Back to resultsA 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)
Primary Purpose
Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer
Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Giredestrant
Fulvestrant
Abemaciclib
Palbociclib
Ribociclib
LHRH Agonist
FoundationOne Liquid CDx Assay (F1LCDx)
Sponsored by
About this trial
This is an interventional treatment trial for Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer focused on measuring oral Selective Estrogen Receptor Degrader (SERD), CDK4/6 inhibitor (CDK4/6i), ESR1 mutation
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 archived tumor sample) Confirmed ESR1 mutation status (ESR1m vs. ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing Resistance to prior adjuvant endocrine therapy (ET). Prior use of neo/adjuvant CDK4/6i is allowed. No prior systemic anti-cancer therapy for advanced disease Measurable disease as defined per RECIST v.1.1 or non-measurable bone-only disease Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 For pre/perimenopausal women and for men: treatment with LHRH agonist therapy (as per local guidelines) for the duration of study treatment is required 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Giredestrant + Investigator's Choice of CDK4/6i
Fulvestrant + Investigator's Choice of CDK4/6i
Arm Description
Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup
PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), or death from any cause during the study.
PFS in the Full Analysis Set (FAS) Population
Secondary Outcome Measures
PFS in the ESR1 no-mutation-detected (ESR1nmd) Subgroup
Overall Survival (OS)
OS is defined as the time from randomization to death from any cause. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Confirmed Objective Response Rate (cORR)
The cORR is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart, as determined by the investigator according to RECIST v1.1. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Duration of Response (DOR)
DOR is defined as the time from the first occurrence of a documented objective response to PD, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Clinical Benefit Rate (CBR)
The CBR is defined as the percentage of participants with stable disease for at least (≥)24 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time to Chemotherapy
Time to chemotherapy is defined as the time from randomization until the start date of the first chemotherapy or death from any cause (whichever occurs first). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time to Confirmed Deterioration (TTCD) in Pain Severity
TTCD in pain severity is defined as the time from randomization to the first documentation of ≥2-point increase from baseline on the "worst pain" item score of the Brief Pain Inventory-Short Form (BPI-SF). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
TTCD in Pain Presence and Interference
TTCD in pain presence and interference is defined as the time from randomization to the first documentation of ≥10-point increase in pain score, as determined using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) questionnaire. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
TTCD in Physical Functioning
TTCD in physical functioning (PF) is defined as the time from randomization to the first documentation of ≥10-point decrease in PF score, as determined using the EORTC QLQ-C30 questionnaire. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
TTCD in Role Functioning
TTCD in role functioning (RF) is defined as the time from randomization to the first documentation of ≥10-point decrease in RF score, as determined using the EORTC QLQ-C30 questionnaire. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
TTCD in Global Health Status/Quality of Life
TTCD in in Global Health Status/Quality of Life (GHS/QoL) is defined as the time from randomization to the first documentation of ≥10-point decrease in GHS/QoL score, as determined using the EORTC QLQ-C30 questionnaire. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Incidence and Severity of Adverse Events
Incidence will be reported as the number of participants with at least one adverse event, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0).
Number of Participants with Vital Sign Abnormalities Over the Course of the Study
Vital signs include respiratory rate, pulse rate, systolic and diastolic blood pressure, and temperature.
Number of Participants with Clinical Laboratory Test Abnormalities for Hematology and Biochemistry Parameters Over the Course of the Study
Full Information
NCT ID
NCT06065748
First Posted
September 26, 2023
Last Updated
September 26, 2023
Sponsor
Hoffmann-La Roche
1. Study Identification
Unique Protocol Identification Number
NCT06065748
Brief Title
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)
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 31, 2023 (Anticipated)
Primary Completion Date
July 30, 2026 (Anticipated)
Study Completion Date
December 30, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer
Keywords
oral Selective Estrogen Receptor Degrader (SERD), CDK4/6 inhibitor (CDK4/6i), ESR1 mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1050 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Giredestrant + Investigator's Choice of CDK4/6i
Arm Type
Experimental
Arm Description
Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
Arm Title
Fulvestrant + Investigator's Choice of CDK4/6i
Arm Type
Active Comparator
Arm Description
Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.
Intervention Type
Drug
Intervention Name(s)
Giredestrant
Other Intervention Name(s)
RO7197597, RG6171, GDC-9545
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Abemaciclib
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Palbociclib
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ribociclib
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
LHRH Agonist
Intervention Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
FoundationOne Liquid CDx Assay (F1LCDx)
Other Intervention Name(s)
F1LCDx
Intervention Description
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 Measure Information:
Title
Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup
Description
PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), or death from any cause during the study.
Time Frame
From randomization to first occurrence of progressive disease (PD) or death (up to 5 years)
Title
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 Measure Information:
Title
PFS in the ESR1 no-mutation-detected (ESR1nmd) Subgroup
Time Frame
From randomization to first occurrence of PD or death (up to 5 years)
Title
Overall Survival (OS)
Description
OS is defined as the time from randomization to death from any cause. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time Frame
From randomization until death from any cause (up to 5 years)
Title
Confirmed Objective Response Rate (cORR)
Description
The cORR is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart, as determined by the investigator according to RECIST v1.1. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time Frame
From randomization until treatment discontinuation (up to 5 years)
Title
Duration of Response (DOR)
Description
DOR is defined as the time from the first occurrence of a documented objective response to PD, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time Frame
From the first occurrence of a documented objective response to PD or death (up to 5 years)
Title
Clinical Benefit Rate (CBR)
Description
The CBR is defined as the percentage of participants with stable disease for at least (≥)24 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time Frame
From randomization until treatment discontinuation (up to 5 years)
Title
Time to Chemotherapy
Description
Time to chemotherapy is defined as the time from randomization until the start date of the first chemotherapy or death from any cause (whichever occurs first). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time Frame
From randomization until the start of chemotherapy or death (up to 5 years)
Title
Time to Confirmed Deterioration (TTCD) in Pain Severity
Description
TTCD in pain severity is defined as the time from randomization to the first documentation of ≥2-point increase from baseline on the "worst pain" item score of the Brief Pain Inventory-Short Form (BPI-SF). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time Frame
From randomization until end of follow-up (up to 5 years)
Title
TTCD in Pain Presence and Interference
Description
TTCD in pain presence and interference is defined as the time from randomization to the first documentation of ≥10-point increase in pain score, as determined using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) questionnaire. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time Frame
From randomization until end of follow-up (up to 5 years)
Title
TTCD in Physical Functioning
Description
TTCD in physical functioning (PF) is defined as the time from randomization to the first documentation of ≥10-point decrease in PF score, as determined using the EORTC QLQ-C30 questionnaire. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time Frame
From randomization until end of follow-up (up to 5 years)
Title
TTCD in Role Functioning
Description
TTCD in role functioning (RF) is defined as the time from randomization to the first documentation of ≥10-point decrease in RF score, as determined using the EORTC QLQ-C30 questionnaire. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time Frame
From randomization until end of follow-up (up to 5 years)
Title
TTCD in Global Health Status/Quality of Life
Description
TTCD in in Global Health Status/Quality of Life (GHS/QoL) is defined as the time from randomization to the first documentation of ≥10-point decrease in GHS/QoL score, as determined using the EORTC QLQ-C30 questionnaire. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups.
Time Frame
From randomization until end of follow-up (up to 5 years)
Title
Incidence and Severity of Adverse Events
Description
Incidence will be reported as the number of participants with at least one adverse event, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0).
Time Frame
From Baseline until 28 days after the final dose of study treatment (up to 5 years)
Title
Number of Participants with Vital Sign Abnormalities Over the Course of the Study
Description
Vital signs include respiratory rate, pulse rate, systolic and diastolic blood pressure, and temperature.
Time Frame
From Baseline until 28 days after the final dose of study treatment (up to 5 years)
Title
Number of Participants with Clinical Laboratory Test Abnormalities for Hematology and Biochemistry Parameters Over the Course of the Study
Time Frame
From Baseline until 28 days after the final dose of study treatment (up to 5 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 archived tumor sample)
Confirmed ESR1 mutation status (ESR1m vs. ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing
Resistance to prior adjuvant endocrine therapy (ET). Prior use of neo/adjuvant CDK4/6i is allowed.
No prior systemic anti-cancer therapy for advanced disease
Measurable disease as defined per RECIST v.1.1 or non-measurable bone-only disease
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
For pre/perimenopausal women and for men: treatment with LHRH agonist therapy (as per local guidelines) for the duration of study treatment is required
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: CO44657 https://forpatients.roche.com/
Phone
888-662-6728 (U.S. Only)
Email
global-roche-genentech-trials@gene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).
For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).
Learn more about this trial
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)
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