Description:
This Phase III, randomized, double-blind, placebo-controlled, multicenter study will evaluate
the efficacy and safety of GDC-9545 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 GDC-9545 Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic 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 |
|---|
| GDC-9545 | RG6171 | GDC-9545 + Letrozole-matched Placebo + Palbociclib |
| GDC-9545-matched Placebo | | Letrozole + GDC-9545-matched Placebo + Palbociclib |
| Letrozole | | Letrozole + GDC-9545-matched Placebo + Palbociclib |
| Letrozole-matched Placebo | | GDC-9545 + Letrozole-matched Placebo + Palbociclib |
| Palbociclib | | GDC-9545 + Letrozole-matched Placebo + Palbociclib |
| LHRH Agonist | | GDC-9545 + Letrozole-matched Placebo + Palbociclib |
Purpose
This Phase III, randomized, double-blind, placebo-controlled, multicenter study will evaluate
the efficacy and safety of GDC-9545 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 |
|---|
| GDC-9545 + Letrozole-matched Placebo + Palbociclib | Experimental | | - GDC-9545
- Letrozole-matched Placebo
- Palbociclib
- LHRH Agonist
|
| Letrozole + GDC-9545-matched Placebo + Palbociclib | Active Comparator | | - GDC-9545-matched Placebo
- Letrozole
- Palbociclib
- LHRH Agonist
|
Eligibility Criteria
Inclusion Criteria:
- For women who are premenopausal or perimenopausal or 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
- No history of systemic anti-cancer therapy for locally advanced (recurrent or
progressed) or metastatic disease
- Measurable disease as defined per RECIST v.1.1
- 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 GDC-9545 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: | Not yet recruiting |
| Lead Sponsor: | Hoffmann-La Roche |
Last Updated
September 8, 2020
