Local cytoreductive treatments for men with newly diagnosed metastatic prostate cancer in addition to standard of care treatment
| ISRCTN | ISRCTN58401737 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN58401737 |
| ClinicalTrials.gov (NCT) | NCT03763253 |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | 18HH4804 |
| Sponsor | Imperial College London |
| Funder | Wellcome Trust |
- Submission date
- 09/11/2018
- Registration date
- 21/11/2018
- Last edited
- 24/09/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Contact information
Scientific
Imperial College London
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
 ORCID ID |
0000-0003-1674-6723 |
|---|---|
| Phone | +44 (0)2033115473 |
| atlanta@imperial.ac.uk |
Scientific
Imperial College London
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
Scientific
Imperial College London
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
Public
Imperial College London
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Three-arm unblinded randomized controlled trial using a positive control |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Additional Treatments to the Local tumour for metastatic prostate cancer: Assessment of Novel Treatment Algorithms |
| Study acronym | IP2 - ATLANTA |
| Study objectives | The trialists 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. They will be investigating this newly evolving treatment paradigm in a formal randomised control trial (RCT). |
| Ethics approval(s) | Approved 22/01/2019, Wales Research Ethics Committee 5 Bangor (Health and Care Research Wales Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB; +44(0)2920 785736; WalesREC5@wales.nhs.uk), ref: 19/WA/0005 |
| Health condition(s) or problem(s) studied | Prostate cancer; metastatic disease (Any T, Any N, M1+) of any grade, stage or Prostate Specific Antigen (PSA) level |
| Intervention | Current interventions as of 23/08/2023: Stratified randomisation via the electronic platform REDCap database. Intervention Arm 1: Minimally Invasive Ablative Therapy (MIAT) to prostate in addition to SOC systemic treatment. The exact treatment protocol and modality used (cryotherapy or high intensity focused ultrasound, HIFU) will be set within the MIAT SOP. For those patients who are undergoing MIAT no local prostate radiotherapy will be given as part of the intervention. Radiotherapy can be given subsequently for palliative reasons. MIAT can be provided by a site other than the recruiting site with follow-up visits at recruiting site. Intervention Arm 2: Radical therapy (prostatectomy or external beam radiotherapy [Prostate radiotherapy using a dose of external beam radiotherapy of 60Gy/20Fr over 27 days OR 74-78Gy in 2Gy per fraction with or without simultaneous nodal radiotherapy, as defined in Local Radiotherapy SOP]) in addition to SOC systemic treatment. Modality based on physician and patient preference and patient co-morbidities. Radiotherapy or surgery can be provided by a site other than the recruiting site with follow-up visits at the recruiting site. The surgical technique is at the discretion and expertise of the surgical team but will be laid down in the Prostatectomy SOP. For those patients who are undergoing radical prostatectomy no local prostate radiotherapy will be given as part of the intervention. Radiotherapy can be given subsequently for palliative reasons. The radiotherapy doses and protocol in this arm will be higher defined in the Radiotherapy Intervention Arm 2 SOP. Metastases Directed Therapy (Intervention Arm 1 and 2): In both intervention arms 1 and 2, metastases directed therapy (MDT) may be used but intent to use MDT to be declared prior to randomisation. In the case of a metastatic recurrence after MDT, a re-treatment with MDT would be allowed if there were new metastatic areas/locations. The imaging reporting of metastases as well as doses and protocol for MDT as defined in and determined by an Imaging Reporting SOP and a Metastases-Directed Therapy SOP. Treatment duration of trial therapies: Prostatectomy 1 day; Radiotherapy 4 to 7.5 weeks; Minimally invasive therapy (MIAT) 1 day [68Ga]PSMA-11 PET-CT Sub study--Now completed: The trialists will also ask men in the pilot part of ATLANTA if they are willing to undergo a PSMA PET scan. They want to see if this scan might be as accurate in detecting residual disease as prostate biopsies and standard body scans, like MRI, CT or bone scans. This however is optional and participants will be told that they do not have to agree to take part in this optional research, but can still take part in the ATLANTA study. The tests required for this exploratory research will be explained to patients prior to consent in the Patient Information Sheet and verbally by clinician. The target recruitment for this study is 25 patients. Previous interventions from 08/07/2021 to 23/08/2023: Stratified randomisation via the electronic platform known as the InForm database. Intervention Arm 1: Minimally Invasive Ablative Therapy (MIAT) to prostate in addition to standard of care systemic treatment. The exact treatment protocol and modality used (cryotherapy or high intensity focused ultrasound, HIFU) will be set within the MIAT SOP. For those patients who are undergoing MIAT no local prostate radiotherapy will be given as part of the intervention. Radiotherapy can be given subsequently for palliative reasons. Intervention Arm 2: Radical therapy with either prostatectomy or external beam radiotherapy (high radical dose set out in Radiotherapy Intervention Arm 2 SOP) in addition to standard of care systemic treatment. Modality based on physician and patient preference and patient co-morbidities. The surgical technique is at the discretion and expertise of the surgical team but will be laid down in the Prostatectomy SOP. For those patients who are undergoing radical prostatectomy no local prostate radiotherapy will be given as part of the intervention. Radiotherapy can be given subsequently for palliative reasons. Metastases Directed Therapy (Intervention Arm 1 and 2): In both intervention arms 1 and 2, metastases directed therapy (MDT) may be used but intent to use MDT to be declared prior to randomisation. In the case of a metastatic recurrence after MDT, a re-treatment with MDT would be allowed if there were new metastatic areas/locations. The imaging reporting of metastases as well as doses and protocol for MDT will be defined and determined by an Imaging Reporting SOP and a Metastases-Directed Therapy SOP. In total, 80 men will be approached in 10 UK centre to estimate recruitment rate, acceptability of the trial randomisation, reported toxicities and adherence to trial interventions in a pilot phase- this phase has now been successfully completed. They will also be included into the main phase where 918 will be recruited over 30 UK centres- current phase. Participants will remain in the study for a maximum of 4 years. The aims are to see whether men will participate in this trial (pilot) before a larger trial (main) is run, and the impact of these treatments on quality of life. [68Ga]PSMA-11 PET-CT substudy: The trialists will also ask men in the pilot part of ATLANTA if they are willing to undergo a PSMA PET scan. They want to see if this scan might be as accurate in detecting residual disease as prostate biopsies and standard body scans, like MRI, CT or bone-scans. This however is optional and participants will be told that they do not have to agree to take part in this optional research, but can still take part in the ATLANTA study. The tests required for this exploratory research will be explained to patients prior to consent in the Patient Information Sheet and verbally by clinician. Target recruitment for this study is 25 patients. This substudy has now successfully been completed and we are not recruiting into this as we are now in the main phase of the trial. Previous interventions: Stratified randomisation via the electronic platform known as the InForm database. Intervention Arm 1: Minimally Invasive Ablative Therapy (MIAT) to prostate in addition to standard of care systemic treatment. The exact treatment protocol and modality used (cryotherapy or high intensity focused ultrasound, HIFU) will be set within the MIAT SOP. For those patients who are undergoing MIAT no local prostate radiotherapy will be given as part of the intervention. Radiotherapy can be given subsequently for palliative reasons. Intervention Arm 2: Radical therapy with either prostatectomy or external beam radiotherapy (high radical dose set out in Radiotherapy Intervention Arm 2 SOP) in addition to standard of care systemic treatment. Modality based on physician and patient preference and patient co-morbidities. The surgical technique is at the discretion and expertise of the surgical team but will be laid down in the Prostatectomy SOP. For those patients who are undergoing radical prostatectomy no local prostate radiotherapy will be given as part of the intervention. Radiotherapy can be given subsequently for palliative reasons. Metastases Directed Therapy (Intervention Arm 1 and 2): In both intervention arms 1 and 2, metastases directed therapy (MDT) may be used but intent to use MDT to be declared prior to randomisation. In the case of a metastatic recurrence after MDT, a re-treatment with MDT would be allowed if there were new metastatic areas/locations. The imaging reporting of metastases as well as doses and protocol for MDT will be defined and determined by an Imaging Reporting SOP and a Metastases-Directed Therapy SOP. In total, 80 men will be approached in 10 UK centre to estimate recruitment rate, acceptability of the trial randomisation, reported toxicities and adherence to trial interventions in a pilot phase. They will also be included into the main phase where 918 will be recruited over 30 UK centres. Participants will remain in the study for a maximum of 4 years. The aims are to see whether men will participate in this trial (pilot) before a larger trial (main) is run, and the impact of these treatments on quality of life. [68Ga]PSMA-11 PET-CT substudy: The trialists will also ask men in the pilot part of ATLANTA if they are willing to undergo a PSMA PET scan. They want to see if this scan might be as accurate in detecting residual disease as prostate biopsies and standard body scans, like MRI, CT or bone-scans. This however is optional and participants will be told that they do not have to agree to take part in this optional research, but can still take part in the ATLANTA study. The tests required for this exploratory research will be explained to patients prior to consent in the Patient Information Sheet and verbally by clinician. Target recruitment for this study is 25 patients. |
| Intervention type | Mixed |
| Primary outcome measure(s) |
Internal Pilot: |
| Key secondary outcome measure(s) |
1. Urinary, sexual and rectal side effects, measured using the IPSS, IIEF15 and EPIC questionnaires at baseline, week 26, week 28, week 34, then every 12 weeks for first year and every 24 weeks for remaining years 2 to 4 |
| Completion date | 31/08/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Male |
| Target sample size at registration | 399 |
| Total final enrolment | 433 |
| Key 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 |
| Key exclusion criteria | Added 23/08/2023: Current exclusion criteria as of 06/10/2021: 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 X-ray (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) Previous exclusion criteria from 08/02/2021 to 06/10/2021: 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 X-Ray (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 4 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 in Exclusion Criteria 2) Previous 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 X-Ray (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 3 months of randomisation 3. Prior chemotherapy or local or systemic therapy for treatment of prostate cancer (apart from ADT or hormonal therapy as outlined above in Exclusion Criteria 2) |
| Date of first enrolment | 10/04/2019 |
| Date of final enrolment | 31/08/2024 |
Locations
Countries of recruitment
- United Kingdom
- England
- Wales
Study participating centres
London
W6 8RF
United Kingdom
Southampton
SO16 6YD
United Kingdom
Sunderland
SR4 7TP
United Kingdom
King's Lynn
PE30 4ET
United Kingdom
Harrow
HA1 3UJ
United Kingdom
Freeman Rd
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Arrowe Park Rd
Birkenhead
CH49 5PE
United Kingdom
Exeter
EX2 5DW
United Kingdom
Thornton Heath
London
CR7 7YE
United Kingdom
Chelsea
London
SW3 6JJ
United Kingdom
Unit 5 Gwenfro
Wrexham
LL13 7YP
United Kingdom
London
SW10 9NH
United Kingdom
Isleworth
TW7 6A
United Kingdom
London
SE5 9RS
United Kingdom
Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom
Dartford
DA2 8DA
United Kingdom
High Wycombe
HP11 2TT
United Kingdom
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
London
NW1 2PG
United Kingdom
Sterling Way
London
N18 1QX
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Hashim U Ahmed (hashim.ahmed@imperial.ac.uk). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 26/07/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
24/09/2025: Total final enrolment added.
10/09/2025: Contact details updated. The sponsor was changed from Imperial College London and Imperial College Healthcare NHS Trust to Imperial College London.
23/08/2023: The following changes have been made:
1. The interventions and exclusion criteria were updated.
2. The target number of participants was changed from 918 to 399.
3. The Clatterbridge Cancer Centre NHS Foundation Trust, Darent Valley Hospital, Wycombe Hospital, Oxford University Hospitals NHS Foundation Trust, University College London Hospitals NHS Foundation Trust, and North Middlesex University Hospital Trust were added to the study participating centres.
05/04/2022: The following changes have been made:
1. The recruitment end date has been changed from 30/04/2022 to 31/08/2024.
2. The overall trial end date has been changed from 01/03/2024 to 31/08/2026.
3. The intention to publish date has been changed from 01/03/2025 to 31/01/2027.
08/07/2021: The following changes have been made:
1. The scientific title has been changed from "Adjuvant Treatments to the Local tumour for metastatic prostate cancer: Assessment of Novel
Treatment Algorithms" to "Additional Treatments to the Local tumour for metastatic prostate cancer: Assessment of Novel Treatment Algorithms".
2. The trial participating centre "Kings College Hospital" has been added.
3. The interventions have been updated.
4. The EudraCT number has been added.
08/02/2021: The following changes were made to the trial record:
1. The scientific title was changed from "Adjuvant Treatments to the Local tumour for metastatic prostate cancer: Assessment of Novel Treatment Algorithms" to "Adjuvant Treatments to the Local tumour for metastatic prostate cancer: Assessment of Novel Treatment Algorithms".
2. The recruitment end date was changed from 01/01/2021 to 30/04/2022.
3. The exclusion criteria were changed.
4. The following trial participating centres were removed: Guys and St Thomas Hospital, The Royal United Hospital, Worcestershire Acute Hospitals NHS Trust, University Hospital Coventry, Wexham Park Hospital, Norfolk and Norwich University Hospital, The Royal Marsden NHS Foundation Trust/
5. The following trial participating centres were added: West Middlesex University Hospital, Chelsea and Westminister, Glan Clwyd Hospital, Royal Marsden Hospital, Croydon University Hospital.
15/04/2020: The public contact has been updated.
06/08/2019: Cancer Research UK lay summary link added to plain English summary field.
05/08/2019: Internal review.
22/07/2019: The trial participating centre was added: The Royal Marsden NHS Foundation Trust.
19/07/2019: The following changes were made to the trial record:
1. The following trial participating centres were removed: St George's Hospital, St George's Healthcare NHS Trust, Ashford and St Peters, Broomfield Hospital, Princess Alexandra Hospital, Lister Hospital, Glan Clwyd Hospital (Betsi Cadwaladr University Health Board), Wrexham Maelor Hospital (Betsi Cadwaladr University Health Board).
2. The following trial participating centres were added: Northwick Park, London North West Healthcare NHS Trust, The Royal United Hospital, Royal United Hospitals Bath NHS Foundation Trust, Freeman Hospital, Newcastle, Newcastle upon Tyne Hospitals NHS Foundation Trust, Wirral University Teaching Hospital, Wirral University Teaching Hospital NHS Foundation Trust, Worcestershire Acute Hospitals NHS Trust, University Hospital Coventry, University Hospitals Coventry & Warwickshire NHS Trust (UHCW), Royal Devon and Exeter NHS Trust, Wexham Park Hospital, Frimley Health NHS Foundation Trust, Norfolk and Norwich University Hospital, Norfolk & Norwich University Hospital NHS Foundation Trust.
17/07/2019: The following changes were made to the trial record:
1. The ethics approval was added.
2. The recruitment start date was changed from 01/01/2019 to 10/04/2019.
21/06/2019: Internal review.
23/05/2019: ClinicalTrials.gov number added.
05/04/2019: Internal review.
05/03/2019: Internal review.
