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A Study Evaluating the Efficacy and Safety of GDC-9545 Compared With Physician's Choice of Endocrine Monotherapy in Participants With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

NCT04576455

Description:

This Phase II, randomized, open-label, multicenter study will evaluate the efficacy and safety of GDC-9545 compared with physician's choice of endocrine monotherapy in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have received one or two prior lines of systemic therapy in the locally advanced (recurrent or progressed) or metastatic setting.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Efficacy and Safety of GDC-9545 Compared With Physician's Choice of Endocrine Monotherapy in Participants With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
  • Official Title: A Phase II, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of GDC-9545 Compared With Physician's Choice of Endocrine Monotherapy in Patients With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: WO42312
  • SECONDARY ID: 2020-001984-10
  • NCT ID: NCT04576455

Conditions

  • Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer

Interventions

DrugSynonymsArms
GDC-9545RG6171GDC-9545
Fulvestrant or an Aromatase Inhibitor (Physician's Choice)Physician's Choice of Endocrine Monotherapy
LHRH AgonistGDC-9545

Purpose

This Phase II, randomized, open-label, multicenter study will evaluate the efficacy and safety of GDC-9545 compared with physician's choice of endocrine monotherapy in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have received one or two prior lines of systemic therapy in the locally advanced (recurrent or progressed) or metastatic setting.

Trial Arms

NameTypeDescriptionInterventions
GDC-9545Experimental
  • GDC-9545
  • LHRH Agonist
Physician's Choice of Endocrine MonotherapyActive ComparatorThe physician's choice of endocrine monotherapy will be limited to fulvestrant or an aromatase inhibitor.
  • Fulvestrant or an Aromatase Inhibitor (Physician's Choice)
  • 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

          -  Disease progression after treatment with one or two lines of systemic therapy (but not
             more than one prior targeted therapy) in the locally advanced (recurrent or
             progressed) or metastatic setting

          -  Measurable disease as defined per RECIST v.1.1

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          -  Adequate organ function

        Exclusion Criteria:

          -  Prior treatment with a selective estrogen receptor degrader (SERD), with the exception
             of fulvestrant

          -  Treatment with any investigational therapy within 28 days prior to randomization

          -  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, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time Frame:From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 40 months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:From randomization to death from any cause (up to 40 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 40 months)
Safety Issue:
Description:The objective response rate 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.
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 40 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 40 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 (CR) or partial response (PR).
Measure:Investigator-Assessed Progression-Free Survival, in Subgroups Categorized by ESR1 Mutation Status
Time Frame:From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 40 months)
Safety Issue:
Description:
Measure:Time to Deterioration in Pain Severity, 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 40 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 40 months)
Safety Issue:
Description:EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30
Measure:Time to Deterioration in Physical Functioning (PF), Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed PF Scale Score
Time Frame:From Baseline until treatment discontinuation (up to 40 months)
Safety Issue:
Description:
Measure:Time to Deterioration in Role Functioning (RF), Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed RF Scale Score
Time Frame:From Baseline until treatment discontinuation (up to 40 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 40 months)
Safety Issue:
Description:
Measure:Number of Participants with Adverse Events, Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Time Frame:From Baseline until 30 days after final dose of study drug (up to 40 months)
Safety Issue:
Description:
Measure:Number of Participants with Vital Sign Abnormalities Over the Course of the Study
Time Frame:Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to 40 months)
Safety Issue:
Description:Vital signs include respiratory rate, pulse rate, systolic and diastolic blood pressure while the patient is in a seated position, and temperature.
Measure:Number of Participants with Clinical Laboratory Test Abnormalities for Hematology Parameters Over the Course of the Study
Time Frame:Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to 40 months)
Safety Issue:
Description:
Measure:Number of Participants with Clinical Laboratory Test Abnormalities for Biochemistry Parameters Over the Course of the Study
Time Frame:Assessed at Baseline and predose on Day 1 of every cycle (1 cycle is 28 days) until 30 days after the final dose of study drug (up to 40 months)
Safety Issue:
Description:
Measure:Plasma Concentration of GDC-9545 at Specified Timepoints
Time Frame:Predose and postdose on Day 1 of Cycles 1 and 2, predose on Day 1 of Cycles 3, 5, 7, 9, 11, 13, and 15 (1 cycle is 28 days), and 30 days after final dose of study drug (up to 40 months)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

October 8, 2020