<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/NCT03763253</url>
  </required_header>
  <id_info>
    <org_study_id>18HH4804</org_study_id>
    <nct_id>NCT03763253</nct_id>
  </id_info>
  <brief_title>Additional Treatments to the Local Tumour for Metastatic Prostate Cancer: Assessment of Novel Treatment Algorithms</brief_title>
  <acronym>IP2-ATLANTA</acronym>
  <official_title>Local Cytoreductive Treatments for Men With Newly Diagnosed Metastatic Prostate Cancer in Addition to Standard of Care Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Wellcome Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Imperial College London</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>
      Local cytoreductive treatments for men with newly diagnosed metastatic prostate cancer in&#xD;
      addition to standard of care treatment&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TITLE: Additional Treatments to the Local tumour for metastatic prostate cancer: Assessment&#xD;
      of Novel Treatment Algorithms (ATLANTA)&#xD;
&#xD;
      OBJECTIVES: To determine whether the addition of local treatment to the prostate (minimally&#xD;
      invasive therapy or radical therapy [prostatectomy or radiotherapy]), including selective&#xD;
      metastases-directed therapy, improves oncological outcomes in men receiving standard of care&#xD;
      treatment for newly diagnosed metastatic prostate cancer&#xD;
&#xD;
      PHASE: Phase II Randomised Control Trial (RCT) incorporating an internal pilot&#xD;
&#xD;
      DESIGN: Three-arm unblinded randomised controlled trial using a positive control&#xD;
&#xD;
      SAMPLE SIZE: 399&#xD;
&#xD;
      POPULATION: Men who are willing to undergo local therapy to the prostate and selective&#xD;
      metastases-directed therapy for metastatic prostate cancer in addition to standard care&#xD;
      systemic treatment.&#xD;
&#xD;
      STUDY HYPOTHESIS: We hypothesise that men with metastatic disease who undergo treatment of&#xD;
      the local tumour in the form of either radical therapy (prostatectomy or radiotherapy) or&#xD;
      minimally invasive ablative therapy (MIAT), combined with metastases directly therapy, will&#xD;
      have improved survival compared to those who receive standard of treatment alone. We will be&#xD;
      investigating this newly evolving treatment paradigm in a formal randomised control trial&#xD;
      (RCT).&#xD;
&#xD;
      TREATMENT/MAIN STUDY PROCEDURES: (including treatment duration and follow-up) Our pragmatic&#xD;
      design ensures all eligible patients can be approached and randomised as there is no&#xD;
      requirement for fitness to undergo RP. The design also incorporates the latest approach for&#xD;
      standard of care as well as management of lymph nodes.&#xD;
&#xD;
      Arm 1*: Standard of Care (SOC) treatment as determined by treating physician (positive&#xD;
      control) (androgen deprivation with or without Docetaxel chemotherapy or other systemic/local&#xD;
      directed standard of care treatment including but not limited to Abiraterone or&#xD;
      Enzalutamide). Radiotherapy in this arm defined as palliative/cytoreductive in high volume&#xD;
      metastases or to mirror STAMPEDE local radiotherapy arm in low volume metastases.&#xD;
&#xD;
      Arm 2**: Minimally Invasive Ablative Therapy (MIAT) to local tumour / prostate in addition to&#xD;
      SOC systemic treatment. Predominantly cryotherapy but based on disease characteristics, HIFU&#xD;
      also. Metastases directed therapy declared prior to randomisation.&#xD;
&#xD;
      Arm 3**: Radical therapy (Prostatectomy or External beam radiotherapy [60Gy x 20 or 74Gy + in&#xD;
      32-37 weeks]) in addition to SOC systemic treatment. Modality based on physician and patient&#xD;
      preference and patient co-morbidities. Metastases directed therapy declared prior to&#xD;
      randomisation.&#xD;
&#xD;
      FOLLOW-UP DURATION: Until progression or minimum 2-years or maximum 4 years whichever is&#xD;
      first (or 6 months for the Pilot if the trial does not progress to Phase II).&#xD;
&#xD;
      Prior to enrolment all patients must undergo Standard of Care (SOC) staging investigations&#xD;
      for localised and metastatic disease and will need to have histologically proven local&#xD;
      disease within the prostate. There will be no restriction on the type of biopsy used for&#xD;
      diagnosis.&#xD;
&#xD;
      *ADT but not chemotherapy may be initiated prior to recruitment.The decision as to which SOC&#xD;
      systemic therapy regimen will be used is by the treating clinician and/or clinical team (to&#xD;
      be declared upfront prior to randomisation). If radiotherapy is planned for local disease in&#xD;
      some cases in the SOC arm then this will be declared upfront prior to randomisation by the&#xD;
      treating physician. Similarly, if lymph node radiotherapy is to be advocated then this is to&#xD;
      be declared upfront prior to randomisation by the treating physician and can be applied to&#xD;
      any one of the three arms. Randomisation into a treatment arm would occur at the time of&#xD;
      recruitment which would be within 3 months of starting SOC systemic therapy.&#xD;
&#xD;
      Extra blood and urine samples will be identified using a special study number assigned to&#xD;
      each patient, in such a way that the scientists analysing them will not be able to find out&#xD;
      patients identity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 10, 2019</start_date>
  <completion_date type="Anticipated">January 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2026</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>Factorial Assignment</intervention_model>
    <intervention_model_description>Three-arm unblinded randomised controlled trial using a positive control</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Prostate cancer on post-standard of care prostate biopsy.</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of patients with complete pathological response, measured on post SOC (systemic therapy) prostate biopsies (Internal Pilot).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety (Adverse Events)</measure>
    <time_frame>2-4 years (continuous)</time_frame>
    <description>Safety (Adverse Events), measured using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, Grade 1-5.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>2-4 years</time_frame>
    <description>Progression-free survival (PFS), measured as a composite outcome of Biochemical failure (PSA progression value) or Local progression or Lymph node progression or Bone metastases progression (new sites) or Progression or development of new distant metastases, defined as lymph nodes outside the pelvis, bone or organ involvement or Skeletal-related events confirmed as progression as in the Systemic Therapy in Advancing Or Metastatic Prostate Cancer: Evaluation Of Drug Efficacy (STAMPEDE) RCT).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Urinary side effects</measure>
    <time_frame>Baseline, week 26, 52, then at 24 months.</time_frame>
    <description>Urinary side effects, measured using the IPSS questionnaire, Score 0-35.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sexual side effects</measure>
    <time_frame>Baseline, week 26, 52, then at 24 months.</time_frame>
    <description>Sexual side effects, measured using the IIEF15 questionnaire, Score 0-75.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rectal side effects</measure>
    <time_frame>Baseline, week 26, 52, then at 24 months.</time_frame>
    <description>Rectal side effects, measured using the EPIC bowel and bladder questionnaire, Score 14-113.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression (Biochemical / Radiological / Clinical)</measure>
    <time_frame>Baseline, week 12, 26, 34, 52 then every every 24 weeks for remaining years 2 to 4 and Imaging tests at baseline and if progression is suspected by a clinician</time_frame>
    <description>Progression on PSA and imaging and impact of clinical features on progression, measured using PSA blood tests</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality-of-life</measure>
    <time_frame>Baseline, week 26, 52, then at 24 months.</time_frame>
    <description>Health-related quality-of-life, measured using EuroQol (EQ-5D-5L) questionnaire, Score 0-100.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">399</enrollment>
  <condition>Prostate Cancer</condition>
  <condition>Metastatic Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Control Arm: Standard of Care (SOC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of Care (SOC) treatment as determined by treating physician (positive control) (androgen deprivation with or without docetaxel chemotherapy or other systemic standard of care treatment including but not limited to Abiraterone or Enzalutamide).&#xD;
Radiotherapy to the prostate in this arm is defined as cytoreductive (for symptom control) in high volume (&gt;/=4) metastases or to mirror current accepted local radiotherapy dose regimens for men with low volume metastases (&lt;4 metastases).&#xD;
Metastases directed therapy will not be permitted in the control arm. Palliative radiotherapy for symptom control or for prevention of fracture will be permitted as standard clinical practice.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention Arm 1: Minimally Invasive Ablative Therapy (MIAT)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>MIAT to prostate in form of cryotherapy or high intensity focused ultrasound (HIFU), in addition to SOC systemic treatment. No local prostate radiotherapy will be given as part of this intervention. Radiotherapy can be given subsequently for palliative reasons.&#xD;
Metastatic directed therapy will be available for use in this arm (if declared at randomisation).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention Arm 2: Radical Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Radical therapy in form of prostatectomy (any approach) or external beam radiotherapy (radical dose) in addition to SOC systemic treatment. Modality based on physician and patient preference and patient co-morbidities.&#xD;
For patients undergoing radical prostatectomy no local prostate radiotherapy will be given as part of the intervention. Radiotherapy can be given subsequently for palliative reasons.&#xD;
Radical radiotherapy doses in this arm will be higher than SOC.&#xD;
Metastatic directed therapy will be available for use in this arm (if declared at randomisation).</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Androgen deprivation with or without docetaxel chemotherapy, Abiraterone, Enzalutamide or any other proven agent) treatment as determined by treating physician (positive control).</description>
    <arm_group_label>Control Arm: Standard of Care (SOC)</arm_group_label>
    <arm_group_label>Intervention Arm 1: Minimally Invasive Ablative Therapy (MIAT)</arm_group_label>
    <arm_group_label>Intervention Arm 2: Radical Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Minimally Invasive Ablative Therapy (MIAT)</intervention_name>
    <description>MIAT includes High intensity focused ultrasound (HIFU) or Cryotherapy to the prostate.&#xD;
Metastatic Directed Therapy available for use.</description>
    <arm_group_label>Intervention Arm 1: Minimally Invasive Ablative Therapy (MIAT)</arm_group_label>
    <other_name>Metastatic Directed Therapy (MDT)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Radical Therapy (Prostatectomy or Radiotherapy)</intervention_name>
    <description>Radical therapy includes: Prostatectomy (any surgical approach) or External beam radiotherapy (High dose).&#xD;
Metastatic Directed Therapy available for use.</description>
    <arm_group_label>Intervention Arm 2: Radical Therapy</arm_group_label>
    <other_name>Metastatic Directed Therapy (MDT)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosed with prostate cancer within 6 months of screening visit&#xD;
&#xD;
          2. Metastatic disease (Any T, Any N, M1+) of any grade, stage or Prostate Specific&#xD;
             Antigen (PSA) level.&#xD;
&#xD;
          3. Fit to undergo standard of care treatment for metastatic disease and both minimally&#xD;
             invasive therapy and prostate radiotherapy/prostatectomy.&#xD;
&#xD;
          4. Performance status 0-2&#xD;
&#xD;
          5. Histologically proven local tumour&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient did not undergo and/or is unable to undergo standard of care baseline imaging&#xD;
             tests for confirmation of metastatic status (CT abdomen/pelvis AND chest Xray (or CT&#xD;
             chest) AND radioisotope bone scan (or whole body imaging such as MRI or PET imaging as&#xD;
             alternative to all preceding scans mentioned here) AND prostate MRI.&#xD;
&#xD;
          2. Prior exposure to long-term androgen deprivation therapy or hormonal therapy for the&#xD;
             treatment of prostate cancer unless started within 6 months of screening visit.&#xD;
&#xD;
          3. Prior chemotherapy or local or systemic therapy for treatment of prostate cancer&#xD;
             (apart from ADT or hormonal therapy as outlined above)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hashim U Ahmed, FRCS Urol</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hashim U Ahmed, FRCS Urol</last_name>
    <phone>07517551949</phone>
    <email>atlanta@imperial.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Johanna T Sukumar, MSc</last_name>
    <phone>07517551949</phone>
    <email>atlanta@imperial.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Wirral University Teaching Hospital, Wirral University Teaching Hospital NHS Foundation Trust</name>
      <address>
        <city>Birkenhead</city>
        <zip>CH49 5PE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manal Kumar</last_name>
      <email>manalkumar@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Manal Kumar, FRCS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Glan Clwyd Hospital</name>
      <address>
        <city>Bodelwyddan</city>
        <zip>LL18 5UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jane Heron</last_name>
      <phone>01745448720</phone>
      <phone_ext>7656</phone_ext>
      <email>Jane.Heron@wales.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Nikhil Oommen, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Darent Valley Hospital</name>
      <address>
        <city>Dartford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sanjeev Madaan</last_name>
      <email>sanjeev.madaan@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Sanjeev Madaan, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Devon and Exeter NHS Trust</name>
      <address>
        <city>Exeter</city>
        <zip>EX2 5DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jane Piper</last_name>
      <email>jane.piper2@nhs.net</email>
    </contact>
    <investigator>
      <last_name>John McGrath, FRCS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Buckinghamshire Healthcare NHS Trust</name>
      <address>
        <city>High Wycombe</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anita Cserbane</last_name>
      <email>anita.cserbane@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Neil Haldar, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>West Middlesex University Hospital</name>
      <address>
        <city>Isleworth</city>
        <zip>TW7 6AF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Metod Oblak</last_name>
      <email>metod.oblak@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Mathias Winkler, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital, Kings Lynn</name>
      <address>
        <city>King's Lynn</city>
        <zip>PE30 4ET</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sophy Shedwell</last_name>
      <email>Sophy.Shedwell@qehkl.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Gail Horan, FRCR</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Chelsea and Westminster Hospital</name>
      <address>
        <city>London</city>
        <zip>SW10 9NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bijan Khoubehi</last_name>
      <email>bijan.khoubehi@chelwest.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Bijan Khoubehi, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Royal Marsden NHS Foundation Trust, Chelsea Research Centre</name>
      <address>
        <city>London</city>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vincent Khoo</last_name>
      <email>Vincent.Khoo@rmh.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Vincent Khoo, FRCR</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hashim U Ahmed, FRCS Urol</last_name>
    </contact>
    <investigator>
      <last_name>Hashim U Ahmed, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Martin J Connor, MRCS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mathias Winkler, FRCS Urol</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Taimur Shah, FRCS Urol</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>North Middlesex University Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Georgios Imseeh</last_name>
      <email>g.imseeh@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Georgios Imseeh</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Northwick Park, London North West Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Giles Hellawell, FRCS</last_name>
      <email>Giles.hellawell@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Giles Hellawell, FRCS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>St George's University Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hasan Qazi</last_name>
      <email>Hasan.Qazi2@stgeorges.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Hasan Qazi, MD FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University College London Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anita Mitra</last_name>
      <email>anita.mitra2@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Anita Mitra</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Freeman Hospital, Newcastle, Newcastle upon Tyne Hospitals NHS Foundation Trust</name>
      <address>
        <city>Newcastle</city>
        <zip>NE7 7DM</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bhavan Rai</last_name>
      <email>bhavan.rai@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Bhavan Rai, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Oxford University Hospital</name>
      <address>
        <city>Oxford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Martin Pirkl</last_name>
      <email>martin.pirkl@nds.ox.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Alastair Lamb, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Southampton General Hospital, University Hospital Southampton NHS Foundation Trust (UHS)</name>
      <address>
        <city>Southampton</city>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tim Dudderidge</last_name>
      <email>Tim.Dudderidge@uhs.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Tim Dudderidge, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sunderland Royal Hospital, City Hospitals Sunderland NHS Foundation Trust</name>
      <address>
        <city>Sunderland</city>
        <zip>SR4 7TP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sue Asterling</last_name>
      <email>sue.asterling@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Stuart McCraken, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Croydon University Hospital</name>
      <address>
        <city>Thornton Heath</city>
        <zip>CR7 7YE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ibiyemi Sadare</last_name>
      <phone>02084013000</phone>
      <phone_ext>4761</phone_ext>
      <email>ibiyemi.sadare@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Babbin John, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Southend University Hospital</name>
      <address>
        <city>Westcliff-on-Sea</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mohamed Abd-Alazeez</last_name>
      <email>mohamed.abdalazeez@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Mohamed Abd-Alazeez, FRCS Urol</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clatterbridge Cancer Centre</name>
      <address>
        <city>Wirral</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lucy Beresford</last_name>
      <email>lucy.beresford@nhs.net</email>
    </contact>
    <investigator>
      <last_name>Azman Ibrahim, FRCR</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://imperialprostate.org.uk/atlanta</url>
    <description>ATLANTA Clinical Trial Website</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>November 12, 2018</study_first_submitted>
  <study_first_submitted_qc>November 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>August 16, 2023</last_update_submitted>
  <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</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/NCT03763253
org study id: 18HH4804
nct id: NCT03763253
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Local cytoreductive treatments for men with newly diagnosed metastatic prostate cancer in
      addition to standard of care treatment
TITLE: Additional Treatments to the Local tumour for metastatic prostate cancer: Assessment
      of Novel Treatment Algorithms (ATLANTA)

      OBJECTIVES: To determine whether the addition of local treatment to the prostate (minimally
      invasive therapy or radical therapy [prostatectomy or radiotherapy]), including selective
      metastases-directed therapy, improves oncological outcomes in men receiving standard of care
      treatment for newly diagnosed metastatic prostate cancer

      PHASE: Phase II Randomised Control Trial (RCT) incorporating an internal pilot

      DESIGN: Three-arm unblinded randomised controlled trial using a positive control

      SAMPLE SIZE: 399

      POPULATION: Men who are willing to undergo local therapy to the prostate and selective
      metastases-directed therapy for metastatic prostate cancer in addition to standard care
      systemic treatment.

      STUDY HYPOTHESIS: We hypothesise that men with metastatic disease who undergo treatment of
      the local tumour in the form of either radical therapy (prostatectomy or radiotherapy) or
      minimally invasive ablative therapy (MIAT), combined with metastases directly therapy, will
      have improved survival compared to those who receive standard of treatment alone. We will be
      investigating this newly evolving treatment paradigm in a formal randomised control trial
      (RCT).

      TREATMENT/MAIN STUDY PROCEDURES: (including treatment duration and follow-up) Our pragmatic
      design ensures all eligible patients can be approached and randomised as there is no
      requirement for fitness to undergo RP. The design also incorporates the latest approach for
      standard of care as well as management of lymph nodes.

      Arm 1*: Standard of Care (SOC) treatment as determined by treating physician (positive
      control) (androgen deprivation with or without Docetaxel chemotherapy or other systemic/local
      directed standard of care treatment including but not limited to Abiraterone or
      Enzalutamide). Radiotherapy in this arm defined as palliative/cytoreductive in high volume
      metastases or to mirror STAMPEDE local radiotherapy arm in low volume metastases.

      Arm 2**: Minimally Invasive Ablative Therapy (MIAT) to local tumour / prostate in addition to
      SOC systemic treatment. Predominantly cryotherapy but based on disease characteristics, HIFU
      also. Metastases directed therapy declared prior to randomisation.

      Arm 3**: Radical therapy (Prostatectomy or External beam radiotherapy [60Gy x 20 or 74Gy + in
      32-37 weeks]) in addition to SOC systemic treatment. Modality based on physician and patient
      preference and patient co-morbidities. Metastases directed therapy declared prior to
      randomisation.

      FOLLOW-UP DURATION: Until progression or minimum 2-years or maximum 4 years whichever is
      first (or 6 months for the Pilot if the trial does not progress to Phase II).

      Prior to enrolment all patients must undergo Standard of Care (SOC) staging investigations
      for localised and metastatic disease and will need to have histologically proven local
      disease within the prostate. There will be no restriction on the type of biopsy used for
      diagnosis.

      *ADT but not chemotherapy may be initiated prior to recruitment.The decision as to which SOC
      systemic therapy regimen will be used is by the treating clinician and/or clinical team (to
      be declared upfront prior to randomisation). If radiotherapy is planned for local disease in
      some cases in the SOC arm then this will be declared upfront prior to randomisation by the
      treating physician. Similarly, if lymph node radiotherapy is to be advocated then this is to
      be declared upfront prior to randomisation by the treating physician and can be applied to
      any one of the three arms. Randomisation into a treatment arm would occur at the time of
      recruitment which would be within 3 months of starting SOC systemic therapy.

      Extra blood and urine samples will be identified using a special study number assigned to
      each patient, in such a way that the scientists analysing them will not be able to find out
      patients identity.
allocation: Randomized
intervention model: Factorial Assignment
intervention model description: Three-arm unblinded randomised controlled trial using a positive control
primary purpose: Treatment
masking: None (Open Label)
measure: Prostate cancer on post-standard of care prostate biopsy.
time frame: 6 months
description: Proportion of patients with complete pathological response, measured on post SOC (systemic therapy) prostate biopsies (Internal Pilot).
measure: Safety (Adverse Events)
time frame: 2-4 years (continuous)
description: Safety (Adverse Events), measured using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, Grade 1-5.
measure: Progression-free survival (PFS)
time frame: 2-4 years
description: Progression-free survival (PFS), measured as a composite outcome of Biochemical failure (PSA progression value) or Local progression or Lymph node progression or Bone metastases progression (new sites) or Progression or development of new distant metastases, defined as lymph nodes outside the pelvis, bone or organ involvement or Skeletal-related events confirmed as progression as in the Systemic Therapy in Advancing Or Metastatic Prostate Cancer: Evaluation Of Drug Efficacy (STAMPEDE) RCT).
measure: Urinary side effects
time frame: Baseline, week 26, 52, then at 24 months.
description: Urinary side effects, measured using the IPSS questionnaire, Score 0-35.
measure: Sexual side effects
time frame: Baseline, week 26, 52, then at 24 months.
description: Sexual side effects, measured using the IIEF15 questionnaire, Score 0-75.
measure: Rectal side effects
time frame: Baseline, week 26, 52, then at 24 months.
description: Rectal side effects, measured using the EPIC bowel and bladder questionnaire, Score 14-113.
measure: Progression (Biochemical / Radiological / Clinical)
time frame: Baseline, week 12, 26, 34, 52 then every every 24 weeks for remaining years 2 to 4 and Imaging tests at baseline and if progression is suspected by a clinician
description: Progression on PSA and imaging and impact of clinical features on progression, measured using PSA blood tests
measure: Health-related quality-of-life
time frame: Baseline, week 26, 52, then at 24 months.
description: Health-related quality-of-life, measured using EuroQol (EQ-5D-5L) questionnaire, Score 0-100.
arm group label: Control Arm: Standard of Care (SOC)
arm group type: Active Comparator
description: Standard of Care (SOC) treatment as determined by treating physician (positive control) (androgen deprivation with or without docetaxel chemotherapy or other systemic standard of care treatment including but not limited to Abiraterone or Enzalutamide).
Radiotherapy to the prostate in this arm is defined as cytoreductive (for symptom control) in high volume (>/=4) metastases or to mirror current accepted local radiotherapy dose regimens for men with low volume metastases (<4 metastases).
Metastases directed therapy will not be permitted in the control arm. Palliative radiotherapy for symptom control or for prevention of fracture will be permitted as standard clinical practice.
arm group label: Intervention Arm 1: Minimally Invasive Ablative Therapy (MIAT)
arm group type: Active Comparator
description: MIAT to prostate in form of cryotherapy or high intensity focused ultrasound (HIFU), in addition to SOC systemic treatment. No local prostate radiotherapy will be given as part of this intervention. Radiotherapy can be given subsequently for palliative reasons.
Metastatic directed therapy will be available for use in this arm (if declared at randomisation).
arm group label: Intervention Arm 2: Radical Therapy
arm group type: Active Comparator
description: Radical therapy in form of prostatectomy (any approach) or external beam radiotherapy (radical dose) in addition to SOC systemic treatment. Modality based on physician and patient preference and patient co-morbidities.
For patients undergoing radical prostatectomy no local prostate radiotherapy will be given as part of the intervention. Radiotherapy can be given subsequently for palliative reasons.
Radical radiotherapy doses in this arm will be higher than SOC.
Metastatic directed therapy will be available for use in this arm (if declared at randomisation).
intervention type: Combination Product
intervention name: Standard of Care
description: Androgen deprivation with or without docetaxel chemotherapy, Abiraterone, Enzalutamide or any other proven agent) treatment as determined by treating physician (positive control).
arm group label: Control Arm: Standard of Care (SOC)
arm group label: Intervention Arm 1: Minimally Invasive Ablative Therapy (MIAT)
arm group label: Intervention Arm 2: Radical Therapy
intervention type: Procedure
intervention name: Minimally Invasive Ablative Therapy (MIAT)
description: MIAT includes High intensity focused ultrasound (HIFU) or Cryotherapy to the prostate.
Metastatic Directed Therapy available for use.
arm group label: Intervention Arm 1: Minimally Invasive Ablative Therapy (MIAT)
other name: Metastatic Directed Therapy (MDT)
intervention type: Procedure
intervention name: Radical Therapy (Prostatectomy or Radiotherapy)
description: Radical therapy includes: Prostatectomy (any surgical approach) or External beam radiotherapy (High dose).
Metastatic Directed Therapy available for use.
arm group label: Intervention Arm 2: Radical Therapy
other name: Metastatic Directed Therapy (MDT)
criteria: 
gender: Male
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hashim U Ahmed, FRCS Urol
role: Principal Investigator
affiliation: Imperial College London
last name: Hashim U Ahmed, FRCS Urol
phone: 07517551949
email: atlanta@imperial.ac.uk
last name: Johanna T Sukumar, MSc
phone: 07517551949
email: atlanta@imperial.ac.uk
facility: 
status: Recruiting
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country: United Kingdom
url: http://imperialprostate.org.uk/atlanta
description: ATLANTA Clinical Trial Website
responsible party type: Sponsor
mesh term: Prostatic Neoplasms