A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Fulvestrant Versus Placebo + Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Breast Cancer Following Recurrence or Progression On or After Treatment With an Aromatase Inhibitor
Overview
- Phase
- Phase 3
- Intervention
- Fulvestrant
- Conditions
- Locally Advanced (Inoperable) or Metastatic Breast Cancer
- Sponsor
- AstraZeneca
- Enrollment
- 818
- Locations
- 216
- Primary Endpoint
- Progression Free Survival: Overall Population (Months) in the Global Cohort
- Status
- Active, not recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
Phase III, double-blind, randomised study assessing the efficacy of capivasertib + fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer following recurrence or progression on or after AI therapy.
Detailed Description
Phase III, double-blind, randomised study assessing the efficacy of capivasertib + fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) breast cancer following recurrence or progression on or after aromatase inhibitor (AI) therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue on it for the duration of the study
- •Histologically confirmed HR+/HER2- breast cancer determined from the most recent tumour sample (primary or metastatic), as per the American Society of Clinical Oncology and College of American Pathologists guideline recommendations. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor.
- •Metastatic or locally advanced disease with radiological or objective evidence of recurrence or progression (the cancer should have shown progression during or after most recent therapy); locally advanced disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)
- •ECOG/WHO PS: 0-1
- •Patients are to have received treatment with an AI (aromatase inhibitor) containing regimen (single agent or in combination) and have:
- •Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an AI, OR
- •Radiological evidence of progression while on prior AI administered as a treatment line for locally advanced or metastatic breast cancer (this does not need to be the most recent therapy)
- •Patients must have measurable disease according to RECIST 1.1 and/or at least 1 lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible
- •FFPE tumour sample from primary/recurrent cancer for central testing
Exclusion Criteria
- •Symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgement
- •More than 2 lines of endocrine therapy for inoperable locally advanced or metastatic disease
- •More than 1 line of chemotherapy for inoperable locally advanced or metastatic disease. Adjuvant and neoadjuvant chemotherapy are not classed as lines of chemotherapy for advanced breast cancer
- •Prior treatment with any of the following:
- •AKT, PI3K and mTOR inhibitors
- •Fulvestrant, and other SERDs
- •Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks prior to study treatment initiation.
- •Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort) or drugs that are sensitive to CYP3A4 inhibition within 1 week prior to study treatment initiation.
- •Radiotherapy with a wide field of radiation up to 4 weeks before study treatment initiation (capivasertib/placebo) and/or radiotherapy with a limited field of radiation for palliation up to 2 weeks before study treatment initiation (capivasertib/placebo)
- •With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment
Arms & Interventions
Capivasertib + fulvestrant
Fulvestrant: 2 intramuscular injections of 500 mg given on Day 1 of Weeks 1 and 3 of cycle 1, and then on Day 1, Week 1 of each cycle thereafter. Capivasertib: 400 mg (2 oral tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 1 to 4 in each week of a 28-day treatment cycle.
Intervention: Fulvestrant
Capivasertib + fulvestrant
Fulvestrant: 2 intramuscular injections of 500 mg given on Day 1 of Weeks 1 and 3 of cycle 1, and then on Day 1, Week 1 of each cycle thereafter. Capivasertib: 400 mg (2 oral tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 1 to 4 in each week of a 28-day treatment cycle.
Intervention: Capivasertib
Placebo + fulvestrant
Fulvestrant: 2 intramuscular injections of 500 mg given on Day 1 of Weeks 1 and 3 of cycle 1, and then on Day 1, Week 1 of each cycle thereafter. Placebo: 400 mg (2 oral tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 1 to 4 in each week of a 28-day treatment cycle.
Intervention: Fulvestrant
Placebo + fulvestrant
Fulvestrant: 2 intramuscular injections of 500 mg given on Day 1 of Weeks 1 and 3 of cycle 1, and then on Day 1, Week 1 of each cycle thereafter. Placebo: 400 mg (2 oral tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 1 to 4 in each week of a 28-day treatment cycle.
Intervention: Placebo
Outcomes
Primary Outcomes
Progression Free Survival: Overall Population (Months) in the Global Cohort
Time Frame: Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Participants who discontinue treatment prior to progression should continue to be scanned until progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s).
Progression Free Survival: Overall Population (Percentage) in the Global Cohort
Time Frame: Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used.
Progression Free Survival: Altered Population (Months) in the Global Cohort
Time Frame: Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause.
Progression Free Survival: Altered Population (Percentage) in the Global Cohort
Time Frame: Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Kaplan-Meier estimate was used.
Progression Free Survival: Overall Population (Months) in the China Cohort
Time Frame: Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression.
Progression Free Survival: Overall Population (Percentage) in the China Cohort
Time Frame: Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used.
Progression Free Survival: Altered Population (Months) in the China Cohort
Time Frame: Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause.
Progression Free Survival: Altered Population (Percentage) in the China Cohort
Time Frame: Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause Kaplan-Meier estimate was used.