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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

NCT04546009

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.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

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

DrugSynonymsArms
GDC-9545RG6171GDC-9545 + Letrozole-matched Placebo + Palbociclib
GDC-9545-matched PlaceboLetrozole + GDC-9545-matched Placebo + Palbociclib
LetrozoleLetrozole + GDC-9545-matched Placebo + Palbociclib
Letrozole-matched PlaceboGDC-9545 + Letrozole-matched Placebo + Palbociclib
PalbociclibGDC-9545 + Letrozole-matched Placebo + Palbociclib
LHRH AgonistGDC-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

NameTypeDescriptionInterventions
GDC-9545 + Letrozole-matched Placebo + PalbociclibExperimental
  • GDC-9545
  • Letrozole-matched Placebo
  • Palbociclib
  • LHRH Agonist
Letrozole + GDC-9545-matched Placebo + PalbociclibActive 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