NCT04305496 · CITED IN SOURCE DOCUMENTS

Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/HER2- Breast Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-04-30

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression Free Survival: Overall Population (Months) in the Global Cohort

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outcome · POSTED

Progression Free Survival: Overall Population (Percentage) in the Global Cohort

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outcome · POSTED

Progression Free Survival: Altered Population (Months) in the Global Cohort

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outcome · POSTED

Progression Free Survival: Altered Population (Percentage) in the Global Cohort

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outcome · POSTED

Progression Free Survival: Overall Population (Months) in the China Cohort

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outcome · POSTED

Progression Free Survival: Overall Population (Percentage) in the China Cohort

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outcome · POSTED

Progression Free Survival: Altered Population (Months) in the China Cohort

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outcome · POSTED

Progression Free Survival: Altered Population (Percentage) in the China Cohort

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: 1. 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 2. 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. 3. 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) 4. ECOG/WHO PS: 0-1 5. Patients are to have received treatment with an AI (aromatase inhibitor) containing regimen (single agent or in combination) and have: 1. 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 2. 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) 6. 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 7. FFPE tumour sample from primary/recurrent cancer for central testing Exclusion Criteria: 1. Symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgement 2. More than 2 lines of endocrine therapy for inoperable locally advanced or metastatic disease 3. 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 4. Prior treatment with any of the following: 1. AKT, PI3K and mTOR inhibitors 2. Fulvestrant, and other SERDs 3. Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks prior to study treatment initiation. 4. 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. 5. 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) 6. With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment 7. Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids up to 4 weeks before study treatment initiation 8. Any of the following cardiac criteria: 1. Mean resting QT interval corrected by Fridericia's formula (QTcF) \>470 msec obtained from 3 consecutive ECGs 2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block) 3. Any factors that increase the risk of corrected QT interval (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval 4. Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥2 5. Uncontrolled hypotension - systolic blood pressure \<90 mmHg and/or diastolic blood pressure \<50 mmHg 6. Cardiac ejection fraction outside institutional range of normal or \<50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition \[MUGA\] scan if an echocardiogram cannot be performed or is inconclusive) 9. Clinically significant abnormalities of glucose metabolism as defined by any of the following: 1. Patients with diabetes mellitus type 1 or diabetes mellitus type 2 requiring insulin treatment 2. HbA1c ≥8.0% (63.9 mmol/mol) 10. Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or LHRH agonist (if applicable) 11. Currently pregnant (confirmed with positive pregnancy test) or breast-feeding
healthy Volunteers: false
maximum Age: 130 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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 Names
Drug: Fulvestrant
Drug: Capivasertib
label
Capivasertib + fulvestrant
type
EXPERIMENTAL
description
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 Names
Drug: Fulvestrant
Drug: Placebo
label
Placebo + fulvestrant
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Capivasertib + fulvestrant
Placebo + fulvestrant
description
Patients will be administered 500 mg (2 injections) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter
name
Fulvestrant
type
DRUG
arm Group Labels
Capivasertib + fulvestrant
description
400 mg BD (2 tablets of 200 mg taken twice a day = total daily dose 800 mg) given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle
name
Capivasertib
type
DRUG
arm Group Labels
Placebo + fulvestrant
description
Placebo to match 400 mg BD (2 tablets of placebo to match 200 mg taken twice daily = placebo to match total daily dose of 800 mg) given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

intervention Model Description

Double-blind Randomised Study

masking Info

masking: QUADRUPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 818
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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).
measure
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.
description
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.
measure
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.
description
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.
measure
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.
description
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.
measure
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.
description
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.
measure
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.
description
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.
measure
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.
description
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.
measure
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.
description
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.
measure
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.

Full study description

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.

Source references

references

citation
Turner NC, Oliveira M, Howell SJ, Dalenc F, Cortes J, Gomez Moreno HL, Hu X, Jhaveri K, Krivorotko P, Loibl S, Morales Murillo S, Okera M, Park YH, Sohn J, Toi M, Tokunaga E, Yousef S, Zhukova L, de Bruin EC, Grinsted L, Schiavon G, Foxley A, Rugo HS; CAPItello-291 Study Group. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2023 Jun 1;388(22):2058-2070. doi: 10.1056/NEJMoa2214131.
pmid
37256976
type
BACKGROUND
citation
Turner NC, Oliveira M, Howell SJ, Dalenc F, Cortes J, Gomez HL, Hu X, Jhaveri K, Krivorotko P, Loibl S, Murillo SM, Park YH, Sohn JH, Toi M, Tokunaga E, Yousef S, Zhukova L, de Bruin E, Grinsted L, Schiavon G, Foxley A, Rugo HS. A plain language summary of the CAPItello-291 study: Capivasertib in hormone receptor-positive advanced breast cancer. Future Oncol. 2024;20(37):2901-2913. doi: 10.1080/14796694.2024.2390791. Epub 2024 Sep 16.
pmid
39283299
type
DERIVED
citation
Oliveira M, Rugo HS, Howell SJ, Dalenc F, Cortes J, Gomez HL, Hu X, Toi M, Jhaveri K, Krivorotko P, Loibl S, Morales Murillo S, Okera M, Nowecki Z, Park YH, Sohn JH, Tokunaga E, Yousef S, Zhukova L, Fulford M, Andrews H, Wadsworth I, D'Cruz C, Turner NC; CAPItello-291 study group. Capivasertib and fulvestrant for patients with hormone receptor-positive, HER2-negative advanced breast cancer (CAPItello-291): patient-reported outcomes from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2024 Sep;25(9):1231-1244. doi: 10.1016/S1470-2045(24)00373-5.
pmid
39214106
type
DERIVED
citation
Dilawari A, Buturla J, Osgood C, Gao X, Chen W, Ricks TK, Schaefer T, Avasarala S, Reyes Turcu F, Pathak A, Kalavar S, Bhatnagar V, Collazo J, Rahman NA, Mixter B, Tang S, Pazdur R, Kluetz P, Amiri-Kordestani L. US Food and Drug Administration Approval Summary: Capivasertib With Fulvestrant for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer With PIK3CA/AKT1/PTEN Alterations. J Clin Oncol. 2024 Dec;42(34):4103-4113. doi: 10.1200/JCO.24.00427. Epub 2024 Aug 19.
pmid
39159418
type
DERIVED