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 |
| IRAS number | 219463 |
| Secondary identifying numbers | CPMS 34511, IRAS 219463 |
- Submission date
- 08/01/2018
- Registration date
- 18/01/2018
- Last edited
- 12/09/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Contact information
Ms Shama Hassan
Public
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
| Study design | Randomised; Interventional; Design type: Treatment, Radiotherapy |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 hypothesis | 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 |
| Condition | 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. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | 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. |
| Secondary outcome measures | 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 2. Adherence to dose constraints is measured using collection of radiotherapy treatment doses/parameters at treatment 3. Acute bladder and bowel toxicity is measured using RTOG and CTC (v4.0) adverse event reporting at 3 months 4. Late toxicity is measured using RTOG and CTC (v4.0) adverse event reporting up to 10 years 5. Quality of life is measured using ALERT-B (Assessment of Late Effects of RadioTherapy - Bowel) screening tool, Gastrointestinal Symptom Rating Scale (GSRS), IIEF-5 Questionnaire (SHIM), International Prostate Symptom Score (IPSS), and Expanded Prostate Index Composite-26 (EPIC-26) Short Form questionnaire up to 10 years 6. Health economic endpoints are measured using EQ-5D up to 10 years |
| Overall study start date | 08/08/2016 |
| Overall study end date | 31/12/2029 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Male |
| Target number of participants | Planned Sample Size: 2229; UK Sample Size: 2229 |
| Total final enrolment | 2232 |
| Participant 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 <50ng/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) >6mm 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) |
| Participant 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 |
| Recruitment start date | 02/01/2018 |
| Recruitment end date | 30/08/2024 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
The Clatterbridge Cancer Centre
The Clatterbridge Cancer Centre Nhs Foundation Trust (Lead Site)
Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom
Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom
St. James's University Hospital
Leeds Teaching Hospitals NHS Trust
Beckett Street
Leeds
LS9 7TF
United Kingdom
Beckett Street
Leeds
LS9 7TF
United Kingdom
The Royal Marsden Hospita
The Royal Marsden Nhs Foundation Trust
Fulham Road
London
SW3 6JJ
United Kingdom
Fulham Road
London
SW3 6JJ
United Kingdom
Velindre Cancer Centre
Whitchurch Road
Cardiff
CF14 2TL
United Kingdom
Cardiff
CF14 2TL
United Kingdom
Lincoln County Hospital
United Lincolnshire Hospitals NHS Trust
Greetwell Road
Lincoln
LN2 4AX
United Kingdom
Greetwell Road
Lincoln
LN2 4AX
United Kingdom
Torbay Hospital
Torbay and South Devon NHS Foundation Trust
Hengrave House
Newton Road
Torquay
TQ2 7AA
United Kingdom
Hengrave House
Newton Road
Torquay
TQ2 7AA
United Kingdom
Queen Elizabeth Medical Centre
University Hospitals Birmingham NHS Foundation Trust
Edgbaston
Birmingham
B15 2TH
United Kingdom
Edgbaston
Birmingham
B15 2TH
United Kingdom
Musgrove Park Hospital
Taunton and Somerset NHS Foundation Trust
Taunton
TA1 5DA
United Kingdom
Taunton
TA1 5DA
United Kingdom
Norfolk and Norwich University Hospital
Norfolk and Norwich University Hospitals NHS Foundation Trust
Colney Lane
Colney
Norwich
NR4 7UY
United Kingdom
Colney Lane
Colney
Norwich
NR4 7UY
United Kingdom
Southampton General Hospital
University Hospital Southampton NHS Foundation Trust
Tremona Road
Southampton
SO16 6YD
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Freeman Hospital
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Freeman Road
High Heaton
Newcastle
NE7 7DN
United Kingdom
Freeman Road
High Heaton
Newcastle
NE7 7DN
United Kingdom
Addenbrookes hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Royal Free Hospital
Royal Free London NHS Foundation Trust
Pond Street
London
NW3 2QG
United Kingdom
Pond Street
London
NW3 2QG
United Kingdom
Royal Sussex County Hospital
Brighton and Sussex University Hospitals NHS Trust
Eastern Road
Brighton
BN2 5BE
United Kingdom
Eastern Road
Brighton
BN2 5BE
United Kingdom
Maidstone Hospital
Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom
Maidstone
ME16 9QQ
United Kingdom
Royal Surrey County Hospital
Royal Surrey County Hospital Nhs Foundation Trust
Egerton Road
Surrey
Guildford
GU2 7XX
United Kingdom
Egerton Road
Surrey
Guildford
GU2 7XX
United Kingdom
Ipswich Hospital
Heath Road
Ipswich
IP4 5PD
United Kingdom
Ipswich
IP4 5PD
United Kingdom
University College Hospital
University College London Hospitals NHS Foundation Trust
250 Euston Road
London
NW1 2PG
United Kingdom
250 Euston Road
London
NW1 2PG
United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Queen Elizabeth Hospital
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom
Sherwood Forest Hospitals NHS Foundation Trust
Kings Mill Hospital
Mansfield Road
Sutton-in-ashfield
NG17 4JL
United Kingdom
Mansfield Road
Sutton-in-ashfield
NG17 4JL
United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
Northern General Hospital
Herries Road
Sheffield
S5 7AU
United Kingdom
Herries Road
Sheffield
S5 7AU
United Kingdom
Highland Health Board
NHS Highland, Assynt House, Beechwood Park, Old Perth Road
Inverness
IV2 3BW
United Kingdom
Inverness
IV2 3BW
United Kingdom
NIHR CLAHRC North Thames
Barts Health NHS Trust
The Royal London Hospital
Whitechapel
London
E1 1BB
United Kingdom
The Royal London Hospital
Whitechapel
London
E1 1BB
United Kingdom
North Tees and Hartlepool NHS Foundation Trust
University Hospital of Hartlepool
Holdforth Road
Hartlepool
TS24 9AH
United Kingdom
Holdforth Road
Hartlepool
TS24 9AH
United Kingdom
South Tees Hospitals NHS Foundation Trust
James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom
Marton Road
Middlesbrough
TS4 3BW
United Kingdom
Cuh at Colchester General Hospital
Colchester General Hospital
Turner Road
Colchester
CO4 5JL
United Kingdom
Turner Road
Colchester
CO4 5JL
United Kingdom
Sponsor information
Institute Of Cancer Research
Research organisation
Research organisation
Royal Cancer Hospital
237 Fulham Road
London
SW3 6JB
United Kingdom
"ROR" |
https://ror.org/043jzw605 |
|---|
Funders
Funder type
Charity
Cancer Research UK
No information available
Results and Publications
| Intention to publish date | 01/01/2030 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The main trial results will be published in a peer-reviewed journal, on behalf of all collaborators. The manuscript will be prepared by a writing group, consisting of members of the TMG and selected participating clinicians. All participating clinicians will be acknowledged in the publication. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
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.
