = (Gleason score - 6) x 10 + 2/3 PSA&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Prior pelvic radiotherapy&#xD;
&#xD;
          2. Prior major pelvic surgery (e.g. colectomy, colostomy, cystectomy, prostatectomy)*&#xD;
&#xD;
          3. Radiologically suspicious (short axis diameter ≥1.0cm unless biopsied and negative) or&#xD;
             pathologically confirmed lymph node involvement&#xD;
&#xD;
          4. Life expectancy &lt; 5 years&#xD;
&#xD;
          5. Castrate resistant prostate cancer (rising PSA after LHRHa and anti-androgen)&#xD;
&#xD;
          6. Previous active malignancy within the last 5 years other than basal cell carcinoma&#xD;
&#xD;
          7. Co-morbid conditions likely to impact on the decision to treat with radiotherapy (e.g.&#xD;
             previous inflammatory bowel disease, previous colo-rectal surgery, significant bladder&#xD;
             instability or urinary incontinence)&#xD;
&#xD;
          8. Bilateral hip prosthesis or fixation which would interfere with standard radiation&#xD;
             beam configuration&#xD;
&#xD;
               -  Patients who have undergone minor pelvic surgery will be eligible (eg&#xD;
                  appendicectomy, trans urethral resection of prostate (TURP), exploratory&#xD;
                  laparoscopy, haemorrhoidectomy, inguinal/femoral hernia repair)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Prof. David Dearnaley</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Cancer Research/RMHNHSFT</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Queen Elizabeth</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Addenbrooke's Hospital</name>
      <address>
        <city>Cambridge</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Velindre Hospital</name>
      <address>
        <city>Cardiff</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ipswich</name>
      <address>
        <city>Ipswich</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clatterbridge Centre for Oncology</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden NHSFT</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Freeman Hospital</name>
      <address>
        <city>Newcastle</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Harris VA, Staffurth J, Naismith O, Esmail A, Gulliford S, Khoo V, Lewis R, Littler J, McNair H, Sadoyze A, Scrase C, Sohaib A, Syndikus I, Zarkar A, Hall E, Dearnaley D; PIVOTAL Trialists. Consensus Guidelines and Contouring Atlas for Pelvic Node Delineation in Prostate and Pelvic Node Intensity Modulated Radiation Therapy. Int J Radiat Oncol Biol Phys. 2015 Jul 15;92(4):874-83. doi: 10.1016/j.ijrobp.2015.03.021. Epub 2015 Mar 30.</citation>
    <PMID>26104940</PMID>
  </reference>
  <results_reference>
    <citation>Dearnaley D, Griffin CL, Lewis R, Mayles P, Mayles H, Naismith OF, Harris V, Scrase CD, Staffurth J, Syndikus I, Zarkar A, Ford DR, Rimmer YL, Horan G, Khoo V, Frew J, Venkitaraman R, Hall E. Toxicity and Patient-Reported Outcomes of a Phase 2 Randomized Trial of Prostate and Pelvic Lymph Node Versus Prostate only Radiotherapy in Advanced Localised Prostate Cancer (PIVOTAL). Int J Radiat Oncol Biol Phys. 2019 Mar 1;103(3):605-617. doi: 10.1016/j.ijrobp.2018.10.003. Epub 2018 Dec 6.</citation>
    <PMID>30528653</PMID>
  </results_reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>October 26, 2011</study_first_submitted>
  <study_first_submitted_qc>September 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 14, 2012</study_first_posted>
  <last_update_submitted>January 2, 2019</last_update_submitted>
  <last_update_submitted_qc>January 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 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>Prostatic Neoplasms</mesh_term>
  </condition_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/NCT01685190
org study id: ICR-CTSU/2010/10025
secondary id: CRUK/10/022
secondary id: ISRCTN48709247
nct id: NCT01685190
lead sponsor: 
collaborator: 
has dmc: Yes
Prostate cancer is the most common male cancer in the UK with 35,000 cases diagnosed
      annually. 35% of these are locally advanced disease. These patients have a high chance of
      pelvic lymph node involvement and have relatively poor prostate cancer survival rates of
      22.5% at 10 years.

      One of the standard treatments for these patients is radiotherapy to the prostate. PIVOTAL is
      a multi-centre phase II non-comparative randomised feasibility trial, in which patients with
      a high chance of pelvic lymph node involvement are randomised between prostate radiotherapy
      alone and prostate + pelvic radiotherapy.

      Both groups will receive radiotherapy called Intensity Modulated Radiation Therapy (IMRT).
      This is a relatively new method of shaping radiotherapy treatment beams which allows the
      tumour to be treated more precisely, whilst avoiding more of the surrounding normal, healthy
      tissues (particularly the rectum, bladder and bowel). Using IMRT, it is possible to deliver
      higher doses of radiotherapy to the pelvis than with previous radiotherapy methods - this has
      been tested in a single hospital, single group setting and levels of side effects (toxicity)
      were acceptable.

      PIVOTAL aims to find out whether toxicity levels at 18 weeks from the start of radiotherapy
      remain acceptable when treatment is given in multiple cancer centres across the UK. It is
      randomised to ensure unbiased collection of acute toxicity data and to provide information on
      patients' willingness to participate in a randomised study. Should the phase II study be
      successful, the investigators would develop a phase III trial to compare treatment
      effectiveness (disease control).

      Patients who enter PIVOTAL will be followed up for two years from the start of radiotherapy
      and data relating to toxicity will be collected. They will also be asked to complete patient
      related symptoms questionnaires. Data related to disease recurrence will then be collected
      annually from patients' standard hospital visits.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Acute lower GI RTOG toxicity at week 18 of follow-up.
time frame: 18 weeks post treatment
description: Proportion of patients with acute GI RTOG grade ≥2 toxicity at week 18 from start of radiotherapy calculated as the number of patients with grade ≥2 toxicity at week 18 over the number of evaluable at week 18.
measure: Ability to deliver 60Gy in 37 fractions to the pelvis using the varying radiotherapy planning techniques and delivery systems at the participating centres.
time frame: 2 yr
measure: Late (1 and 2 year) toxicity
time frame: 2 yr
description: Measured using RTOG toxicity scale and CTCAE
measure: Patient Reported Outcomes
time frame: 2 yr
description: Participants are requested to complete questionnaires to record the impact of the treatments on bowel and bladder function.
measure: Biochemical progression free survival
time frame: 10 yr
measure: Time to local progression
time frame: 10 yr
measure: Time to distant metastases
time frame: 10 yr
measure: Overall survival
time frame: 10 yr
arm group label: Prostate Alone IMRT
arm group type: Active Comparator
description: Participants will receive standard prostate Intensity Modulated Radiotherapy (IMRT) of 74Gy in 37 fractions delivered over 7.5 weeks.
arm group label: Prostate & Pelvis IMRT
arm group type: Experimental
description: Participants will receive prostate and pelvis IMRT with a dose of 74Gy in 37 fractions delivered over 7.5 weeks to the prostate and 60Gy in 37 fractions delivered over 7.5weeks to the pelvis.
intervention type: Radiation
intervention name: Prostate alone IMRT
description: Participants will receive standard prostate IMRT of 74Gy in 37 fractions delivered over 7.5 weeks.
arm group label: Prostate Alone IMRT
intervention type: Radiation
intervention name: Prostate and pelvis IMRT
description: Participants will receive prostate and pelvis IMRT with a dose of 74Gy in 37 fractions delivered over 7.5 weeks to the prostate and 60Gy in 37 fractions delivered over 7.5weeks to the pelvis.
arm group label: Prostate & Pelvis IMRT
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Prof. David Dearnaley
role: Principal Investigator
affiliation: Institute of Cancer Research/RMHNHSFT
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United Kingdom
citation: Harris VA, Staffurth J, Naismith O, Esmail A, Gulliford S, Khoo V, Lewis R, Littler J, McNair H, Sadoyze A, Scrase C, Sohaib A, Syndikus I, Zarkar A, Hall E, Dearnaley D; PIVOTAL Trialists. Consensus Guidelines and Contouring Atlas for Pelvic Node Delineation in Prostate and Pelvic Node Intensity Modulated Radiation Therapy. Int J Radiat Oncol Biol Phys. 2015 Jul 15;92(4):874-83. doi: 10.1016/j.ijrobp.2015.03.021. Epub 2015 Mar 30.
PMID: 26104940
citation: Dearnaley D, Griffin CL, Lewis R, Mayles P, Mayles H, Naismith OF, Harris V, Scrase CD, Staffurth J, Syndikus I, Zarkar A, Ford DR, Rimmer YL, Horan G, Khoo V, Frew J, Venkitaraman R, Hall E. Toxicity and Patient-Reported Outcomes of a Phase 2 Randomized Trial of Prostate and Pelvic Lymph Node Versus Prostate only Radiotherapy in Advanced Localised Prostate Cancer (PIVOTAL). Int J Radiat Oncol Biol Phys. 2019 Mar 1;103(3):605-617. doi: 10.1016/j.ijrobp.2018.10.003. Epub 2018 Dec 6.
PMID: 30528653
responsible party type: Sponsor
mesh term: Prostatic Neoplasms