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A Pre-operative Window Study of Letrozole Plus PR Agonist (Megestrol Acetate) Versus Letrozole Alone in Post-menopausal Patients With ER-positive Breast Cancer

NCT03306472 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 198

Last updated 2024-01-30

No results posted yet for this study

Summary

Around 75% of breast cancers are defined and driven by Oestrogen receptor alpha (ERα) transcriptional activity. Standard treatment is endocrine therapy however clinical outcomes vary considerably, and a proportion of women with early breast cancer driven by ERα transcriptional activity develop drug resistance, and relapse with incurable, metastatic disease.

Historically, PR-positivity was viewed as just a passive consequence of a functional oestrogen receptor, and PR was established as a biomarker of ER functionality in breast cancer. However, recent preclinical discoveries have provided an alternative explanation to the previous over-simplistic assumption, providing new insights into progestogen action and functional 'cross-talk' between ER and PR in breast cancer. In the presence of agonist ligands, progesterone-activated PR causes rapid sequestration of ERa chromatin binding sites in breast cancer cells, resulting in a unique gene expression program that is associated with a good clinical outcomes. This highlights a potential therapeutic opportunity.

The PIONEER trial will investigate the effect of combining megestrol acetate (a progesterone receptor agonist) and letrozole (an aromatase inhibitor) in post menopausal women with early breast cancer. This is a 'window of opportunity' study treating and observing patients in the two weeks prior to definitive surgery. Patients are randomised into one of three arms; one in which the patients receive Letrozole alone; one in which they will receive a combination of Letrozole and low dose Megestrol acetate and the third arm will receive Letrozole and high dose Megestrol acetate. This trial will be open to postmenopausal women with newly diagnosed, untreated ER-positive, HER2-negative, invasive primary breast cancer.

Conditions

Interventions

DRUG

Megestrol Acetate 40 MG

Progesterone Agonist

DRUG

Megestrol Acetate 160 MG

Progesterone Agonist

DRUG

Letrozole

Aromatase Inhibitor

Sponsors & Collaborators

  • Anticancer Fund, Belgium

    collaborator OTHER

  • Cambridge University Hospitals NHS Foundation Trust

    lead OTHER

Principal Investigators

  • Richard Baird, MA MBBS PhD FRCP · Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
FEMALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2017-07-20
Primary Completion
2022-10-31
Completion
2023-10-31
FDA Drug
Yes

Countries

  • United Kingdom

Study Locations

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03306472 on ClinicalTrials.gov