Condition category
Cancer
Date applied
08/01/2018
Date assigned
18/01/2018
Last edited
14/05/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information

Type

Public

Primary contact

Ms Shama Hassan

ORCID ID

Contact details

The Institute of Cancer Research: Royal Cancer Hospital
123 Old Brompton Road
London
SW7 3RP
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

34511

Study information

Scientific title

A phase III randomised controlled trial of prostate and pelvis versus prostate alone radiotherapy with or without prostate boost

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

London-Chelsea Research Ethics Committee, 19/05/2017, ref: 17/LO/0731

Study design

Randomised; Interventional; Design type: Treatment, Radiotherapy

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 the contact details below to request a patient information sheet

Condition

Specialty: Cancer, Primary sub-specialty: Prostate Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of male genital organs

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

Phase

Drug names

Primary outcome measures

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 trial start date

08/08/2016

Overall trial end date

31/03/2027

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Male

Target number of participants

Planned Sample Size: 1952; UK Sample Size: 1952

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

30/06/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

The Clatterbridge Cancer Centre
The Clatterbridge Cancer Centre Nhs Foundation Trust (Lead Site) Clatterbridge Road Bebington
Wirral
CH63 4JY
United Kingdom

Trial participating centre

St. James's University Hospital
Leeds Teaching Hospitals NHS Trust Beckett Street
Leeds
LS9 7TF
United Kingdom

Trial participating centre

The Royal Marsden Hospita
The Royal Marsden Nhs Foundation Trust Fulham Road
London
SW3 6JJ
United Kingdom

Trial participating centre

Velindre Cancer Centre
Whitchurch Road
Cardiff
CF14 2TL
United Kingdom

Trial participating centre

Lincoln County Hospital
United Lincolnshire Hospitals NHS Trust Greetwell Road
Lincoln
LN2 4AX
United Kingdom

Trial participating centre

Torbay Hospital
Torbay and South Devon NHS Foundation Trust Hengrave House Newton Road
Torquay
TQ2 7AA
United Kingdom

Trial participating centre

Queen Elizabeth Medical Centre
University Hospitals Birmingham NHS Foundation Trust Edgbaston
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Musgrove Park Hospital
Taunton and Somerset NHS Foundation Trust
Taunton
TA1 5DA
United Kingdom

Trial participating centre

Norfolk and Norwich University Hospital
Norfolk and Norwich University Hospitals NHS Foundation Trust Colney Lane Colney
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Southampton General Hospital
University Hospital Southampton NHS Foundation Trust Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Freeman Hospital
The Newcastle Upon Tyne Hospitals NHS Foundation Trust Freeman Road High Heaton
Newcastle
NE7 7DN
United Kingdom

Trial participating centre

Addenbrookes hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Royal Free Hospital
Royal Free London NHS Foundation Trust Pond Street
London
NW3 2QG
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Brighton and Sussex University Hospitals NHS Trust Eastern Road
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Maidstone Hospital
Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom

Trial participating centre

Royal Surrey County Hospital
Royal Surrey County Hospital Nhs Foundation Trust Egerton Road Surrey
Guildford
GU2 7XX
United Kingdom

Trial participating centre

Ipswich Hospital
Heath Road
Ipswich
IP4 5PD
United Kingdom

Trial participating centre

University College Hospital
University College London Hospitals NHS Foundation Trust 250 Euston Road
London
NW1 2PG
United Kingdom

Sponsor information

Organisation

Institute Of Cancer Research

Sponsor details

Royal Cancer Hospital
237 Fulham Road
London
SW3 6JB
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

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 statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/03/2028

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

14/05/2018: Internal review.