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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04576455
Recruitment Status : Active, not recruiting
First Posted : October 6, 2020
Last Update Posted : November 15, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE September 30, 2020
First Posted Date  ICMJE October 6, 2020
Last Update Posted Date November 15, 2021
Actual Study Start Date  ICMJE November 27, 2020
Estimated Primary Completion Date March 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 30, 2020)
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) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2021)
  • Overall Survival [ Time Frame: From randomization to death from any cause (up to 40 months) ]
  • 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) ]
    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.
  • 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) ]
  • 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) ]
    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).
  • 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) ]
  • 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) ]
  • 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) ]
    EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
    Vital signs include respiratory rate, pulse rate, systolic and diastolic blood pressure while the patient is in a seated position, and temperature.
  • 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) ]
  • 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) ]
  • Plasma Concentration of Giredestrant 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2020)
  • Overall Survival [ Time Frame: From randomization to death from any cause (up to 40 months) ]
  • 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) ]
    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.
  • 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) ]
  • 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) ]
    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).
  • 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) ]
  • 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) ]
  • 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) ]
    EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
    Vital signs include respiratory rate, pulse rate, systolic and diastolic blood pressure while the patient is in a seated position, and temperature.
  • 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) ]
  • 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) ]
  • 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) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Efficacy and Safety of Giredestrant Compared With Physician's Choice of Endocrine Monotherapy in Participants With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (acelERA Breast Cancer)
Official Title  ICMJE 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
Brief Summary This Phase II, randomized, open-label, multicenter study will evaluate the efficacy and safety of giredestrant 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 or metastatic setting.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
Intervention  ICMJE
  • Drug: Giredestrant
    Giredestrant is taken orally once per day on Days 1-28 of each 28-day cycle.
    Other Names:
    • GDC-9545
    • RO7197597
    • RG6171
  • Drug: Fulvestrant or an Aromatase Inhibitor (Physician's Choice)
    Physician's choice of endocrine monotherapy (fulvestrant or an aromatase inhibitor) is taken in accordance with the local prescribing information for the respective product.
  • Drug: LHRH Agonist
    Only premenopausal/perimenopausal participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist on Day 1 of each 28-day treatment cycle. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.
Study Arms  ICMJE
  • Experimental: Giredestrant
    Interventions:
    • Drug: Giredestrant
    • Drug: LHRH Agonist
  • Active Comparator: Physician's Choice of Endocrine Monotherapy
    The physician's choice of endocrine monotherapy will be limited to fulvestrant or an aromatase inhibitor.
    Interventions:
    • Drug: Fulvestrant or an Aromatase Inhibitor (Physician's Choice)
    • Drug: LHRH Agonist
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 11, 2021)
303
Original Estimated Enrollment  ICMJE
 (submitted: September 30, 2020)
300
Estimated Study Completion Date  ICMJE January 31, 2024
Estimated Primary Completion Date March 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Women who are postmenopausal or premenopausal/perimenopausal
  • For women who are premenopausal or perimenopausal and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy for the duration of study treatment
  • Locally advanced 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 or metastatic setting
  • 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 (ECOG) Performance Status 0-1
  • Adequate organ function

Exclusion Criteria:

  • Prior treatment with a selective estrogen receptor degrader (SERD), with the exception of fulvestrant, if fulvestrant treatment was terminated at least 28 days prior to randomization
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   China,   Germany,   Israel,   Korea, Republic of,   Poland,   Russian Federation,   Singapore,   South Africa,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04576455
Other Study ID Numbers  ICMJE WO42312
2020-001984-10 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

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 Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP