Additional Treatments to the Local Tumour for Metastatic Prostate Cancer: Assessment of Novel Treatment Algorithms (IP2-ATLANTA)

August 16, 2023 updated by: Imperial College London

Local Cytoreductive Treatments for Men With Newly Diagnosed Metastatic Prostate Cancer in Addition to Standard of Care Treatment

Local cytoreductive treatments for men with newly diagnosed metastatic prostate cancer in addition to standard of care treatment

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

399

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Birkenhead, United Kingdom, CH49 5PE
        • Recruiting
        • Wirral University Teaching Hospital, Wirral University Teaching Hospital NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Manal Kumar, FRCS
      • Bodelwyddan, United Kingdom, LL18 5UJ
        • Recruiting
        • Glan Clwyd Hospital
        • Contact:
        • Principal Investigator:
          • Nikhil Oommen, FRCS Urol
      • Dartford, United Kingdom
        • Recruiting
        • Darent Valley Hospital
        • Contact:
        • Principal Investigator:
          • Sanjeev Madaan, FRCS Urol
      • Exeter, United Kingdom, EX2 5DW
        • Recruiting
        • Royal Devon and Exeter NHS Trust
        • Contact:
        • Principal Investigator:
          • John McGrath, FRCS
      • High Wycombe, United Kingdom
        • Recruiting
        • Buckinghamshire Healthcare NHS Trust
        • Contact:
        • Principal Investigator:
          • Neil Haldar, FRCS Urol
      • Isleworth, United Kingdom, TW7 6AF
        • Recruiting
        • West Middlesex University Hospital
        • Contact:
        • Principal Investigator:
          • Mathias Winkler, FRCS Urol
      • King's Lynn, United Kingdom, PE30 4ET
        • Recruiting
        • Queen Elizabeth Hospital, Kings Lynn
        • Contact:
        • Principal Investigator:
          • Gail Horan, FRCR
      • London, United Kingdom, W6 8RF
        • Recruiting
        • Imperial College Healthcare NHS Trust
        • Contact:
          • Hashim U Ahmed, FRCS Urol
        • Principal Investigator:
          • Hashim U Ahmed, FRCS Urol
        • Sub-Investigator:
          • Martin J Connor, MRCS
        • Sub-Investigator:
          • Mathias Winkler, FRCS Urol
        • Sub-Investigator:
          • Taimur Shah, FRCS Urol
      • London, United Kingdom
        • Recruiting
        • University College London Hospital
        • Contact:
        • Principal Investigator:
          • Anita Mitra
      • London, United Kingdom, SW10 9NH
        • Recruiting
        • Chelsea And Westminster Hospital
        • Contact:
        • Principal Investigator:
          • Bijan Khoubehi, FRCS Urol
      • London, United Kingdom, SW3 6JJ
        • Recruiting
        • The Royal Marsden NHS Foundation Trust, Chelsea Research Centre
        • Contact:
        • Principal Investigator:
          • Vincent Khoo, FRCR
      • London, United Kingdom
        • Recruiting
        • Northwick Park, London North West Healthcare NHS Trust
        • Contact:
        • Principal Investigator:
          • Giles Hellawell, FRCS
      • London, United Kingdom
        • Recruiting
        • North Middlesex University Hospital
        • Contact:
        • Principal Investigator:
          • Georgios Imseeh
      • London, United Kingdom
        • Recruiting
        • St George'S University Hospital
        • Contact:
        • Principal Investigator:
          • Hasan Qazi, MD FRCS Urol
      • Newcastle, United Kingdom, NE7 7DM
        • Recruiting
        • Freeman Hospital, Newcastle, Newcastle upon Tyne Hospitals NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Bhavan Rai, FRCS Urol
      • Oxford, United Kingdom
        • Recruiting
        • Oxford University Hospital
        • Contact:
        • Principal Investigator:
          • Alastair Lamb, FRCS Urol
      • Southampton, United Kingdom, SO16 6YD
        • Recruiting
        • Southampton General Hospital, University Hospital Southampton NHS Foundation Trust (UHS)
        • Contact:
        • Principal Investigator:
          • Tim Dudderidge, FRCS Urol
      • Sunderland, United Kingdom, SR4 7TP
        • Recruiting
        • Sunderland Royal Hospital, City Hospitals Sunderland NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Stuart McCraken, FRCS Urol
      • Thornton Heath, United Kingdom, CR7 7YE
        • Recruiting
        • Croydon University Hospital
        • Contact:
        • Principal Investigator:
          • Babbin John, FRCS Urol
      • Westcliff-on-Sea, United Kingdom
        • Recruiting
        • Southend University Hospital
        • Contact:
        • Principal Investigator:
          • Mohamed Abd-Alazeez, FRCS Urol
      • Wirral, United Kingdom
        • Recruiting
        • Clatterbridge Cancer Centre
        • Contact:
        • Principal Investigator:
          • Azman Ibrahim, FRCR

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Diagnosed with prostate cancer within 6 months of screening visit
  2. Metastatic disease (Any T, Any N, M1+) of any grade, stage or Prostate Specific Antigen (PSA) level.
  3. Fit to undergo standard of care treatment for metastatic disease and both minimally invasive therapy and prostate radiotherapy/prostatectomy.
  4. Performance status 0-2
  5. Histologically proven local tumour

Exclusion Criteria:

  1. Patient did not undergo and/or is unable to undergo standard of care baseline imaging tests for confirmation of metastatic status (CT abdomen/pelvis AND chest Xray (or CT chest) AND radioisotope bone scan (or whole body imaging such as MRI or PET imaging as alternative to all preceding scans mentioned here) AND prostate MRI.
  2. Prior exposure to long-term androgen deprivation therapy or hormonal therapy for the treatment of prostate cancer unless started within 6 months of screening visit.
  3. Prior chemotherapy or local or systemic therapy for treatment of prostate cancer (apart from ADT or hormonal therapy as outlined above)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control Arm: Standard of Care (SOC)

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.
Combination product: Standard of Care
Androgen deprivation with or without docetaxel chemotherapy, Abiraterone, Enzalutamide or any other proven agent) treatment as determined by treating physician (positive control).
Active Comparator: Intervention Arm 1: Minimally Invasive Ablative Therapy (MIAT)

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).
Combination product: Standard of Care
Androgen deprivation with or without docetaxel chemotherapy, Abiraterone, Enzalutamide or any other proven agent) treatment as determined by treating physician (positive control).
Procedure: Minimally Invasive Ablative Therapy (MIAT)

MIAT includes High intensity focused ultrasound (HIFU) or Cryotherapy to the prostate.

Metastatic Directed Therapy available for use.

Other Names:
  • Metastatic Directed Therapy (MDT)
Active Comparator: Intervention Arm 2: Radical Therapy

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).
Combination product: Standard of Care
Androgen deprivation with or without docetaxel chemotherapy, Abiraterone, Enzalutamide or any other proven agent) treatment as determined by treating physician (positive control).
Procedure: Radical Therapy (Prostatectomy or Radiotherapy)

Radical therapy includes: Prostatectomy (any surgical approach) or External beam radiotherapy (High dose).

Metastatic Directed Therapy available for use.

Other Names:
  • Metastatic Directed Therapy (MDT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prostate cancer on post-standard of care prostate biopsy.
Time Frame: 6 months
Proportion of patients with complete pathological response, measured on post SOC (systemic therapy) prostate biopsies (Internal Pilot).
6 months
Safety (Adverse Events)
Time Frame: 2-4 years (continuous)
Safety (Adverse Events), measured using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, Grade 1-5.
2-4 years (continuous)
Progression-free survival (PFS)
Time Frame: 2-4 years
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).
2-4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urinary side effects
Time Frame: Baseline, week 26, 52, then at 24 months.
Urinary side effects, measured using the IPSS questionnaire, Score 0-35.
Baseline, week 26, 52, then at 24 months.
Sexual side effects
Time Frame: Baseline, week 26, 52, then at 24 months.
Sexual side effects, measured using the IIEF15 questionnaire, Score 0-75.
Baseline, week 26, 52, then at 24 months.
Rectal side effects
Time Frame: Baseline, week 26, 52, then at 24 months.
Rectal side effects, measured using the EPIC bowel and bladder questionnaire, Score 14-113.
Baseline, week 26, 52, then at 24 months.
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
Progression on PSA and imaging and impact of clinical features on progression, measured using PSA blood tests
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
Health-related quality-of-life
Time Frame: Baseline, week 26, 52, then at 24 months.
Health-related quality-of-life, measured using EuroQol (EQ-5D-5L) questionnaire, Score 0-100.
Baseline, week 26, 52, then at 24 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Collaborators

Wellcome Trust

Investigators

  • Principal Investigator: Hashim U Ahmed, FRCS Urol, Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 10, 2019

Primary Completion (Estimated)

August 31, 2026

Study Completion (Estimated)

January 31, 2027

Study Registration Dates

First Submitted

November 12, 2018

First Submitted That Met QC Criteria

November 30, 2018

First Posted (Actual)

December 4, 2018

Study Record Updates

Last Update Posted (Actual)

August 21, 2023

Last Update Submitted That Met QC Criteria

August 16, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18HH4804

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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