A pre-surgery trial looking at the effect of combining megestrol acetate with letrozole or letrozole alone for postmenopausal patients with early, oestrogen receptor positive breast cancer

ISRCTN ISRCTN15621797
DOI https://doi.org/10.1186/ISRCTN15621797
EudraCT/CTIS number 2016-003752-79
ClinicalTrials.gov number NCT03306472
Secondary identifying numbers 33915
Submission date
02/05/2017
Registration date
26/05/2017
Last edited
16/10/2024
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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-megestrol-acetate-and-letrozole-for-women-with-breast-cancer-pioneer

Contact information

Mr Angels Kateb
Public

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

Phone +44 (0)1233 348073
Email Pioneer@addenbrookes.nhs.uk

Study information

Study designRandomised; Interventional; Design type: Treatment, Screening, Drug, Surgery
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleRandomised 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
Study acronymPIONEER
Study objectivesThe 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(s)Newcastle & North Tyneside 1 Research Ethics Committee, 24/05/2017, ref: 17/NE/0113
Health condition(s) or problem(s) studiedER-positive breast cancer in post-menopausal patients
InterventionPatients will be randomised to one of three study arms.

Arm A: Participants receive oral letrozole (2.5 mg) 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 40 mg 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 typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Letrozole, megestrol acetate
Primary outcome measureChange in tumour proliferation is measured using Ki67 immuno-histochemical (IHC) assessment between pre-treatment (baseline) and post-treatment tumour samples (Day 15).
Secondary outcome measures1. 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 study start date14/02/2016
Completion date30/11/2022

Eligibility

Participant type(s)Patient
Age groupAdult
SexFemale
Target number of participantsPlanned Sample Size: 189; UK Sample Size: 189
Key inclusion criteria1. 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 10(9)/L and Platelet count ≥100 x 10(9)/L
8. Written informed consent to participate in the trial and to donation of tissue
Key exclusion criteria1. History of hormone replacement therapy in the last 6 months
2. Previous treatment with tamoxifen or an aromatase inhibitor in the last 6 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
Date of first enrolment01/07/2017
Date of final enrolment31/10/2021

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

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

Sponsor information

Cambridge University Hospitals NHS Foundation Trust
Hospital/treatment centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

Phone +44 1223 348490
Email r&denquiries@addenbrookes.nhs.uk
ROR logo "ROR" https://ror.org/04v54gj93

Funders

Funder type

Research organisation

Het Anti-Kankerfonds - Le Fonds Anti-Cancer

No information available

Results and Publications

Intention to publish date30/11/2023
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryOther
Publication and dissemination planPlanned 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 planThe datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
HRA research summary 28/06/2023 No No
Basic results 15/10/2024 16/10/2024 No No

Additional files

ISRCTN15621797 PIONEER Basic results.pdf

Editorial Notes

16/10/2024: The basic results have been uploaded as an additional file.
01/02/2021: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Breast Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasm of breast" to "ER-positive breast cancer in post-menopausal women" following a request from the NIHR.
20/10/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/12/2018 to 31/10/2021.
2. The overall end date was changed from 01/12/2019 to 30/11/2022.
3. The intention to publish date was changed from 31/12/2019 to 30/11/2023.
20/08/2020: The primary contact was changed.
16/01/2020: ClinicalTrials.gov number added.
16/01/2018: Cancer Help UK lay summary link added to plain English summary field.
16/10/2017: Internal review.
11/08/2017: Internal review.
06/06/2017: Internal review.