A phase III randomised controlled trial of prostate and pelvis versus prostate alone radiotherapy with or without prostate boost
| ISRCTN | ISRCTN80146950 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN80146950 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 219463 |
| Central Portfolio Management System (CPMS) | CPMS 34511 |
| Sponsor | Institute Of Cancer Research |
| Funder | Cancer Research UK |
- Submission date
- 08/01/2018
- Registration date
- 18/01/2018
- Last edited
- 27/11/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Contact information
Public
The Institute of Cancer Research: Royal Cancer Hospital
123 Old Brompton Road
London
SW7 3RP
United Kingdom
| Phone | +44 20 7352 8133 |
|---|---|
| PIVOTALboost-icrctsu@icr.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomized; Interventional; Design type: Treatment, Radiotherapy |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | A phase III randomised controlled trial of prostate and pelvis versus prostate alone radiotherapy with or without prostate boost |
| Study acronym | PIVOTALBoost |
| Study objectives | The primary objective of PIVOTALboost is to assess whether pelvic lymph node radiotherapy with or without dose escalation to the prostate with HDR, HDR incorporating a focal boost or focal boost IMRT when delivered at multiple centres can lead to improved failure free survival with similar levels of bladder (genitourinary) and bowel (gastrointestinal) side effects experienced by patients. |
| Ethics approval(s) |
Approved 19/05/2017, London-Chelsea Research Ethics Committee (Bristol Centre, Level 3, Block B, Whitefriars, Lewins Mead, Bristol, BS1 2NT, United Kingdom; +44 (0)207 1048055; chelsea.rec@hra.nhs.uk), ref: 17/LO/0731 |
| Health condition(s) or problem(s) studied | Prostate cancer |
| Intervention | Participants are allocated to one of the following treatment arms: A: Prostate alone Intensity-modulated radiation therapy (IMRT) B: Prostate and pelvic IMRT C: Prostate IMRT and prostate boost D: Prostate and pelvic IMRT and prostate boost. Randomisation into arms C and D depend on the boost volume identified by MRI (suitable for focal boost or not), availability of focal HDR or IMRT and patient suitability in case of HDR Participants are eligible for entry into one of the following randomisation options according to: 1. Boost volume (whether the tumour volume identified on the staging MRI is suitable for focal boost or not), 2. Suitability and availability of HDR (e.g. patient not suitable for HDR brachytherapy or any other clinical reason) and, 3. Type of focal boost (IMRT or HDR brachytherapy). In centres with no access to HDR or focal IMRT boost, all patients will enter randomisation option 1 (irrespective of having a suitable boost or not). Randomisation Option 1 (Pelvic node randomisation): No suitable focal boost volume on the staging MRI* and not suitable for HDR brachytherapy. Randomisation Option 2a (Pelvic node and whole gland boost): No suitable focal boost volume on the staging MRI* and suitable for HDR. Randomisation Option 2b (Pelvic node and focal boost randomisation): Suitable focal boost volume. The study doctor explains whether the patient is suitable for brachytherapy to the whole prostate and /or focal boost treatment. It depends on many factors: the patient’s fitness, the position of the prostate in the pelvis, previous prostate surgery, the appearance of the cancer and the availability of the treatment techniques at the local cancer centre. For patients without cancer nodules suitable for focal boost treatment: Patients without a prostate nodule on the MRI scan can be offered brachytherapy (short term internal radiation) to the whole prostate. This procedure is also called high dose rate (HDR) brachytherapy. This treatment delivers a high radiation dose to the prostate. It is combined with external beam radiotherapy to the prostate (15 fractions) or to the prostate and pelvic lymph nodes (20 fractions). For patients with cancer nodules suitable for focal boost treatment: The radiotherapy dose can be increased to the area in the prostate containing the cancer; the rest of the prostate receives the standard dose. The focal boost treatment can be given either with HDR brachytherapy or external beam radiotherapy. The post treatment follow up period is 10 years. Added 27/11/2025: Additional Data Linkage Information: Participants from this trial will also be included in the INTERACT project which will link to their data held by NHS England. For more information, please see the INTERACT website: https://www.icr.ac.uk/interact. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure(s) |
Failure-free survival is measured by the time to first biochemical failure, recommencement of androgen deprivation therapy, local recurrence, lymph node/pelvic recurrence, distant metastases or death due to prostate cancer for up to 10 years. |
| Key secondary outcome measure(s) |
1. Time to loco-regional recurrence; time to biochemical failure or prostate recurrence; metastatic relapse free survival; overall and prostate cancer specific survival; time to recommencement of androgen deprivation therapy is measured using clinical assessment of disease status up to 10 years |
| Completion date | 31/12/2029 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | Male |
| Target sample size at registration | 2229 |
| Total final enrolment | 2232 |
| Key inclusion criteria | 1. Histologically confirmed, previously untreated, non-metastatic adenocarcinoma of the prostate using the Gleason scoring or grade group system (histological confirmation can be based on tissue taken at any time, but a re-biopsy should be considered if the biopsy is more than 12 months old). 2. PSA <50 ng/ml prior to starting ADT. 3. NCCN localised high risk or locally advanced disease: T3a, T3b or T4 N0M0 (clinical and/or MRI) and/or Dominant Gleason 4 or 5 (grade group 3, 4, or 5) and/or PSA >20; or 3.1. NCCN intermediate risk disease: T2b-c N0M0, and/or Gleason 3+4 (grade group 2) and /or PSA 10-20 ng/ml and Adverse feature, for example: Maximum tumour length (MTL) >6 mm and/or 50% biopsy cores positive and / or PI-RADS score 3, 4 or 5, DIL lesion >10mm axial dimension on staging MRI. 4. Age ≥18 years 5. Signed, written informed consent 6. WHO performance status 0-2 (Appendix 1) |
| Key exclusion criteria | 1. Prior radiotherapy to the prostate or pelvis 2. Prior radical prostatectomy 3. Prior ADT for > 6 months at consent (as patients will need to commence radiotherapy at months 3-5 (maximum 7) following start of ADT) 4. Adjuvant docetaxel chemotherapy 5. Radiologically suspicious or pathologically confirmed lymph node involvement 6. Evidence of metastatic disease 7. Life expectancy < 5 years 8. Bilateral hip prostheses or any other implants/hardware that would introduce substantial CT artifacts and would make pelvic node planning more difficult 9. For patients having fiducials inserted: Anticoagulation with warfarin/ bleeding tendency making fiducial placement or surgery unsafe in the opinion of the clinician. 10. For patients being considered for randomisation options C2 and D2 only and are undergoing a planning MRI scan: Contraindication to undergo a MRI scan. 11. For undergoing HDR brachytherapy: long-term anticoagulation therapy which cannot be temporarily stopped, prostate surgery (TURP) with a significant tissue cavity, a history of recent deep vein thrombosis or pulmonary embolus, significant cardiovascular comorbidity, unfit for prolonged general anaesthetic. 12. Medical conditions likely to make radiotherapy inadvisable e.g. inflammatory bowel disease, significant urinary symptoms 13. Previous malignancy within the last 2 years (except basal cell carcinoma or squamous cell carcinoma of the skin), or if previous malignancy is expected to significantly compromise 5 year survival 14. Any other contraindication to external beam radiotherapy to the pelvis |
| Date of first enrolment | 02/01/2018 |
| Date of final enrolment | 30/08/2024 |
Locations
Countries of recruitment
- United Kingdom
- England
- Scotland
- Wales
Study participating centres
Clatterbridge Road
Bebington
Wirral
CH63 4JY
England
Beckett Street
Leeds
LS9 7TF
England
Fulham Road
London
SW3 6JJ
England
Cardiff
CF14 2TL
Wales
Greetwell Road
Lincoln
LN2 4AX
England
Hengrave House
Newton Road
Torquay
TQ2 7AA
England
Edgbaston
Birmingham
B15 2TH
England
Taunton
TA1 5DA
England
Colney Lane
Colney
Norwich
NR4 7UY
England
Tremona Road
Southampton
SO16 6YD
England
Freeman Road
High Heaton
Newcastle
NE7 7DN
England
Cambridge
CB2 0QQ
England
Pond Street
London
NW3 2QG
England
Eastern Road
Brighton
BN2 5BE
England
Maidstone
ME16 9QQ
England
Egerton Road
Surrey
Guildford
GU2 7XX
England
Ipswich
IP4 5PD
England
250 Euston Road
London
NW1 2PG
England
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
England
Mansfield Road
Sutton-in-ashfield
NG17 4JL
England
Herries Road
Sheffield
S5 7AU
England
Inverness
IV2 3BW
Scotland
The Royal London Hospital
Whitechapel
London
E1 1BB
England
Holdforth Road
Hartlepool
TS24 9AH
England
Marton Road
Middlesbrough
TS4 3BW
England
Turner Road
Colchester
CO4 5JL
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | 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
27/11/2025: The interventions were updated.
12/09/2024: The following changes have been made:
1. IRAS number added.
2. Study website added.
3. The target number of participants was changed from "Planned Sample Size: 1952; UK Sample Size: 1952".
4. The total final enrolment was added.
5. The recruitment end date has been changed from 31/12/2024 to 30/08/2024.
6. The following study participating centres were added: University Hospitals Birmingham Nhs Foundation Trust, Sherwood Forest Hospitals NHS Foundation Trust, Sheffield Teaching Hospitals NHS Foundation Trust, Highland Health Board, NIHR CLAHRC North Thames, North Tees and Hartlepool NHS Foundation Trust, South Tees Hospitals NHS Foundation Trust and Cuh at Colchester General Hospital.
7. United Kingdom - Scotland was added as a country of recruitment.
15/07/2022: The following changes have been made:
1. The recruitment end date has been changed from 30/06/2022 to 31/12/2024.
2. The overall trial end date has been changed from 31/03/2027 to 31/12/2029.
3. The intention to publish date has been changed from 31/03/2028 to 01/01/2030.
20/09/2021: Internal review.
09/07/2020: The trial contact details have been made publicly visible.
28/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Prostate Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of male genital organs" to "Prostate cancer" following a request from the NIHR.
12/09/2018: Link to plain English summary added.
07/06/2018: Internal review
14/05/2018: Internal review.
