ADRRAD
Research type
Research Study
Full title
Neo-adjuvant Androgen Deprivation Therapy, Pelvic Radiotherapy and RADium-223 for new presentation T1-4 N0/1 M1B adenocarcinoma of prostate (ADRRAD Trial)
IRAS ID
162270
Contact name
Joe O'Sullivan
Contact email
Sponsor organisation
Belfast Health and Social Care Trust
Eudract number
2014-000273-39
Duration of Study in the UK
2 years, 2 months, 31 days
Research summary
Research Summary
Currently, prostate cancer which has spread to bone at the time of diagnosis is managed with androgen deprivation (hormone injections) until, inevitably, these cease to be effective, at which point chemotherapy or radionuclide therapy or other novel agents may be tried. This trial seeks to test the feasibility of treating this stage of prostate cancer in a multi-modality manner from the point of diagnosis. Namely, treating with androgen deprivation (as is standard practice) plus concurrent external beam radiotherapy to prostate and pelvic lymph nodes, plus concurrent Radium223 radionuclide therapy given by intravenous injection.
Summary of Results
Short Study Title: ADRRAD Full Study Title: Neoadjuvant Androgen Deprivation Therapy, Pelvic Radiotherapy and Radium-223 for new presentation T1-4 N0/1 M1b Adenocarcinoma of Prostate.
Study Background and Treatment
Prostate cancer is a common illness and is now the most common cancer diagnosed in men. New treatments are needed to better control prostate cancer that has spread beyond the prostate gland.
At the time of the study, external beam radiation treatment to the prostate gland was not offered to men whose cancer had already spread to other areas. Research in kidney cancer showed that even when the illness had spread, treating the original site aggressively can prolong life. It was not known if this approach would work in prostate cancer.
When the effects of standard hormone treatment wear off, injectable radiation, such as Radium-223, that targets prostate cancer in bone is a treatment option.
The ADRRAD study considered two key questions:
• Is external beam radiation treatment to the prostate gland useful after the disease has already spread?
• Would injectable radiation targeting prostate cancer in bone better control disease if it is given near the start of hormone treatment?
Men already receiving standard hormone treatment would be offered two additional treatments in the ADRRAD study:
1. External Radiotherapy
External radiotherapy to the prostate gland and lymph glands in the pelvis, delivered daily, Monday – Friday, over seven and a half weeks.
2. Radium Injections
Six Radium injections, delivered at 4 weekly intervals, starting the first day of radiotherapy.
The ADRRAD study aimed to find out if this study treatment combination was feasible and safe.
ADRRAD Summary of Results version 1.0 27 July 2023
2
Study Conduct and Responsibilities
The ADRRAD study received ethical and regulatory approval and was conducted at a Cancer Centre in the UK. The recruitment target was 30 eligible participants. Participants were recruited between February 2016 and April 2019.
Key study responsibilities were:
Sponsor: Belfast Health and Social Care Trust (BHSCT)
Funder: Bayer plc, Friends of the Cancer Centre, Prostate Cancer UK Chief Investigator (CI): Professor Joe O’Sullivan, Consultant Clinical Oncologist, BHSCT / Clinical Professor, Queen’s University Belfast Study Co-ordinator: Northern Ireland Cancer Trials Network (NICTN) A Data Monitoring Committee independently reviewed detailed information about study progress and patient safety.
The Northern Ireland Cancer Research Consumer Forum (NICRCF) Prostate Cancer Research Personal and Public Involvement (PPI) Advisory Group met regularly with the CI to discuss study updates throughout the conduct of the study.
Who participated in the study?
Thirty men participated in the study. Their ages ranged from 45 to 82. All participants were receiving standard of care treatment for newly diagnosed prostate cancer that had spread to the bone. All men had prostate cancer in at least three areas of bone.
Did participants have medical problems (adverse events) taking part in the study?
Participants were assessed for adverse events when on treatment and during the first two months of follow-up. These events were most commonly gut and urinary symptoms and temporary changes in blood count. Most adverse events were mild. There were no life-threatening events or deaths.
Some participants experienced adverse events at a severe grade:
• Low white cell blood count – 3 participants (10%) • Low neutrophil (a type of white cell) blood count – 1 participant (3%) • Low platelet blood count – 1 participant (3%) • Pain or discomfort passing urine – 1 participant (3%) • Infection in the urinary track – 1 participant (3%) Adverse events (mild, moderate or severe) affecting more than a third of participants are listed below:
• Low white cell blood count (90%)
• Diarrhoea (83%)
ADRRAD Summary of Results version 1.0 27 July 2023
3
• Low neutrophil (a type of white cell) blood count (73%) • Waking at night to pass urine (60%) • Pain/discomfort passing urine (57%) • Low red cell blood count (47%) Bowel and urinary related quality of life reduced during treatment, however this was temporary, with no reduction at the end of the study.
What were the results of the study?
All thirty participants received study radiotherapy. Twenty-seven participants (90%) received six Radium injections, three (10%) received five Radium injections.
Overall, treatment was well tolerated and the impact on quality of life was acceptable. The study treatment combination was feasible and safe.
In twenty-seven participants (90%) results of a blood marker (ALP - Alkaline Phosphatase) indicated bone response during treatment.
Comparison of whole-body MRI (Magnetic Resonance Imagining) scans, before and after treatment, showed twenty-four participants (80%) had stable or reduced disease. Six months after treatment, at the end of the study, seventeen participants (57%) had stable or reduced disease.
PSA (Prostate Specific Antigen) blood tests were monitored for indication of disease progression. Participants were free of disease progression (measured from the start of standard chemotherapy or study treatment) for a period of time that ranged around 20.5 months, which was encouraging compared to results from an earlier research study involving similar patients.
How has this study helped patients and researchers?
This small study found that giving a combination of external beam radiation treatment to the prostate gland and Radium injections is feasible and safe in patients with prostate cancer that has spread to bone.
This treatment combination shows signs of anti-cancer effects and some participants benefited. A larger study is needed, such as a randomised controlled clinical trial.
Where can I learn more about this study?
Information about the ADRRAD study can be found on the internet:
Cancer Research UK website-
https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbZ0oYz60WoglvPkqIfU1HPHTUfauCq2ZPvNtWjz0kGXSOCiSOfyPyipJY7AGHLby89dR2yPuzMUTVenkV1545NCuK-2F8toiOb3oeV9OTCHgxwqsc0qxz-2BRXRhlD8O9bEA5kA6ai8oxk2G5vX0Sq6FlflmPGQ3SWQvMURrG-2FXcoF6i0FwznAhrklQG47MkD3CtTveOwWjMLOnxrpYwBBHSvj7-2BCAAK-2B9ujaEsHCberu6jEQwpa_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKDQbBEiKbnsWP5QEJl-2BTvx92VsqZ8HZ-2FialhRDH89zdQ-2BA2PJVbQ7dKV-2F8HEdZjhAzxWExj-2FpJyOKzTvyikQ1-2BGadRzPA-2BvUC1FRTK-2ByD1xIbLgZvSHj-2BeoACbaAZQ5spcew0fhSzTbVdyIhkVNqHZd30vrx-2FhBb4BpiaP6ba-2BVQ-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cab4138784b744c75bf5a08db93739cbc%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638265896982354355%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=rTfic5MmZdaA%2B%2BfBfrg9qif5qGZmgqLBYntTftlnsRE%3D&reserved=0
ADRRAD Summary of Results version 1.0 27 July 2023
4
The results are published in the Clinical Cancer Research medical journal:
https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbVSq-2F1dbX8ahKDIJ1xPLHRIgYdaC9OWJ8uDxjGLCbJIT5qNpKJI0IFjnanb656PTvdVAdcHdpV83ONs4KuE0RBn3hyElWT5-2FRa0W0SHJszmQPfz-2F2hmhHi1LLo9d69DI-2BjS3bjlyJHt8miAEdQh0Nco-3DgQRs_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKDQbBEiKbnsWP5QEJl-2BTvx2sJWxWlPs9a0igrHjLYTssf9mFSq7pACbYBYBmPPEFU-2BiCCgbmapW8lhPskiGjkoaV2l0FbCvYXU2t-2BcYxfJQH9-2FYKEyhImO40GVQJFxKvJDynYs34Aq6yrFDrqmHkk7t9PVcGbqJs7U6vdM3cXl9g-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cab4138784b744c75bf5a08db93739cbc%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638265896982354355%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=yvOzFKQn9%2FmlJN2SZcSBspKM4MVzeH1jmuYZmVii%2F9o%3D&reserved=0
For any further information please contact NICTN - Tel: 028 9615 2652 Thanks Special thanks to all the participants who took part in the study.
Thanks to the members of the NICRCF Prostate Cancer Research PPI Advisory Group.
Thanks also to the members of the ADRRAD Data Monitoring Committee, ADRRAD Trial Management Group and the NICTN and BHSCT staff involved in the study.
Has the registry been updated to include summary results?: No
If yes - please enter the URL to summary results:
If no – why not?: 04/08/2023
Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Yes
If yes, describe or provide URLs to disseminated materials: The ADRRAD study has been published in Clinical Cancer Research: American Association for Cancer Research - see link below Published paper: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbQne05VVe0UaW9iiRd6kqForFybay0szHOOGxs0eAi6cWcgibsKRBGf0fH0hXV5GJQ-3D-3DbuYk_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKDQbBEiKbnsWP5QEJl-2BTvxdBF2Tn4YLUPk35T2mP3PLYX4qR2KMrMlNIcNwio7aRpbXCSwDNbdKUzYt2u5hdMpAdqwF6-2BNj6Jq90DQga7x389u8xzW1bO3NW8vbm-2B0mbrcww15d-2F2rEZSF2-2FxRAO8m2-2BAHb57Nzewd-2Bv-2FL67WbFg-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cab4138784b744c75bf5a08db93739cbc%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638265896982354355%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=LHYOe2kIU%2FoTSya%2Bw5eTMzaL%2B%2FjqJeaLPhD36vmFCb8%3D&reserved=0The ADRRAD clinical trial was presented at the 2020 Genitourinary Cancer Symposium at ASCO
https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbd4YF9g7CD2HpXjHlYqXNYwZUs5IGfwsZJ-2F9nSIil7rZz6iPkF7ySFzL1pbey0SqF-2B9afe2cRP-2FsAOV7FIJEPIA-3Ddrri_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKDQbBEiKbnsWP5QEJl-2BTvxMvGn75dMjV9-2FsTJEOWbksxn1MlAdu70e4-2BgWFtEIZsKsRm9-2B-2BJo-2Bqo6COt9BJ-2FGiYdJa84rSDtYUgVrDwv9ozszpeaVxl-2BZR4VKJr1LcY7J3yVSzjHRw2Mt61fnPna0pt31lI2kj8iSr22t1ap1SHA-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cab4138784b744c75bf5a08db93739cbc%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638265896982354355%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=jtN%2Fq6kGzdDF9h4R73lwg8QAN6vbPU%2Bb6NKArrDSf58%3D&reserved=0
REC name
HSC REC A
REC reference
15/NI/0074
Date of REC Opinion
4 Jun 2015
REC opinion
Further Information Favourable Opinion