A study to assess the effects of enobosarm on early breast cancer

ISRCTN	ISRCTN12213700
DOI	https://doi.org/10.1186/ISRCTN12213700
EudraCT/CTIS number	2016-000543-13
Secondary identifying numbers	31856

Submission date: 23/01/2017
Registration date: 26/01/2017
Last edited: 09/01/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-enobosarm-for-women-with-early-breast-cancer-emerald

Contact information

Prof Carlo Palmeiri
Scientific

Department of Molecular and Clinical Cancer Medicine
Institute of Translational Medicine
Faculty of Health and Life Sciences
University of Liverpool
Sherrington Building
Ashton Street
Liverpool
L69 3GE
United Kingdom

Phone	+44 151 706 3616
Email	c.palmieri@liv.ac.uk

Ms Ediri O’Brien
Public

Cancer Research UK: Liverpool Cancer Trials Unit
Block C Waterhouse Building
1-3 Brownlow Street
University of Liverpool
Liverpool
L69 3GL
United Kingdom

Phone	+44 151 794 8209
Email	emeraldtrial@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 enobosarm in oestrogen receptor positive, androgen receptor positive early breast cancer
Study acronym	EMERALD
Study objectives	The aim of this study is to determine the effect of enobosarm, a selective androgen receptor modulator, using a "window of opportunity study" in women with early breast cancer.
Ethics approval(s)	North West – Haydock Research Ethics Committee, 28/12/2016, ref: 16/NW/0807
Health condition(s) or problem(s) studied	Specialty: Cancer, Primary sub-specialty: Breast Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasm of breast
Intervention	Current interventions as of 24/09/2018: Patients are screened, consented and then randomised onto the trial using the LCTUs TARDIS (Treatment Allocation RanDomIsation System) which for EMERALD uses randomly permuted blocks based on stratified lists to a ratio of 3:1 (treatment : standard of care). Treatment arm: Patients will take 9 mg of enobosarm capsules orally every day for 14 (+4) days, before pre-scheduled surgery/research core biopsy (within 24 hours of last dose). Patients will be followed up for 14 days after surgery/research core biopsy for adverse events. Blood (20 ml or about 4 teaspoons) will be taken at the Baseline Visit (Day 1) and the Tissue Collection Visit (Day 14). The sample from the core biopsy (FFPE block) will be requested to measure Ki67 at baseline and a sample (FFPE block) will be taken from the surgical specimen/research core biopsy specimen. Standard care arm: Patients will have their pre-scheduled surgery/research core biopsy as planned after 14 (+4) days. Blood (20 ml or about 4 teaspoons) will be taken at the Baseline Visit (Day 1) and the Tissue Collection Visit (Day 14). The sample from the core biopsy (FFPE block) will be requested to measure Ki67 at baseline and a sample (FFPE block) will be taken from the surgical specimen/research core biopsy specimen. Previous interventions: Patients are screened, consented and then randomised onto the trial using the LCTUs TARDIS (Treatment Allocation RanDomIsation System) which for EMERALD uses randomly permuted blocks based on stratified lists to a ratio of 3:1 (treatment : standard of care). Treatment arm: Patients will take 9mg of enobosarm capsules orally every day for 14(+4) days, before pre-scheduled surgery (within 24 hours of last dose). Patients will be followed up for 14 days after surgery for adverse events. Blood (20ml or about 4 teaspoons) will be taken at the baseline visit (Day 1), the mid-treatment visit (Day 7) and the surgery visit (Day 14). The sample from the core biopsy (FFPE block) will be requested to measure Ki67 at baseline and a sample (FFPE block) will be taken from the surgical specimen. Standard care arm: Patients will have their pre-scheduled surgery as planned after 14 (+4) days. Blood (20ml or about 4 teaspoons) will be taken at the baseline visit (Day 1), the mid-treatment visit (Day 7) and the surgery visit (Day 14). The sample from the core biopsy (FFPE block) will be requested to measure Ki67 at baseline and a sample (FFPE block) will be taken from the surgical specimen.
Intervention type	Other
Primary outcome measure	Current primary outcome measure as of 24/09/2018: Change in the proliferation marker Ki67 (% positive tumour cells) determined by tissue immunohistochemistry at baseline and 2 weeks. Previous primary outcome measure: Reduction in the proliferation marker Ki67 (% positive tumour cells) determined by tissue immunohistochemistry at baseline and 2 weeks.
Secondary outcome measures	Current secondary outcome measures as of 24/09/2018: 1. Amount of cleaved caspase 3 determined by tissue immunohistochemistry at baseline and two weeks 2. Expression of PSA, Gross Cystic Disease Fluid Proteins (GCDFP)-24 &-15; PgR, GREB1 by tissue immunohistochemistry at baseline and two weeks 3. Amount in serum levels of circulating steroidogenic hormones oestradiol, oestrone, oestrone sulfate, androstenedione, follicle stimulating hormone, luteinizing hormone, DHT, progesterone, sex hormone binding globulin (SHBG) and total testosterone in blood determined by blood assay at baseline and two weeks; free testosterone to be derived from SHBG and total testosterone 4. Amount in serum levels of PSA and steroidogenic hormones determined by blood assay at baseline and two weeks Previous secondary outcome measures: 1. Amount of cleaved caspase 3 determined by tissue immunohistochemistry at baseline and two weeks 2. Expression of PSA, Gross Cystic Disease Fluid Proteins (GCDFP)-24 &-15; PgR, GREB1 by tissue immunohistochemistry at baseline and two weeks 3. Amount in plasma levels of circulating steroidogenic hormones oestradiol, oestrone, oestrone sulfate, androstenedione, follicle stimulating hormone, luteinizing hormone, DHT, progesterone, sex hormone binding globulin (SHBG) and total testosterone in blood determined by blood assay at baseline and two weeks; free testosterone to be derived from SHBG and total testosterone 4. Amount in plasma levels of PSA and steroidogenic hormones determined by blood assay at baseline and two weeks
Overall study start date	11/12/2015
Completion date	31/05/2019

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target number of participants	Planned Sample Size: 147; UK Sample Size: 147
Key inclusion criteria	Current inclusion criteria as of 24/09/2018: 1. Females 16 years of age or older 2. Histologically confirmed ER positive breast cancer (Allred ≥3) 3. AnR positive breast cancer (defined as ≥10% nuclear AnR staining by immunohistochemistry) 4. Any HER2 status 5. Tumour measuring ≥14 mm in longest diameter by ultrasound (US) examination, MRI or mammogram 6. Postmenopausal as defined by one of the following criteria: 6.1. Women ≥55 years of age with an intact uterus and amenorrhoea ≥12 months at the time of diagnosis (or documented or current FSH and oestradiol levels within the postmenopausal range (as per local institutional/laboratory standard)) 6.2. Prior bilateral oophorectomy 6.3. Documented or current FSH and oestradiol levels within the postmenopausal range (as per local institutional/laboratory standard) in women aged <55 years or in women who have had a hysterectomy with intact ovaries 7. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 8. 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 ≤2.5 ULN and ALP ≤2.5 ULN 9. Acceptable risk of bleeding (e.g. bleeding diathesis, warfarin) as assessed by the PI (if the PI is unsure the CI will make the final decision) 10. Written informed consent 11. Able to comply with treatment and follow up Previous inclusion criteria: 1. Females 16 years of age or older 2. Histologically confirmed ER positive breast cancer (Allred ≥3) 3. AnR positive breast cancer (defined as ≥10% nuclear AnR staining by immunohistochemistry) 4. Any HER2 status 5. Tumour measuring ≥14mm in longest diameter by ultrasound (US) examination, MRI or mammogram 6. Postmenopausal as defined by one of the following criteria: 6.1. Amenorrhoea >12 months at the time of diagnosis and an intact uterus, with FSH and oestradiol in the postmenopausal ranges 6.2. Prior bilateral oophorectomy 6.3. FSH and oestradiol levels within the postmenopausal range (as per local practice) in women aged <55 years who have undergone hysterectomy 7. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 8. 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 ≤2.5 ULN and ALP ≤2.5 ULN 9. Acceptable risk of bleeding (e.g. bleeding diathesis, warfarin) as assessed by the PI (and where the PI is unsure the CI) 10. Written informed consent 11. Able to comply with treatment and follow up
Key exclusion criteria	Current exclusion criteria as of 24/09/2018: 1. Inoperable breast cancer 2. Males 3. Inflammatory tumours 4. Evidence of metastatic disease 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. Prior endocrine therapy of chemotherapy for breast cancer 7. Concomitant use (defined as use within 12 weeks prior to entry) of HRT or any other oestrogen-containing medication or supplement (including vaginal oestrogens and phytoestrogens) 8. Previous use of oestrogen implants within the last 12 weeks 9. Uncontrolled abnormalities of serum potassium, sodium, calcium or magnesium levels 10. Evidence of uncontrolled active infection 11. 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 12. Participation in a clinical trial of an IMP in the last 30 days Previous inclusion criteria: 1. Inoperable breast cancer 2. Inflammatory tumours 3. Evidence of metastatic disease 4. 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) 5. Evidence of bleeding diathesis 6. Prior endocrine therapy of chemotherapy for breast cancer 7. Concomitant use (defined as use within 12 weeks prior to entry) of HRT or any other oestrogen-containing medication or supplement (including vaginal oestrogens and phytoestrogens) 8. Previous use of oestrogen implants at ANY time 9. Uncontrolled abnormalities of serum potassium, sodium, calcium or magnesium levels 10. Evidence of uncontrolled active infection 11. 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 12. Participation in a clinical trial of an IMP in the last 30 days
Date of first enrolment	01/03/2017
Date of final enrolment	28/02/2019

Locations

Countries of recruitment

England
United Kingdom

Study participating centres

Cancer Research UK Liverpool Cancer Trials Unit

Block C, Waterhouse Building
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom

Royal Liverpool University Hospital

Prescot Street
Liverpool
L7 8XP
United Kingdom

University Hospital of South Manchester

Wythenshawe Hospital
Southmoor Road
Wythenshawe
Manchester
M23 9LT
United Kingdom

Macclesfield District General Hospital

Victoria Road
Macclesfield
SK10 3BL
United Kingdom

North Manchester General Hospital

Delaunays Road
Manchester
M8 5RB
United Kingdom

Clatterbridge Hospital

Wirral University Teaching Hospitals NHS Foundation Trust
Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom

Countess of Chester Hospital NHS Foundation Trust

Bache Hall
Chester Health Park
Chester
CH2 1UL
United Kingdom

Sponsor information

University of Liverpool
Hospital/treatment centre

1-3 Brownlow Street
Liverpool
L69 3BX
England
United Kingdom

"ROR"	https://ror.org/04xs57h96

Funders

Funder type

Charity

Cancer Research UK
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	30/11/2019
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned publication in a high-impact peer reviewed journal.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request following the process laid out on the LCTU website here or LCTU.org.uk > About the LCTU > Data Sharing.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol file	version 6.0	17/05/2021	09/01/2023	No	No
HRA research summary			28/06/2023	No	No

Additional files

ISRCTN12213700_Protocol_v6.0_17May2021.pdf

Editorial Notes

09/01/2023: Protocol file uploaded.
25/02/2018: The recruitment end date has been changed from 30/05/2018 to 28/02/2019.
24/09/2018: The following changes have been made:
1. Greg Gibson has been replaced by Ediri O’Brien as the public contact.
2. The interventions have been changed.
3. The primary outcome measures have been changed.
4. The secondary outcome measures have been changed.
5. The overall trial end date has been changed from 30/11/2018 to 31/05/2019.
6. The participant inclusion criteria have been changed.
7. The Target number of participants has been changed from 146 to 147.
8. The participant exclusion criteria have been changed.
9. University Hospital of South Manchester, Macclesfield District General Hospital, North Manchester General Hospital, Clatterbridge Hospital and Countess of Chester Hospital NHS Foundation Trust have been added to the trial centres.
16/10/2017: Cancer Help UK lay summary link added to plain English summary field
15/09/2017: Internal review.
06/06/2017: Internal review.