Brief Summary
This Phase 3 clinical study compares the efficacy and safety of elacestrant to the standard of care (SoC) options of fulvestrant or an aromatase inhibitor (AI) in women and men with breast cancer whose disease has advanced on at least one endocrine therapy including a CDK4/6 inhibitor in combination with fulvestrant or an aromatase inhibitor (AI) .
Brief Title
Phase 3 Trial of Elacestrant vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer
Detailed Description
This is an international, multicenter, randomized, open-label, active-controlled, event-driven, Phase 3 clinical study comparing the efficacy and safety of elacestrant to the SoC options of fulvestrant or an aromatase inhibitor (AI) in postmenopausal women and in men with advanced or metastatic ER+/HER2- breast cancer, either in subjects with tumors that harbor mutations in the ligand binding domain (LBD) of the estrogen receptor 1 (ESR1) gene (ESR1-mut subjects) or in all subjects regardless of ESR1 status (ESR1-mut and ESR1 wild type \[ESR1-WT\]) and whose disease has relapsed or progressed on at least one and no more than two prior lines of endocrine therapy (with documented progression), which must have included prior CDK4/6 inhibitor therapy in combination with fulvestrant or an aromatase inhibitor (AI) and for whom hormonal monotherapy with one of the SoC drugs (fulvestrant, anastrozole, letrozole, exemestane) is an appropriate treatment option.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Breast Cancer
Eligibility Criteria
Critical Inclusion Criteria:
1. Subjects with proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy.
2. Subjects must be appropriate candidates for endocrine monotherapy
3. Subjects must have measurable disease or bone only disease
4. Female or male subjects age ≥ 18 years; female subjects must be postmenopausal women and male subjects must not allow pregnancy with their sperm (abstain, do not donate sperm, etc).
5. Subjects must have ER+ and HER2- tumor status
6. Subjects must have previously received at least one and no more than two lines of endocrine therapy for advanced/metastatic breast cancer and meet additional previous treatment criteria.
7. Subjects must have received prior treatment with a CDK4/6 inhibitor in combination with either fulvestrant or an aromatase inhibitor (AI) for advanced/metastatic breast cancer (mBC).
8. Subjects may have received no more than one line of chemotherapy in the advanced/metastatic setting.
Critical Exclusion Criteria:
1. Prior treatment with elacestrant or other investigational selective estrogen receptor degrader (SERD) or ER antagonist (D-0502, GDC-0810, GDC- 0927, GDC-9545, G1T-48, LSZ102, AZD9496, SAR439859, ZN-c5, H3B-6545, bazedoxifene, lasofoxifene).
2. Prior anticancer or investigational drug treatment within the following windows:
1. Fulvestrant treatment \< 42 days before first dose of study drug
2. Any endocrine therapy \< 14 days before first dose of study drug
3. Chemotherapy \< 21 days before first dose of study drug
4. Any investigational anti-cancer drug therapy \< 28 days or five half-lives (whichever is shorter) before the first dose of study drug. Enrollment of subjects whose most recent therapy was an investigational agent should be discussed with the Sponsor
5. Bisphosphonates or RANKL inhibitors initiated or dose changed \< 3 months prior to first dose of study drug
3. Presence of symptomatic visceral disease as defined in protocol.
1. Subjects with proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy.
2. Subjects must be appropriate candidates for endocrine monotherapy
3. Subjects must have measurable disease or bone only disease
4. Female or male subjects age ≥ 18 years; female subjects must be postmenopausal women and male subjects must not allow pregnancy with their sperm (abstain, do not donate sperm, etc).
5. Subjects must have ER+ and HER2- tumor status
6. Subjects must have previously received at least one and no more than two lines of endocrine therapy for advanced/metastatic breast cancer and meet additional previous treatment criteria.
7. Subjects must have received prior treatment with a CDK4/6 inhibitor in combination with either fulvestrant or an aromatase inhibitor (AI) for advanced/metastatic breast cancer (mBC).
8. Subjects may have received no more than one line of chemotherapy in the advanced/metastatic setting.
Critical Exclusion Criteria:
1. Prior treatment with elacestrant or other investigational selective estrogen receptor degrader (SERD) or ER antagonist (D-0502, GDC-0810, GDC- 0927, GDC-9545, G1T-48, LSZ102, AZD9496, SAR439859, ZN-c5, H3B-6545, bazedoxifene, lasofoxifene).
2. Prior anticancer or investigational drug treatment within the following windows:
1. Fulvestrant treatment \< 42 days before first dose of study drug
2. Any endocrine therapy \< 14 days before first dose of study drug
3. Chemotherapy \< 21 days before first dose of study drug
4. Any investigational anti-cancer drug therapy \< 28 days or five half-lives (whichever is shorter) before the first dose of study drug. Enrollment of subjects whose most recent therapy was an investigational agent should be discussed with the Sponsor
5. Bisphosphonates or RANKL inhibitors initiated or dose changed \< 3 months prior to first dose of study drug
3. Presence of symptomatic visceral disease as defined in protocol.
Inclusion Criteria
Inclusion Criteria:
1. Subjects with proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy.
2. Subjects must be appropriate candidates for endocrine monotherapy
3. Subjects must have measurable disease or bone only disease
4. Female or male subjects age ≥ 18 years; female subjects must be postmenopausal women and male subjects must not allow pregnancy with their sperm (abstain, do not donate sperm, etc).
5. Subjects must have ER+ and HER2- tumor status
6. Subjects must have previously received at least one and no more than two lines of endocrine therapy for advanced/metastatic breast cancer and meet additional previous treatment criteria.
7. Subjects must have received prior treatment with a CDK4/6 inhibitor in combination with either fulvestrant or an aromatase inhibitor (AI) for advanced/metastatic breast cancer (mBC).
8. Subjects may have received no more than one line of chemotherapy in the advanced/metastatic setting.
Critical
1. Subjects with proven diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy.
2. Subjects must be appropriate candidates for endocrine monotherapy
3. Subjects must have measurable disease or bone only disease
4. Female or male subjects age ≥ 18 years; female subjects must be postmenopausal women and male subjects must not allow pregnancy with their sperm (abstain, do not donate sperm, etc).
5. Subjects must have ER+ and HER2- tumor status
6. Subjects must have previously received at least one and no more than two lines of endocrine therapy for advanced/metastatic breast cancer and meet additional previous treatment criteria.
7. Subjects must have received prior treatment with a CDK4/6 inhibitor in combination with either fulvestrant or an aromatase inhibitor (AI) for advanced/metastatic breast cancer (mBC).
8. Subjects may have received no more than one line of chemotherapy in the advanced/metastatic setting.
Critical
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03778931
Org Class
Industry
Org Full Name
Stemline Therapeutics, Inc.
Org Study Id
RAD1901-308
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Elacestrant Monotherapy vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer Following CDK4/6 Inhibitor Therapy: A Phase 3 Randomized, Open-label, Active-controlled, Multicenter Trial
Primary Outcomes
Outcome Description
Progression-free Survival based on blinded IRC assessment in ESR1-mut subjects defined as the length of time from randomization until the date of objective disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as assessed by the blinded IRC or death from any cause. Progression is defined per RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome Measure
Progression-free Survival in ESR1-mut Subjects
Outcome Time Frame
From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months)
Outcome Description
Progression-free Survival based on blinded Imaging Review Committee (IRC) assessment in all (ESR1-mut and ESR1-WT) subjects
Outcome Measure
Progression-free Survival in All Subjects
Outcome Time Frame
From Date of Randomization until Disease Progression or Death Due to Any Cause (up to 12 Months)
Secondary Outcomes
Outcome Description
Overall Survival in ESR1-mut subjects, where Overall Survival is defined as the length of time from randomization until the date of death from any cause
Outcome Time Frame
From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months)
Outcome Measure
Overall Survival in ESR1-mut Subjects
Outcome Description
Overall Survival in All (ESR1-mut and ESR1-WT) Subjects
Outcome Time Frame
From Date of Randomization until Death Due to Any Cause (Estimated up to 24 Months)
Outcome Measure
Overall Survival in All Subjects
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Della Makower
Investigator Email
DMAKOWER@montefiore.org
Investigator Phone