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 |
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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
Plain English summary of protocol
Contact information
Public
Cambridge University Hospitals NHS Foundation Trust
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Phone | +44 (0)1233 348073 |
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Pioneer@addenbrookes.nhs.uk |
Study information
Study design | Randomised; Interventional; Design type: Treatment, Screening, Drug, Surgery |
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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 | 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 |
Study acronym | PIONEER |
Study objectives | 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(s) | Newcastle & North Tyneside 1 Research Ethics Committee, 24/05/2017, ref: 17/NE/0113 |
Health condition(s) or problem(s) studied | ER-positive breast cancer in post-menopausal patients |
Intervention | Patients 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 type | Drug |
Pharmaceutical study type(s) | |
Phase | Phase II |
Drug / device / biological / vaccine name(s) | Letrozole, megestrol acetate |
Primary outcome measure | 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 study start date | 14/02/2016 |
Completion date | 30/11/2022 |
Eligibility
Participant type(s) | Patient |
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Age group | Adult |
Sex | Female |
Target number of participants | Planned Sample Size: 189; UK Sample Size: 189 |
Key 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 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 criteria | 1. 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 enrolment | 01/07/2017 |
Date of final enrolment | 31/10/2021 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Hospital/treatment centre
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
Phone | +44 1223 348490 |
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r&denquiries@addenbrookes.nhs.uk | |
https://ror.org/04v54gj93 |
Funders
Funder type
Research organisation
No information available
Results and Publications
Intention to publish date | 30/11/2023 |
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Individual participant data (IPD) Intention to share | Yes |
IPD sharing plan summary | Other |
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 plan | The 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? |
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HRA research summary | 28/06/2023 | No | No | ||
Basic results | 15/10/2024 | 16/10/2024 | No | No |
Additional files
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.