Description:
This Phase III, randomized, double-blind, placebo-controlled, multicenter study will evaluate
the efficacy and safety of giredestrant combined with palbociclib compared with letrozole
combined with palbociclib in patients with estrogen receptor (ER)-positive, human epidermal
growth factor receptor-2 (HER2)-negative locally advanced (recurrent or progressed) or
metastatic breast cancer.
Title
- Brief Title: A Study Evaluating the Efficacy and Safety of Giredestrant Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (persevERA Breast Cancer)
- Official Title: A Phase III Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of GDC-9545 Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Patients With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
BO41843
- SECONDARY ID:
2020-000119-66
- NCT ID:
NCT04546009
Conditions
- Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
Interventions
Drug | Synonyms | Arms |
---|
Giredestrant | GDC-9545, RO7197597, RG6171 | Giredestrant + Letrozole-matched Placebo + Palbociclib |
Giredestrant-matched Placebo | | Letrozole + Giredestrant-matched Placebo + Palbociclib |
Letrozole | | Letrozole + Giredestrant-matched Placebo + Palbociclib |
Letrozole-matched Placebo | | Giredestrant + Letrozole-matched Placebo + Palbociclib |
Palbociclib | | Giredestrant + Letrozole-matched Placebo + Palbociclib |
LHRH Agonist | | Giredestrant + Letrozole-matched Placebo + Palbociclib |
Purpose
This Phase III, randomized, double-blind, placebo-controlled, multicenter study will evaluate
the efficacy and safety of giredestrant combined with palbociclib compared with letrozole
combined with palbociclib in patients with estrogen receptor (ER)-positive, human epidermal
growth factor receptor-2 (HER2)-negative locally advanced (recurrent or progressed) or
metastatic breast cancer.
Trial Arms
Name | Type | Description | Interventions |
---|
Giredestrant + Letrozole-matched Placebo + Palbociclib | Experimental | | - Giredestrant
- Letrozole-matched Placebo
- Palbociclib
- LHRH Agonist
|
Letrozole + Giredestrant-matched Placebo + Palbociclib | Active Comparator | | - Giredestrant-matched Placebo
- Letrozole
- Palbociclib
- LHRH Agonist
|
Eligibility Criteria
Inclusion Criteria:
- For women who are premenopausal or perimenopausal and for men: treatment with approved
LHRH agonist therapy for the duration of study treatment
- Locally advanced (recurrent or progressed) or metastatic adenocarcinoma of the breast,
not amenable to treatment with curative intent
- Documented ER-positive tumor and HER2-negative tumor, assessed locally
- Patients who have bilateral breast cancers which are both ER-positive and
HER2-negative can be included in the study because the metastases are suitably
targeted by the study treatments. If patients have bilateral tumors which are of
different biomarker status, then proof of the ER and HER2 status of the metastases is
required for study entry
- No history of systemic anti-cancer therapy for locally advanced (recurrent or
progressed) or metastatic disease
- Disease recurrence from early-stage breast cancer after standard adjuvant endocrine
therapy meeting the protocol-defined criteria of having received at least 24 months of
treatment without disease progression during treatment and a disease-free interval
since the completion of treatment that was greater than 12 months
- Measurable disease as defined per RECIST v.1.1 or bone only disease which must have at
least one predominantly lytic bone lesion confirmed by CT or MRI which can be followed
- Eastern Cooperative Oncology Group Performance Status 0-1
- Adequate organ function
Exclusion Criteria:
- Disease recurrence during or within 12 months of completing prior neoadjuvant or
adjuvant treatment with an aromatase inhibitor (AI)
- Disease recurrence during or within 12 months of completing prior neoadjuvant or
adjuvant treatment with any CDK4/6 inhibitor
- Prior treatment with a selective estrogen receptor degrader (SERD)
- Prior treatment with tamoxifen is permitted, provided the patient did not experience
disease recurrence within the first 24 months of treatment with tamoxifen
- Treatment with any investigational therapy within 28 days prior to study treatment
- Advanced, symptomatic, visceral spread that is at risk of life-threatening
complications
- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or
leptomeningeal disease
- Active cardiac disease or history of cardiac dysfunction
- Pregnant or breastfeeding
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-Free Survival (PFS), as Determined by the Investigator According to RECIST v1.1 |
Time Frame: | From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 78 months) |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Overall Survival |
Time Frame: | From randomization to death from any cause (up to 78 months) |
Safety Issue: | |
Description: | |
Measure: | Objective Response Rate, as Determined by the Investigator According to RECIST v1.1 |
Time Frame: | From randomization until disease progression or death (up to 78 months) |
Safety Issue: | |
Description: | The objective response rate is defined as the percentage of participants with a complete response or partial response on two consecutive occasions at least (≥)4 weeks apart. |
Measure: | Duration of Response, as Determined by the Investigator According to RECIST v1.1 |
Time Frame: | From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to 78 months) |
Safety Issue: | |
Description: | |
Measure: | Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1 |
Time Frame: | From randomization until disease progression or death (up to 78 months) |
Safety Issue: | |
Description: | The clinical benefit rate is defined as the percentage of participants with stable disease for ≥24 weeks or a complete response or partial response. |
Measure: | Time to Deterioration in Pain Level, Defined as the Time to First Documented ≥2-Point Increase from Baseline in the 'Worst Pain' Item from the Brief Pain Inventory-Short Form (BPI-SF) Questionnaire |
Time Frame: | From Baseline until treatment discontinuation (up to 78 months) |
Safety Issue: | |
Description: | |
Measure: | Time to Deterioration in Pain Presence and Interference, Defined as the Time to First Documented ≥10-Point Increase from Baseline in the EORTC QLQ-C30 Linearly Transformed Pain Scale Score |
Time Frame: | From Baseline until treatment discontinuation (up to 78 months) |
Safety Issue: | |
Description: | EORTC QLQ-C30 = European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire |
Measure: | Time to Deterioration in Physical Functioning, Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed Physical Functioning Scale Score |
Time Frame: | From Baseline until treatment discontinuation (up to 78 months) |
Safety Issue: | |
Description: | |
Measure: | Time to Deterioration in Role Functioning, Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed Role Functioning Scale Score |
Time Frame: | From Baseline until treatment discontinuation (up to 78 months) |
Safety Issue: | |
Description: | |
Measure: | Time to Deterioration in Global Health Status and Quality of Life (GHS/QoL), Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed GHS/QoL Scale Score |
Time Frame: | From Baseline until treatment discontinuation (up to 78 months) |
Safety Issue: | |
Description: | |
Measure: | Number of Participants with Adverse Events, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) |
Time Frame: | From treatment initiation until 30 days after the final dose of study treatment (up to 78 months) |
Safety Issue: | |
Description: | |
Measure: | Number of Participants with Vital Sign Abnormalities Over the Course of the Study |
Time Frame: | Baseline, Days 1 and 15 of Cycles 1 and 2, and Day 1 of each cycle thereafter until treatment discontinuation (1 cycle is 28 days) |
Safety Issue: | |
Description: | Vital signs include respiratory rate, pulse rate, and systolic and diastolic blood pressure while the participant is in a seated position, and temperature. |
Measure: | Plasma Concentration of Giredestrant at Specified Timepoints |
Time Frame: | Days 1 and 15 of Cycle 1; Day 1 of Cycles 2, 4, 8, and 16 (1 cycle is 28 days) |
Safety Issue: | |
Description: | |
Measure: | Plasma Concentration of Palbociclib at Specified Timepoints |
Time Frame: | Days 1 and 15 of Cycle 1 (1 cycle is 28 days) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Hoffmann-La Roche |
Last Updated
August 20, 2021