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 |
| ClinicalTrials.gov (NCT) | NCT03306472 |
| Clinical Trials Information System (CTIS) | 2016-003752-79 |
| Protocol serial number | 33915 |
| Sponsor | Cambridge University Hospitals NHS Foundation Trust |
| Funder | Het Anti-Kankerfonds - Le Fonds Anti-Cancer |
- 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 |
|---|---|
| Pioneer@addenbrookes.nhs.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised; Interventional; Design type: Treatment, Screening, Drug, Surgery |
| Secondary study design | Randomised controlled trial |
| Study type | Participant 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 |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Letrozole, megestrol acetate |
| Primary outcome measure(s) |
Change in tumour proliferation is measured using Ki67 immuno-histochemical (IHC) assessment between pre-treatment (baseline) and post-treatment tumour samples (Day 15). |
| Key secondary outcome measure(s) |
1. Change in tumour apoptosis is measured using Caspase 3 IHC assessment between pre-treatment (baseline) and post-treatment tumour samples (Day 15) |
| Completion date | 30/11/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target sample size at registration | 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
- United Kingdom
- England
Study participating centre
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Other |
| 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? |
|---|---|---|---|---|---|
| Basic results | 15/10/2024 | 16/10/2024 | No | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Additional files
- ISRCTN15621797 PIONEER Basic results.pdf
- Basic results
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.
