A trial looking at progesterone to treat early breast cancer in premenopausal women
| ISRCTN | ISRCTN23662758 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN23662758 |
| EudraCT/CTIS number | 2017-001521-41 |
| IRAS number | 225455 |
| Secondary identifying numbers | CPMS 35420, IRAS 225455 |
- Submission date
- 04/09/2017
- Registration date
- 07/09/2017
- Last edited
- 11/10/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
See https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-electrocautery-ablation-to-prevent-lung-cancer-earl (added 08/01/2021)
Contact information
Miss Charlotte Rawcliffe
Public
Public
Cancer Research UK Liverpool Cancer Trials Unit
Block C, Waterhouse Building
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
| Phone | +44 (0)151 794 8167 / +44 (0)151 794 8932 |
|---|---|
| c.rawcliffe@liverpool.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug |
|---|---|
| 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 window of opportunity study to assess the biological effects of progesterone in premenopausal ER-positive, PgR-positive early breast cancer |
| Study acronym | PEARL |
| Study objectives | The aim of the study is to evaluate the effects of two-weeks preoperative therapy with micronised progesterone alongside tamoxifen in premenopausal women with ER-positive, PgR-positive early breast cancer. |
| Ethics approval(s) |
Approved 11/09/2017, North West - Greater Manchester South Research Ethics Committee (3rd Floor, Barlow House, 4 Minshull Street, Manchester, M1 3DZ, United Kingdom; +44 (0)207 104 8002; gmsouth.rec@hra.nhs.uk), ref: 17/NW/0460 |
| Health condition(s) or problem(s) studied | Specialty: Cancer, Primary sub-specialty: Breast Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasm of breast |
| Intervention | Patients are randomised 1:1 to either Tamoxifen plus micronised progesterone (therapeutic arm) or Tamoxifen alone (control arm). All participants take 100mg of Tamoxifen orally on Day 1, followed by 20mg of Tamoxifen orally, once daily from Day 2 until their scheduled breast surgery. Patients on the therapeutic arm also take 300mg micronised progesterone (Utrogestan) orally, once daily from Day 1 until their scheduled breast surgery. Surgery is scheduled for Day 14-18, so patients will receive study treatment for 14-18 days. Following surgery, patients return 28 days later and the following procedures will be carried out at this visit: 1. Haematology and biochemistry 2. Adverse event review and recording 3. Translational blood sample collection Adverse events will be reported until 28 days post treatment. |
| Intervention type | Other |
| Primary outcome measure | Changes in tumour cell proliferation will be measured using the Ki67 proliferation index at baseline (Day 0) and at surgery (Day 14-18). |
| Secondary outcome measures | 1. Changes in the pro-aptoptic marker cleaved caspase 3 are measured using tissue immunohistochemistry at baseline (Day 0) and at surgery (Day 14-18)* 2. Changes in ER, PgR, FoxA1, Cyclin D1, RANKL protein and mRNA expression are measured using tissue immunohistochemistry at baseline (Day 0) and at surgery (Day 14-18)* 3. Changes in circulating steroidogenic hormones are measured by analysis of blood samples at baseline and surgery (Day 14-18) 4. Pharmacokinetics of tamoxifen and N-desymethyltamoxifen (DMT) will be measured by mass spectrometry at Mid-treatment (Day 7) and surgery (Day 14-18) 5. Safety and tolerability of progesterone plus tamoxifen will be measured by the following – 5.1. Occurrence of grade 3+toxicity as classified by NCI-CTCAE v4.03 throughout the treatment period until 28 days post treatment. 5.2. Occurrence of adverse events throughout the treatment period until 28 days post treatment. 5.3. Occurrence of withdrawal from trial treatment due to toxicity throughout the treatment period until 28 days post treatment. 5.4. Experience of delay to scheduled surgery. |
| Overall study start date | 23/01/2017 |
| Completion date | 23/06/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Upper age limit | 49 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 112; UK Sample Size: 112 |
| Total final enrolment | 7 |
| Key inclusion criteria | 1. Women 16-49 years of age 2. Newly diagnosed histologically confirmed breast cancer 3. Premenopausal as defined by: gonadotrophin levels (luteinizing hormone and follicle stimulating hormone) and estradiol levels within the local laboratory’s reference range for premenopausal females 4. Ability to provide menstrual cycle information 5. ER positive (Allred ≥3) 6. PgR positive (Allred ≥3) 7. HER2 negative (IHC 1+ or 2+ and HER2/CEP17 ratio of <2) 8. Tumour measuring ≥14mm in longest diameter by ultrasound (US)/mammogram examination 9. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 10. Adequate bone marrow function defined by Hb≥10 g/dl, WBC≥3.0 x109 , PLT≥100 x109 /L. 11. Adequate renal function defined by a serum creatinine ≤1.5 x ULN. Adequate liver function defined by total bilirubin ≤ 1.5 ULN (patients with Gilbert’s syndrome exempted), either ALT or AST ≤1.5 ULN and ALP ≤1.5 ULN 12. Written informed consent, able to comply with treatment and follow-up 13. Currently using adequate contraception, and willing to continue use of this for the duration of the trial. Also willing to use a form of adequate contraception for one year following end of treatment (the type of contraception can be changed following the end of the trial). Adequate contraception is defined as either: 13.1. Total abstinence: When this is in line with the preferred and usual lifestyle of the subject. Periodic absence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. 13.2. Sterlisation: have had surgical tubal ligation at least six weeks before taking study treatment. 13.3. Male partner sterilization (with the appropriate postvasectomy documentation of the absence of sperm in the ejaculate). For female study subjects, the vasectomized male partner should be the sole partner for that patient. 13.4. Placement of a copper intrauterine device (IUD) 13.5. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository Note: Hormonal contraceptive methods (e.g. oral, injected and implanted) are not permitted. |
| Key exclusion criteria | 1. Inoperable breast cancer 2. Inflammatory tumours 3. Evidence of metastatic disease 4. Prior endocrine therapy or chemotherapy for breast cancer 5. Any history of invasive malignancy within 5 years of starting study treatment (other than adequately treated basal cell carcinoma or squamous cell carcinoma of the skin and cervical carcinoma in situ) 6. Concomitant use (defined as use within 12 weeks prior to entry) of OCP or any other oestrogen-containing medication or supplement 7. Concomitant use of any of the prohibited medications listed in Section 9.6.2 8. History of thromboembolic disease 9. Known carrier of genetic defects predisposing to thromboembolic disorders 10. Any medical condition that would prevent the use of low molecular weight heparin for venous thromboembolism prophylaxis 11. Uncontrolled abnormalities of serum potassium, sodium, calcium or magnesium levels 12. Evidence of bleeding diathesis 13. Evidence of uncontrolled active infection 14. Evidence of significant medical condition or laboratory finding which, in the opinion of the investigator, makes it undesirable for the patient to participate in the trial 15. Pregnant or lactating women |
| Date of first enrolment | 18/06/2018 |
| Date of final enrolment | 23/12/2018 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Royal Liverpool University Hospital
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Prescot Street
Liverpool
L7 8XP
United Kingdom
Prescot Street
Liverpool
L7 8XP
United Kingdom
Wythenshawe Hospital
University Hospital of South Manchester NHS Foundation Trust
Southmoor Road
Wythenshaw
Manchester
M23 9LT
United Kingdom
Southmoor Road
Wythenshaw
Manchester
M23 9LT
United Kingdom
New Cross Hospital
The Royal Wolverhampton NHS Trust
Wolverhampton Road
Heath Town
West Midlands
Wolverhampton
WV10 0QP
United Kingdom
Wolverhampton Road
Heath Town
West Midlands
Wolverhampton
WV10 0QP
United Kingdom
Arrowe Park Hospital
Wirral University Teaching Hospital NHS Foundation Trust
Arrowe Park Road
Wirral
Merseyide
Upton
CH49 5PE
United Kingdom
Arrowe Park Road
Wirral
Merseyide
Upton
CH49 5PE
United Kingdom
Macclesfield Distrcit General Hospital
East Cheshire NHS Trust
Victoria Road
Cheshire
Macclesfield
SK10 3BL
United Kingdom
Victoria Road
Cheshire
Macclesfield
SK10 3BL
United Kingdom
North Manchester General Hospital
Pennine Acute Hospitals NHS Trust
Delaunays Road
Crumpsall
Manchester
M8 5RB
United Kingdom
Delaunays Road
Crumpsall
Manchester
M8 5RB
United Kingdom
North Manchester General Hospital
Pennine Acute Hospitals NHS Trust
Delaunays Road
Crumpsall
Manchester
M8 5RB
United Kingdom
Delaunays Road
Crumpsall
Manchester
M8 5RB
United Kingdom
Guy’s Hospital
Guy’s and St Thomas’ NHS Foundation Trust
Great Maze Pond
London
SE1 9RT
United Kingdom
Great Maze Pond
London
SE1 9RT
United Kingdom
The Countess of Chester Health Park
Countess of Chester Hospital Foundation Trust
Cheshire
Chester
CH2 1UL
United Kingdom
Cheshire
Chester
CH2 1UL
United Kingdom
The Royal Bolton Hospital
Bolton NHS Foundation Trust
Minerva Road
Farnworth
Lancashire
Bolton
BL4 0JR
United Kingdom
Minerva Road
Farnworth
Lancashire
Bolton
BL4 0JR
United Kingdom
St James’s University Hospital
Derby Teaching Hospitals NHS Foundation Trust
Beckett Street
West Yorkshire
Leeds
LS9 7TF
United Kingdom
Beckett Street
West Yorkshire
Leeds
LS9 7TF
United Kingdom
Sponsor information
University of Liverpool
Hospital/treatment centre
Hospital/treatment centre
-
Liverpool
L69 3BX
England
United Kingdom
"ROR" |
https://ror.org/04xs57h96 |
|---|
Funders
Funder type
Government
Cancer Research UK
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/06/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Current publication and dissemination plan as of 11/10/2023: The Statistical Analysis Plan (SAP) cannot be executed reflecting the limitations resulting from the recruitment of 7 participants. The biological samples are unique and mimic the preclinical experiments. Although limited this provides the first data of this treatment in premenopausal women. The scientific group are a global leader in the field and the data will contribute to other evolving data. The investigators will seek to publish the study in a peer-reviewed journal once the additional work on the biological samples has been completed. In the meantime, summary results will be made available for trial registries. As the planned analysis outlined in the Protocol and SAP was not possible and therefore the Final Analysis Report (attached to the record) presents the baseline, compliance and safety data as line listings. Previous publication and dissemination plan: The main trial results will be published in the name of the trial in a peer-reviewed journal, on behalf of all collaborators. |
| IPD sharing plan | The datasets analysed during the conduct of the PEARL study will be available upon request from the trial Chief Investigator, Professor Carlo Palmieri, c.palmieri@liv.ac.uk |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Other unpublished results | Final Analysis Report version 1.0 |
06/10/2023 | 11/10/2023 | No | No |
Additional files
- ISRCTN23662758_Other unpublished results_v1.0_06Oct2023.pdf
- Final Analysis Report
Editorial Notes
11/10/2023: The following changes were made:
1. An unpublished results document has been uploaded as an additional file.
2. IRAS number added.
3. The total final enrolment was added.
4. The publication and dissemination plan was changed.
5. The Individual participant data (IPD) sharing plan and summary were added.
6. The Intention to publish date was changed from 23/06/2020 to 01/06/2024.
08/01/2021: Cancer Research UK plain English summary link added.
08/11/2019: Internal review.
05/08/2019: Internal review.
21/06/2019: Internal review.
05/04/2019: Internal review.
05/03/2019: Internal review.
07/06/2018: The recruitment start date was changed from 23/10/2017 to 18/06/2018.
06/06/2018: Internal review.
14/05/2018: Internal review.
16/01/2018: Internal review.
26/10/2017: Internal review.
