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)
- Conditions
- Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT04576455
- Lead Sponsor
- Hoffmann-La Roche
- 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 available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 303
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Giredestrant Giredestrant - Giredestrant LHRH Agonist - Physician Choice of Endocrine Monotherapy Fulvestrant or an Aromatase Inhibitor (Physician Choice) The physician choice of endocrine monotherapy will be limited to fulvestrant or an aromatase inhibitor. Physician Choice of Endocrine Monotherapy LHRH Agonist The physician choice of endocrine monotherapy will be limited to fulvestrant or an aromatase inhibitor.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (duration of follow-up, median [range]: 7.9 [0.0-14.1] months) PFS was defined as the Kaplan-Meier estimate of time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Kaplan-Meier methodology was used to estimate median PFS. The 95% confidence interval for the median was computed using the method of Brookmeyer and Crowley. Participants without the occurrence of disease progression or death as of the clinical cutoff were censored at the time of the last tumor assessment prior to the clinical cutoff or at the time of randomization plus 1 day for those without post-baseline assessment.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) From randomization to death from any cause (duration of follow-up, median [range]: 34.6 [0.0-41.8] months) Overall survival (OS) is defined as the Kaplan-Meier estimate of time from randomization to death from any cause. Kaplan-Meier methodology was used to estimate median OS. The 95% confidence interval for the median was computed using the method of Brookmeyer and Crowley. Analysis strata are: Site of disease, Prior treatment with CDK4/6 inhibitor and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression. Data for participants who were alive at the time of the analysis data cutoff were censored at the last date they were known to be alive. Data from participants without postbaseline information were censored at the date of randomization plus 1 day.
Objective Response Rate, as Determined by the Investigator According to RECIST v1.1 From randomization until disease progression or death (up to approximately 15 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. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Duration of Response (DOR), as Determined by the Investigator According to RECIST v1.1 From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 15 months) DOR is defined as the Kaplan-Meier estimate of time from the first occurrence of a documented objective response to disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first). Objective response rate is defined as the percentage of participants with a CR or PR on two consecutive occasions at least 4 weeks apart. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.
Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1 From randomization until disease progression or death (up to approximately 15 months) The clinical benefit rate is defined as the percentage of participants with stable disease for ≥24 weeks or a CR or PR. Per RECIST v1.1, CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Investigator-Assessed PFS, in Subgroups Categorized by Estrogen Receptor (ESR1) Mutation Status From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (duration of follow-up, median [range]: 7.9 [0.0-14.1] months) PFS was defined as the Kaplan-Meier estimate of time from randomization to the first occurrence of disease progression determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first). Disease progression was defined as ≥20% increase in in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Investigator-assessed PFS was analyzed in subgroups categorized by baseline ESR1 mutation status (i.e., with or without ESR1 mutation at baseline) from plasma circulating tumor deoxyribonucleic acid (ctDNA). Participants without the occurrence of disease progression or death as of the clinical cutoff were censored at the time of the last tumor assessment prior to the clinical cutoff or at the time of randomization plus 1 day for those without post-baseline assessment.
Time to Deterioration (TTD) in Pain Severity, Based on the Brief Pain Inventory-Short Form (BPI-SF) Questionnaire From Baseline until treatment discontinuation (up to approximately 41 months) TTD in pain severity is defined as time to first documented ≥2-point increase from Baseline in the "Worst Pain" item from the BPI-SF Questionnaire held for at least two consecutive cycles or an initial ≥2-point worsening followed by death or treatment discontinuation within 3 weeks from the last assessment. The BPI-SF is a self administered questionnaire developed to assess the severity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI-SF uses 10-point numeric rating scale, with 0="No pain", "No interference" to 10="Pain as bad as you can imagine", "Highest imaginable interference". A lower score indicates improvement. 95% CI for median was computed using the method of Brookmeyer and Crowley. Strata are: Site of disease, Prior treatment with CDK4/6 inhibitor, and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression.
TTD in Pain Presence and Interference, Based on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Pain Scale Score From Baseline until treatment discontinuation (up to approximately 41 months) TTD in pain presence and interference is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed pain scale score (0-100 scale) held for at least 2 consecutive cycles or an initial ≥10-point worsening followed by death or treatment discontinuation within 3 weeks from the last assessment. EORTC QLQ-C30 is a patient-reported measure with 30 questions assessing 5 aspects of functioning, 3 symptom scales, global health and quality of life, and 6 single items with a recall period of the previous week. The pain scale is scored on a 4-point scale (1=Not at All to 4=Very Much); higher scores indicate worse pain symptoms. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Strata are: Site of disease, Prior treatment with CDK4/6 inhibitor, and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression.
TTD in Role Functioning (RF), Based on the EORTC QLQ-C30 RF Scale Score From Baseline until treatment discontinuation (up to approximately 41 months) TTD in RF is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed RF scale score (0-100 scale) held for at least 2 consecutive cycles or an initial ≥10-point worsening followed by death or treatment discontinuation within 3 weeks from the last assessment. EORTC QLQ-C30 is a patient-reported measure with 30 questions assessing 5 aspects of functioning, 3 symptom scales, global health and quality of life, and 6 single items with a recall period of the previous week. The RF is scored on a 4-point scale (1=Not at All to 4=Very Much); higher scores indicate better function. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Strata are: Site of disease, Prior treatment with CDK4/6 inhibitor, and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression.
TTD in Global Health Status and Quality of Life (GHS/QoL), Based on the EORTC QLQ-C30 GHS/QoL Scale Score From Baseline until treatment discontinuation (up to approximately 41 months) TTD in GHS/QoL is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed RF scale score (0-100 scale) held for at least 2 consecutive cycles or an initial ≥10-point worsening followed by death or treatment discontinuation within 3 weeks from the last assessment. EORTC QLQ-C30 is a patient-reported measure with 30 questions assessing 5 aspects of functioning, 3 symptom scales, global health and quality of life, and 6 single items with a recall period of the previous week. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent); higher scores indicate better QoL. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Strata are: Site of disease, Prior treatment with CDK4/6 inhibitor, and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression.
Number of Participants With Adverse Events (AEs), Severity Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) From first dose until 30 days after final dose of study drug (up to approximately 55 months) An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; any new disease or exacerbation of an existing disease; recurrence of an intermittent medical condition; any deterioration in a laboratory value or other clinical test; AEs that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.
Number of Participants With Vital Sign Abnormalities Over the Course of the Study 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 approximately 55 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 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 approximately 55 months) Hematology parameters include white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin, hematocrit, platelet count, and differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, other cells).
Number of Participants With Clinical Laboratory Test Abnormalities for Biochemistry Parameters Over the Course of the Study 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 approximately 55 months) Biochemistry parameters include bicarbonate or total carbon dioxide, sodium, potassium, chloride, glucose, blood urea nitrogen (BUN) or urea, creatinine, total protein, albumin, phosphate, calcium, total and direct bilirubin, alkaline phosphatase level test (ALP), Alanine transaminase (ALT), aspartate aminotransferase (AST), urate, and lactate dehydrogenase (LDH).
Plasma Concentration of Giredestrant at Specified Timepoints Cycle 1 Day 1 3-hours postdose, Cycle 2 Day 1 predose, Cycle 2 Day 1 3-hour postdose, Cycle 3 Day 1 predose TTD in Physical Functioning (PF), Based on the EORTC QLQ-C30 PF Scale Score From Baseline until treatment discontinuation (up to approximately 41 months) TTD in PF is defined as the time to first documented ≥10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed PF scale score (0-100 scale) held for at least 2 consecutive cycles or an initial ≥10-point worsening followed by death or treatment discontinuation within 3 weeks from the last assessment. EORTC QLQ-C30 is a patient-reported measure with 30 questions assessing 5 aspects of functioning, 3 symptom scales, global health and quality of life, and 6 single items with a recall period of the previous week. The PF scale has 5 questions scored on a 4-point scale (1=Not at All to 4=Very Much); higher scores indicate better function. The 95% CI for median was computed using the method of Brookmeyer and Crowley. Strata are: Site of disease, Prior treatment with CDK4/6 inhibitor, and Prior treatment with fulvestrant. Hazard ratios were estimated by Cox regression.
Trial Locations
- Locations (84)
Northwest Georgia Oncology Centers PC - Marietta
🇺🇸Marietta, Georgia, United States
University Hospitals Seidman Cancer Center
🇺🇸Cleveland, Ohio, United States
Northwest Cancer Specialists - Portland (SW Barnes Rd)
🇺🇸Tigard, Oregon, United States
Fundación CENIT para la Investigación en Neurociencias
🇦🇷Buenos Aires, Argentina
Instituto Angel Roffo
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Fundación Scherbovsky
🇦🇷Mendoza, Argentina
Hosp Provincial D. Centenarios
🇦🇷Rosario, Argentina
Organizacion Medica de Investigacion
🇦🇷San Nicolás, Argentina
Kinghorn Cancer Centre
🇦🇺Darlinghurst, New South Wales, Australia
Sunshine Hospital
🇦🇺St Albans, Victoria, Australia
Scroll for more (74 remaining)Northwest Georgia Oncology Centers PC - Marietta🇺🇸Marietta, Georgia, United States