Condition category
Cancer
Date applied
04/06/2018
Date assigned
14/06/2018
Last edited
14/06/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Some women have an inheritable fault in their genetic code which increases their risk of developing ovarian cancer. Genes in which a fault may lie are BRCA1/ BRCA2/ RAD51C/ RAD51D/ BRIP1. Some women with a strong family history of ovarian cancer or breast and ovarian cancer may also be at increased risk. There is currently no screening programme for ovarian cancer available on the NHS. Therefore current practice is to offer women at increased risk, once they have completed their family, an operation to remove their fallopian tubes and ovaries. This procedure is called risk-reducing salpingo-oophorectomy. This is the best known way to prevent ovarian cancer in women at increased risk. However, in women who are premenopausal it leads to early menopause. Early menopause has serious health implications. It results in menopausal type symptoms (e.g. hot flushes, changes in mood, reduced sex drive), increased risk of osteoporosis (brittle bones), heart disease, stroke, dementia and sexual problems. Research suggests many ovarian cancers start in the fallopian tube. This has led to the proposal of an alternative strategy to prevent ovarian cancer. This involves having the operation in two stages. The first operation involves removing the fallopian tubes alone. This is called 'early salpingectomy’. The second operation removes the ovaries after natural menopause (average age 51 in the UK). This is called 'delayed oophorectomy’. The advantage of this two-stage alternative is that it offers some protection against ovarian cancer in young women whilst avoiding negative health consequences of early menopause.
The aim of the PROTECTOR study is to assess the impact of this two-stage alternative approach on sexual function. The study also evaluates the impact on quality of life, hormonal well-being, psychological well-being and overall satisfaction. Outcomes from this new approach are compared to the traditional approach of removal of both tubes and ovaries at the same operation. We also compare this to the well-being of women who do not have an operation.

Who can participate?
Women at increased risk of developing ovarian cance, who are aged 30 years and over and have not gone through the menopause.

What does the study involve?
Participants will be given the choice of which arm of the study they wish to be part of:
1. RRESDO (risk-reducing early salpingectomy and delayed oophorectomy): the new, two-stage operation (initial removal of tubes alone, followed by later removal of ovaries at a second operation after natural menopause or sooner if requested).
2. RRSO (risk-reducing salpingo-oophorectomy): removal of both tubes and ovaries at the same time. This is the current standard operation offered on the NHS to prevent ovarian cancer.
3. Controls: no operation involved.
Everyone will be required to complete questionnaires at the start of the study and annually. These ask about medical history, family history, quality of life, sexual function, cancer worry, psychological well-being and how satisfied individuals are with their decision.
All participants will also have a blood test at the start of the study and during follow up for a hormone called FSH. This will provide information on how the ovaries are functioning. Women who decide to have an operation to prevent ovarian cancer (either RRSO or RRESDO) will have a baseline ultrasound scan to look at the ovaries and a blood test for an ovarian cancer marker called CA125.
A small number of women from each study arm will be approached to take part in an optional interview. Interviews will explore views on acceptability, interest, factors influencing decision-making and willingness to undergo the new two-stage operation. Those who go on to have an operation (RRESDO/RRSO), will be contacted 1 year after their operation for a follow-up interview to discuss their satisfaction with the process and their general health and wellbeing.

What are the possible benefits and risks of participating?
Benefits include:
1. The opportunity of having a two staged operation (RRESDO) to prevent ovarian cancer. This is not currently routinely available outside the study. It involves removal of the tubes in the first step followed by removal of ovaries at a later date.
2. Removal of the tubes alone will provide some protection against developing ovarian cancer and also preserve ovarian function which will delay or avoid early menopause. This can prevent the adverse health consequences of early menopause.
3. Participants will be given the choice of deciding which arm of the study they wish to be a part of: RRESDO (new procedure), RRSO (current standard practice), or controls (no surgery).
4. Participants will be contributing to research into preventing ovarian cancer in women at increased risk. Results of this study will help us better understand the impact of the new two stage procedure. This will help develop future clinical care guidelines and plan future care pathways for women at increased risk of ovarian cancer.
Risks:
1. Although there is evidence to suggest removal of tubes alone provides some protection against developing ovarian cancer, the precise extent of this protection is unclear. There is the possibility of getting ovarian cancer despite removal of tubes.
2. It is unclear if a possible benefit of reduced breast cancer risk is lost by not removing ovaries before menopause.
3. The two-stage option (RRESDO) involves two operations instead of one (RRSO: removal of both tubes and ovaries). Each operation has potential complications. As there are two operations this may lead to more complications overall.
4. There is concern that not everyone having their tubes removed initially will go on to have their ovaries removed at a later date. This would mean that these women who don’t do so could still remain at an increased risk of developing ovarian cancer.

Where is the study run from?
Queen Mary University of London (UK)

When is the study starting and how long is it expected to run for?
July 2018 to July 2028

Who is funding the study?
Barts and the London Charity

Who is the main contact?
1. Dr Ranjit Manchanda (scientific)
r.manchanda@qmul.ac.uk
2. Dr Faiza Gaba (public)
f.gaba@qmul.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ranjit Manchanda

ORCID ID

http://orcid.org/0000-0003-3381-5057

Contact details

Barts Cancer Institute
Queen Mary University of London
Room 4
Basement
Old Anatomy Building
Charterhouse Square
London
EC1M 6BQ
United Kingdom
+44 (0)7979 884575
r.manchanda@qmul.ac.uk

Type

Public

Additional contact

Dr Faiza Gaba

ORCID ID

http://orcid.org/0000-0003-4081-6883

Contact details

Barts Cancer Institute
ECMC
Queen Mary University of London
Charterhouse Square
London
EC1M 6BQ
United Kingdom
+44 (0)20 7882 8491
f.gaba@qmul.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

IRAS project ID: 237992

Study information

Scientific title

Preventing Ovarian Cancer through early Excision of Tubes and late Ovarian Removal

Acronym

PROTECTOR

Study hypothesis

1. Early salpingectomy is non-inferior for sexual function compared to no surgery.
2. Early salpingectomy is superior for sexual function and non-inferior in terms of quality of life compared to the standard risk-reducing salpingo-oophorectomy.

Ethics approval

London - Bloomsbury Research Ethics Committee, 18/04/2018, ref: 18/LO/0555

Study design

Multicentre prospective three-armed cohort study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Condition

Prevention of ovarian cancer

Intervention

Participants who meet the eligibility criteria and who have been identified through various NHS outpatient clinics, GP-surgeries or who have self-referred to the study team, self-select which of the three study arms they wish to participate in: risk-reducing early salpingectomy and delayed oophorectomy (RRESDO); risk-reducing salpingo-oophorectomy (RRSO); controls (no surgery).

Baseline investigations
Participants enrolled into the two surgical arms (RRESDO/RRSO) have a CA125 and transvaginal ultrasound of the pelvis. Participants in all three arms have a baseline FSH as a measure of ovarian function and are required to complete interventional questionnaires that collect data on medical and reproductive history, socio-demographics, family history of cancers, endocrine symptoms, quality of life, satisfaction, psychological health and cancer risk perception and worry.

RRSO arm
Participants who have completed their family undergo risk reducing salpingo-oophorectomy and peritoneal washings. A strict histopathological SEE-FIM based protocol is followed and pathology samples are sent for central pathology review..

RRESDO arm
Participants who have completed their family undergo surgery in two stages. The first stage involves salpingectomy and peritoneal washings. The second stage involves oophorectomy and peritoneal washings once natural menopause has been reached (or sooner if requested). A strict histopathological SEE-FIM based protocol is followed and pathology samples are sent for central pathology review.

Control arm
Participants do not undergo surgery but undergo a blood test measuring FSH levels and are required to complete the interventional questionnaires.

Qualitative in-depth interviews
A small number of women from each of the three study arms are invited to one-to-one semi-structured in depth interviews to explore acceptability, interest, factors influencing decision making and willingness to undergo RRESDO. Women who elected to have surgery are followed up with another interview one year post salpingectomy/RRSO to explore satisfaction with the counselling process and the effects of surgery on health and wellbeing.

Follow up
All participants are followed up with annual questionnaires and FSH levels (annually after salpingectomy/control arm; 3 months after RRSO/delayed oophorectomy).

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

Sexual function measured using the Sexual Activity Questionnaire and Sexual Quality of Life 3D (SQOL-3D) questionnaire completed at baseline, 3 months post surgery and annually.

Secondary outcome measures

1. Endocrine function and menopause is measured using the FACT-ES questionnaire completed at baseline, 3 months post surgery, annually and FSH levels measured 3 months after surgery and annually (ealry salpingectomy/control arm)
2. Quality of life measured using the EQ5D-5L questionnaire completed at baseline, 3 months post surgery and annually
3. Satisfaction/regret is measured using the 5-item Decision Regret Scale (O'Connor, Ottawa 1996) and 1-item ('I am satisfied with the decision I have made' on a 5-point Likert scale from Madalinska et al, 2005) completed at baseline, 3 months post surgery and annually
4. Surgical morbidity measured by recording complications experienced by the participant 4 weeks after surgery during the post-surgical clinic review
5. Psychological health measured using the Hospital Anxiety and Depression Scale (HADS), assessing cancer worry using the 4-item scale from Lerman et al and measuring intrusive thoughts using the Impact of Events Scale (7 intrusive items, Horowitz et al, 1997) completed at baseline, 3 months post surgery and annually
6. Number of serous-tubal-intraepithelial-carcinoma (STIC)/invasive (tubal/ovarian/peritoneal/non-ovarian) cancers will be recorded following histopathology review by a central pathology review committee using the SEE-FIM protocol
7. Utility scores for early salpingectomy will be derived using the Sexual Quality of Life 3D (SQOL-3D) questionnaire
8. Cost-effectiveness (incremental cost effectiveness ratio per quality adjusted life years (ICER/QALY)) of early salpingectomy/delayed oophorectomy will be established via a cost utility analysis performed using a Markov model
9. A national register of women undergoing early salpingectomy will be created by collating the details of all participants who have undergone early salpingectomy as part of the trial

Overall trial start date

01/01/2017

Overall trial end date

01/07/2028

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Women at increased risk of ovarian cancer: BRCA1/BRCA2 mutation carriers; RAD51C/RAD51D/BRIP1 mutation carriers; strong family history of breast and ovarian cancer or ovarian cancer alone.
2. Premenopausal
3. Aged ≥30 years.
4. Completed family (for surgical arms)

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

1000

Participant exclusion criteria

1. Previous bilateral-salpingectomy or bilateral-oophorectomy.
2. Postmenopausal (amenorrhoea ≥1year (uterus in situ) / FSH >40).
3. Previous tubal/ovarian/peritoneal malignancy
4. <12 months post cancer treatment
5. Pregnancy
6. Clinical suspicion of tubal/ovarian cancer at baseline
7. Inability to provide informed consent

Recruitment start date

01/07/2018

Recruitment end date

01/07/2025

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Barts Health NHS Trust
W Smithfield
London
EC1A 7BE
United Kingdom

Trial participating centre

University College London Hospital Foundation Trust
235 Euston Rd, Fitzrovia
London
NW1 2BU
United Kingdom

Trial participating centre

Belfast Health & Social Care Trust
Belfast
BT9 7AB
United Kingdom

Trial participating centre

Cambridge University Hospitals NHS Foundation Trust
Hills Rd
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Manchester University NHS Foundation Trust
Southmoor Rd, Wythenshawe
Manchester
M23 9LT
United Kingdom

Trial participating centre

University Hospitals Birmingham NHS Foundation Trust
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Guy’s and St Thomas’ NHS Foundation Trust
Great Maze Pond
London
SE1 9RT
United Kingdom

Trial participating centre

The Royal Marsden NHS Foundation Trust
203 Fulham Rd, Chelsea
London
SW3 6JJ
United Kingdom

Trial participating centre

Imperial College Healthcare NHS Trust
The Bays S Wharf Rd Paddington
London
W2 1NY
United Kingdom

Trial participating centre

Aberdeen Royal Infirmary, NHS Grampian
Foresterhill
Aberdeen
AB25 2ZN
United Kingdom

Trial participating centre

Maidstone and Tunbridge Wells NHS Trust
Tonbridge Rd
Tunbridge Wells
TN2 4QJ
United Kingdom

Trial participating centre

Norfolk and Norwich University Hospitals
Colney Ln
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Gateshead Health NHS Foundation Trust
Queen Elizabeth Ave
Gateshead
NE9 6SX
United Kingdom

Trial participating centre

University Hospitals Bristol NHS Foundation Trust
Upper Maudlin St
Bristol
BS2 8HW
United Kingdom

Trial participating centre

Brighton and Sussex University Hospitals NHS Trust
Eastern Rd
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Sandwell and West Birmingham Hospitals
Dudley Rd
Birmingham
B18 7QH
United Kingdom

Trial participating centre

Oxford University Hospitals
Headley Way, Headington
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Ashford and St Peter’s Hospitals NHS Foundation Trust
Guildford Rd, Lyne
Chertsey
KT16 0PZ
United Kingdom

Trial participating centre

Cardiff and Vale NHS Trust
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

Northwick Park and St Mark's Hospitals
Watford Rd, Harrow
London
HA1 3UJ
United Kingdom

Trial participating centre

University Hospitals of Leicester NHS Trust
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Portsmouth Hospitals NHS Trust
Southwick Hill Rd, Cosham
Portsmouth
PO6 3LY
United Kingdom

Trial participating centre

Great Ormond Street Hospital NHS Trust
Great Ormond St
London
WC1N 3JH
United Kingdom

Trial participating centre

East Kent Hospitals University NHS Foundation Trust
Ethelbert Rd
Canterbury
CT1 3NG
United Kingdom

Trial participating centre

Ninewells Hospital, NHS Tayside
James Arrott Dr
Dundee
DD2 1SY
United Kingdom

Trial participating centre

Barking, Havering and Redbridge University Hospitals NHS Trust
Rom Valley Way
Romford
RM7 0AG
United Kingdom

Trial participating centre

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

Sponsor information

Organisation

Queen Mary University of London

Sponsor details

Joint Research Management Office
5 Walden Street
London
E1 2EF
United Kingdom
+44 (0)20 7882 7260
sponsorsrep@bartshealth.nhs.uk

Sponsor type

University/education

Website

http://www.qmul.ac.uk/

Funders

Funder type

Charity

Funder name

Barts and the London Charity

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Results of the research will be presented at scientific conferences and published in scientific journals. They will also be made available through cancer charities, patient support groups and the Queen Mary University of London website.

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

01/07/2029

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes