Condition category
Cancer
Date applied
02/05/2017
Date assigned
26/05/2017
Last edited
16/10/2017
Prospective/Retrospective
Prospectively 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

Mr Greig Dougall

ORCID ID

Contact details

Cambridge University Hospitals NHS Foundation Trust
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Additional identifiers

EudraCT number

2016-003752-79

ClinicalTrials.gov number

Protocol/serial number

33915

Study information

Scientific title

Randomised Phase II clinical trial PIONEER: A Pre-operative wIndOw study of letrozole plus PR agonist (Megestrol Acetate) versus letrozole aloNE in post-menopausal patients with ER-positive breast cancer

Acronym

PIONEER

Study hypothesis

The aim of this study is to investigate the effect of combining Megestrol Acetate (a progesterone receptor activator) and Letrozole (an anti-oestrogen, and standard endocrine therapy for post-menopausal women), in patients with newly diagnosed, untreated, ER-positive, HER2-negative, invasive primary breast cancer.

Ethics approval

Newcastle & North Tyneside 1 Research Ethics Committee, 24/05/2017, ref: 17/NE/0113

Study design

Randomised; Interventional; Design type: Treatment, Screening, Drug, Surgery

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: Breast Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasm of breast

Intervention

Patients will be randomised to one of three study arms.

Arm A: Participants receive oral Letrozole (2.5mg) alone daily for 15 days (this may be extended up to 19 days to accommodate the surgery date).
Arm B: Participants receive oral Letrozole 2.5mg plus Megestrol Acetate 40mg daily for 15 days (this may be extended up to 19 days to accommodate the surgery date).
Arm C: Participants receive oral Letrozole 2.5mg plus Megestrol Acetate 160mg daily for 15 days (this may be extended up to 19 days to accommodate the surgery date).

Intervention type

Drug

Phase

Phase II

Drug names

1. Letrozole
2. Megestrol Acetate

Primary outcome measures

Change in tumour proliferation is measured using Ki67 immuno-histochemical (IHC) assessment between pre-treatment (baseline) and post-treatment tumour samples (Day 15).

Secondary outcome measures

1. Change in tumour apoptosis is measured using Caspase 3 IHC assessment between pre-treatment (baseline) and post-treatment tumour samples (Day 15)
2. Changes in the expression of Androgen Receptor (AR) and Progesterone Receptor (PR) are measured using IHC assessment between pre-treatment (baseline) and post-treatment tumour samples (Day 15)
3. Change in proliferation by Aurora Kinase A (IHC) between baseline and Day 15 (+≤4 Days)
4. Change in tumour proliferation is also measured using Aurora Kinase A IHC assessment between pre-treatment (baseline) and post-treatment tumour samples (Day 15).
5. The absolute value of the Ki67 IHC assessment post-treatment (Day 15) is also recorded.
6. Safety of the trial treatments is assessed based on the incidence of serious adverse events and adverse events of all grades throughout the trial, grading is assessed using CTCAE criteria.

Exploratory Outcomes:
1. Transcription factor mapping of the Oestrogen Receptor (ER) will be assessed using ChIP-sequencing
2. The differences in response to treatments within the METABRIC-defined subtypes of ER-positive breast cancer will be assessed

Overall trial start date

14/02/2016

Overall trial end date

01/12/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Histologically confirmed breast adenocarcinoma
2. Postmenopausal women, defined as having experienced:
2.1. 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. ≥50 years, history of vasomotor symptoms) or
2.2. Six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or
2.3. Surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago.
3. Core biopsy confirmation of ER positive (Allred≥3) and HER2 negative invasive carcinoma on core biopsy, >=T1c, either cN0 or N+
4. Patients whose cancers have been deemed to be operable by the MDT
5. Surgery planned within the next 2-6 weeks
6. ECOG performance status of 0, 1 or 2
7. Adequate Liver, Renal and Bone marrow function, defined as:
7.1. Adequate liver function where bilirubin is ≤1.5 x ULN
7.2. Adequate renal function with estimated creatinine clearance of ≥60 ml/min
7.3. Adequate bone marrow function with ANC ≥1.0 x 109/L and Platelet count ≥100 x 109/L
8. Written informed consent to participate in the trial and to donation of tissue

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 189; UK Sample Size: 189

Participant exclusion criteria

1. History of hormone replacement therapy in the last 6 months
2. Previous treatment with tamoxifen or an aromatase inhibitor in the last six months
3. Known hypersensitivity or contraindications to aromatase inhibitors or megestrol acetate
4. Known allergy to lactose
5. Known to have a progestogen-containing intrauterine system in situ, unless removed prior to randomisation
6. Known metastatic disease on presentation
7. Recurrent breast cancer (patients with a new primary invasive breast cancer will be eligible to participate)
8. Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
9. Treatment with an investigational drug within 4 weeks before randomization
10. Inability to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the trial medication
11. Inability to give informed consent

Recruitment start date

01/07/2017

Recruitment end date

01/12/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cambridge University Hospitals NHS Foundation Trust
Addenbrooke’s Hospital Cambridge Biomedical Campus Hills Road
Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust

Sponsor details

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 1223 348490
r&denquiries@addenbrookes.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Research organisation

Funder name

Het Anti-Kankerfonds - Le Fonds Anti-Cancer

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal, with intent to have published by December 2019. Interim presentation of results in 2018/9 at local and international oncology meetings.

IPD Sharing statement:
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Intention to publish date

31/12/2019

Participant level data

Other

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

16/10/2017: Internal review. 11/08/2017: Internal review. 06/06/2017: Internal review.