Condition category
Cancer
Date applied
09/11/2018
Date assigned
21/11/2018
Last edited
22/11/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

http://imperialprostate.org.uk/atlanta

Contact information

Type

Scientific

Primary contact

Prof Hashim U. Ahmed

ORCID ID

http://orcid.org/0000-0003-1674-6723

Contact details

Imperial College London
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom
+44 (0)2033115473
atlanta@imperial.ac.uk

Type

Scientific

Additional contact

Mr Taimur Shah

ORCID ID

Contact details

Imperial College London
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom

Type

Scientific

Additional contact

Mr Martin J. Connor

ORCID ID

Contact details

Imperial College London
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom

Type

Public

Additional contact

Ms Johanna Sukumar

ORCID ID

Contact details

Imperial College London
Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

18HH4804

Study information

Scientific title

Adjuvant Treatments to the Local tumour for metastatic prostate cancer: Assessment of Novel Treatment Algorithms

Acronym

IP2 - ATLANTA

Study hypothesis

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

Planned submission to a London Ethics (appointment currently pending) in November 2018

Study design

Three-arm unblinded randomised controlled trial using a positive control

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a Participant Information Sheet

Condition

Prostate cancer; metastatic disease (Any T, Any N, M1+) of any grade, stage or Prostate Specific Antigen (PSA) level

Intervention

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

Phase

Drug names

Primary outcome measure

Internal Pilot:
1. Compliance to randomised arm, measured using the electronic Case Report Form on a monthly basis.
2. Recruitment and randomisation rate, measured using the electronic Case Report Form on a monthly basis.
3. Safety (adverse events), measured using the electronic Case Report Form at baseline, week 12, week 26, week 28, week 32, week 34 then every 12 weeks for first year and every 24 weeks for remaining years 2 to 4 for all patients.
4. Proportion of patients with complete pathological response, measured on post SOC systemic therapy prostate biopsies at 6-9 months.

Phase II:
1. Progression-free survival (PFS), with progression defined 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. PFS will be assessed from the time of enrollment to the end of the study. Depending on when the patient is recruited, the follow-up duration will be 2-4 years.

Secondary outcome measures

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
2. Patient-reported outcomes, measured using the IPSS, IIEF15, EPIC Bowel and Bladder, EQ-5D-5L, EORTC QLQ-FA12 (Fatigue), EORTC QLQ-ELD14 (Elderly), EORTC QLQ-C30 (General), EORTC QLQ PR25 (Prostate), EORTC QLQ-BM22 (Bone Metastases) 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
3. Progression on PSA and imaging and impact of clinical features on progression, measured using PSA blood tests at baseline, week 12, 26, 34 then every 12 weeks for first year and every 24 weeks for remaining years 2 to 4 and Imaging tests at baseline and if progression is suspected by a clinician
4. Health-related quality-of-life, measured using the IPSS, IIEF15, EPIC Bowel and Bladder, EQ-5D-5L, EORTC QLQ-FA12 (Fatigue), EORTC QLQ-ELD14 (Elderly), EORTC QLQ-C30 (General), EORTC QLQ PR25 (Prostate), EORTC QLQ-BM22 (Bone Metastases) 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
5. Data on costs and resource utilisation for future cost-effectiveness analysis, measured as defined in the statistical analysis plan at trial completion

Overall trial start date

23/02/2017

Overall trial end date

01/03/2024

Reason abandoned (if study stopped)

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

918

Participant 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)

Recruitment start date

01/01/2019

Recruitment end date

01/01/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Charing Cross Hospital, Imperial College Healthcare NHS Trust
Fulham Palace Road, Hammersmith
London
W6 8RF
United Kingdom

Trial participating centre

St George's Hospital, St George's Healthcare NHS Trust
Blackshaw Road
London
SW17 0QT
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Ashford and St Peters
Guildford Road, Lyne
Chertsey
KT16 0PZ
United Kingdom

Trial participating centre

Broomfield Hospital
Court Road, Broomfield
Chelmsford
CM1 7ET
United Kingdom

Trial participating centre

Sunderland Royal Hospital 
Kayll Road
Sunderland
SR4 7TP
United Kingdom

Trial participating centre

Cambridge Queen Elizabeth Hospital, Kings Lynn
Gayton Road, King's Lynn
King's Lynn
PE30 4ET
United Kingdom

Trial participating centre

Guys and St Thomas Hospital
Westminster Bridge Road, Lambeth
London
SE1 7EH
United Kingdom

Trial participating centre

Princess Alexandra Hospital
Hamstel Road
Harlow
CM20 1QX
United Kingdom

Trial participating centre

Lister Hospital
Coreys Mill Lane
Stevenage
SG1 4AB
United Kingdom

Trial participating centre

Glan Clwyd Hospital (Betsi Cadwaladr University Health Board)
Rhuddlan Road
Rhyl
LL18 5UJ
United Kingdom

Trial participating centre

Wrexham Maelor Hospital (Betsi Cadwaladr University Health Board)
Croesnewydd Road
Wrexham
LL13 7TD
United Kingdom

Sponsor information

Organisation

Imperial College London and Imperial College Healthcare NHS Trust

Sponsor details

Joint Research Compliance Office
Room 215
Level 2
Medical School Building
Norfolk Place
London
W2 1PG
United Kingdom
+44 (0)2075949459
becky.ward@imperial.ac.uk

Sponsor type

University/education

Website

https://www.imperial.ac.uk/joint-research-compliance-office/

Funders

Funder type

Research organisation

Funder name

Wellcome Trust

Alternative name(s)

Wellcome

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Main study:
When the study is completed the results will be analysed and presented at international meetings before being published in a medical journal. Large studies such as this take many years to complete and for the final results to appear. When the study results are concluded, they will be presented by clinicians and patient groups, and posted on our website for patients to access. The trial website is available via a link on this page. A newsletter presenting the salient findings in an easy-to-read style will be written in conjunction with the patient representative at study end. This will be circulated to all consenting participants by email or letter depending on their preferences. Findings will be presented through the websites and newsletter of a number of supporting organisations of which our team members have links including Prostate Cancer UK, Maggie’s support group, Pelican Cancer Foundation and CRUK. The social media presence of organisations involved will be used to highlight news about the trial.

Sub-study results:
After completion of the study the results may be presented at national/international scientific meetings or published in a leading medical journal. The patient will not be identified in any report/publication, and the patient is made aware that the results of some of the tests done as a part of this research may not be available to them individually. Data and images obtained from the scans may be used in an anonymous form for future research, including that carried out by commercial healthcare companies. The participants will not be contacted by any companies carrying out such research and they will not be given access to the participants medical records. It is also made clear in the sub-study PIS that if any inventions resulting in commercial gain emerge from any of this research the participant will not be eligible to benefit financially from these discoveries.

IPD sharing statement
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).

Intention to publish date

01/03/2025

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes