Recruiting NCT06065748

A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer)

Phase III Interventional Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Giredestrant, Fulvestrant, Abemaciclib, Palbociclib.
Who it may be relevant to: Registry conditions: Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Austria, Belgium +32
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Phase III Randomized, Open-Label Study Evaluating Efficacy and Safety of Giredestrant Compared With Fulvestrant, Both Combined With a CDK4/6 Inhibitor, in Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer With Resistance to Prior Adjuvant Endocrine Therapy

Overview

This is a Phase III, randomized, open-label multicenter study that will evaluate the efficacy and safety of giredestrant compared with fulvestrant, both in combination with the investigator's choice of a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib), in participants with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who have developed resistance to adjuvant endocrine therapy.

Interventions

Drug Giredestrant
Giredestrant 30 milligrams (mg) orally (PO) once a day (QD) on Days 1-28 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity.
Drug Fulvestrant
Fulvestrant 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle until PD or unacceptable toxicity.
Drug Abemaciclib
If chosen by the investigator as the CDK4/6i, participants will receive abemaciclib 150 mg PO twice per day (BID) on Days 1-28 of each 28-day cycle until PD or unacceptable toxicity.
Drug Palbociclib
If chosen by the investigator as the CDK4/6i, participants will receive palbociclib 125 mg PO QD on Days 1-21 of each 28-day cycle until PD or unacceptable toxicity.
Drug Ribociclib
If chosen by the investigator as the CDK4/6i, participants will receive ribociclib 600 mg PO QD on Days 1-21 of each 28-day cycle until PD or unacceptable toxicity.
Drug LHRH Agonist
Only pre/perimenopausal female participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer on Day 1 of each 28-day treatment cycle.
Diagnostic test FoundationOne Liquid CDx Assay (F1LCDx)
F1LCDx is a next-generation sequencing (NGS)-based in vitro diagnostic test that detects and analyses genomic alterations in circulating cell-free DNA (cfDNA) isolated from plasma derived from the anti-coagulated peripheral whole blood of cancer patients. It will be used to determine the eligibility of participants requiring confirmation of ESR1 mutation status (mutation detected \[ESR1m\] vs. no mutation detected \[ESR1nmd\]).

Primary outcome measures

Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup [Time frame: From randomization to first occurrence of progressive disease (PD) or death (up to 5 years)]
PFS in the Full Analysis Set (FAS) Population [Time frame: From randomization to first occurrence of PD or death (up to 5 years)]

Secondary outcome measures (12)

PFS in the ESR1 no-mutation-detected (ESR1nmd) Subgroup [Time frame: From randomization to first occurrence of PD or death (up to 5 years)]
Overall Survival (OS) [Time frame: From randomization until death from any cause (up to 5 years)]
Confirmed Objective Response Rate (cORR) [Time frame: From randomization until treatment discontinuation (up to 5 years)]
Duration of Response (DOR) [Time frame: From the first occurrence of a documented objective response to PD or death (up to 5 years)]
Clinical Benefit Rate (CBR) [Time frame: From randomization until treatment discontinuation (up to 5 years)]
Time to Chemotherapy [Time frame: From randomization until the start of chemotherapy or death (up to 5 years)]
Time to Confirmed Deterioration (TTCD) in Pain Severity [Time frame: From randomization until end of follow-up (up to 5 years)]
TTCD in Pain Presence and Interference [Time frame: From randomization until end of follow-up (up to 5 years)]
TTCD in Physical Functioning [Time frame: From randomization until end of follow-up (up to 5 years)]
TTCD in Role Functioning [Time frame: From randomization until end of follow-up (up to 5 years)]
TTCD in Global Health Status/Quality of Life [Time frame: From randomization until end of follow-up (up to 5 years)]
Incidence and Severity of Adverse Events [Time frame: From Baseline until 28 days after the final dose of study treatment (up to 5 years)]

Eligibility criteria

Inclusion criteria

Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
Documented estrogen receptor-positive (ER+), HER2-negative (HER2-) tumor assessed locally on the most recent tumor biopsy (or an archived tumor sample if a recent tumor sample is not available for testing)
Confirmed ESR1 mutation status (ESR1m versus ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing
Resistance to prior adjuvant endocrine therapy (ET), which is defined as having relapsed with prior standard adjuvant ET, on-treatment after >/=12 months or off-treatment within 12 months of completion. Prior use of adjuvant CDK4/6i is allowed (if relapse occurred >/=12 months since completion).
No prior systemic anti-cancer therapy for advanced disease
Measurable disease as defined per RECIST v.1.1 or non-measurable (including bone-only) disease
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
For pre/perimenopausal women and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy (as per local guidelines) for the duration of study treatment

Exclusion criteria

Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer
Prior treatment with another SERD (e.g., fulvestrant, oral SERDs) or novel ER-targeting agents
Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
Active cardiac disease or history of cardiac dysfunction
Clinically significant history of liver disease

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Open label
Primary purpose: Treatment