Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)
CAPItello-292
A Phase Ib/III, Open-label, Randomised Study of Capivasertib Plus CDK4/6 Inhibitors and Fulvestrant Versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292)
2 other identifiers
interventional
893
23 countries
225
Brief Summary
A Phase Ib/III Open-label, Randomised Study of Capivasertib plus CDK4/6 Inhibitors and Fulvestrant versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started May 2021
Longer than P75 for phase_3
225 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 17, 2021
CompletedFirst Posted
Study publicly available on registry
April 28, 2021
CompletedStudy Start
First participant enrolled
May 10, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 14, 2029
August 17, 2026
August 1, 2026
6.5 years
March 17, 2021
August 14, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Phase Ib: 1. The number of participants with dose-limiting toxicity, as defined in the protocol.
Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria.
Within the first 28 day cycle.
Phase Ib: 2. The number of participants with treatment-related adverse events.
Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.
From baseline up to approximately 36 months.
Phase Ib: 3. The number of participants with treatment-related serious adverse events.
Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.
From baseline up to approximately 36 months.
Phase III: 1. Progression Free Survival (PFS).
Progression Free Survival (PFS) is defined as time from randomization until progression per RECIST v1.1. as assessed by BICR or death due to any cause in the overall population, the altered population, and the confirmed non-altered population. RECIST related endpoints such as PFS, ORR, DoR, CBR will be collected.
Up to approximately 47 months.
Secondary Outcomes (22)
Phase Ib: 1. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmax.
Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days).
Phase Ib: 2. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-72h.
Cycle 0 (Cycle 0 is 3 days).
Phase Ib: 3. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-24h.
Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days).
Phase Ib: 4. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmin.
Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 0 is 3 days and Cycle 1 is 28 days).
Phase Ib: 5. PK parameters for capivasertib: Cmax.
Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).
- +17 more secondary outcomes
Study Arms (5)
Capivasertib Plus Palbociclib and Fulvestrant
EXPERIMENTALCapivasertib Plus Palbociclib and Fulvestrant (Ph 1b)
Capivasertib Plus Ribociclib and Fulvestrant
EXPERIMENTALCapivasertib Plus Ribociclib and Fulvestrant (Ph 1b)
Capivasertib Plus Abemaciclib and Fulvestrant
EXPERIMENTALCapivasertib Plus Abemaciclib and Fulvestrant (Ph 1b)
Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib)
EXPERIMENTALCapivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III)
Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib)
ACTIVE COMPARATORFulvestrant and investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III)
Interventions
Phase Ib: 50 mg/ 100 mg/ 150 mg. Twice daily for 28 consecutive days to comprise a complete 28-day cycle
Phase Ib: Capivasertib 320 mg/ 400 mg administered PO BD 4 days on /3 days off per week for 4 weeks (28 days cycle) Phase III: : Capivasertib, administered PO BD 4 days on / 3 days off per week for 4 weeks (28 days cycle) at the dose confirmed in the phase Ib portion
Phase Ib and Phase III: 500 mg (2 injections of 250 mg) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter
Phase Ib: 100 mg/ 125 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose of 125 mg.
Phase Ib: 200 mg/ 400 mg/ 600 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose confirmed in the phase 1b portion.
Eligibility Criteria
You may qualify if:
- Adult females (pre-/peri-/ and post-menopausal), and adult males.
- Histologically confirmed HR+/ HER2- breast cancer determined from the most recent tumour sample (primary or metastatic) per the American Society of Clinical Oncology and College of American Pathologists guideline. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor.
- Eligible for fulvestrant therapy and at least one of the following: palbociclib, ribociclib, or abemaciclib, as per local investigator assessment. Previous tolerance to specific CDK4/6 inhibitors and dose levels required.
- Adequate organ and bone marrow functions.
- Consent to provide a mandatory FFPE tumour sample.
- Previous treatment with an ET (tamoxifen, AI, or oral SERD) as a single agent or in combination, with radiological evidence of breast cancer recurrence or progression while on, or within 12 months of, completing a (neo)adjuvant ET regimen.
- Provision of mandatory blood samples at screening for central testing using an investigational ctDNA test to be stratified based on PIK3CA/AKT1/PTEN status.
- Be eligible for fulvestrant and at least one out of palbociclib or ribociclib (depending on the available CDK4/6i options at time of enrolment), as per local investigator assessment.
- Have measurable lesion(s) according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) or, in the absence of measurable disease, lytic or mixed bone lesions that can be assessed by computed tomography (CT) or magnetic resonance imaging (MRI).
You may not qualify if:
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence.
- Radiotherapy within 2 weeks prior to study treatment initiation.
- Major surgery or significant traumatic injury within 4 weeks of the first dose of study treatment.
- Persistent toxicities (CTCAE Grade \>1) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss or peripheral sensory neuropathy) after consultation with the AstraZeneca study physician.
- Spinal cord compression, brain metastases or leptomeningeal metastases unless these lesions are definitively treated (eg. radiotherapy, surgery) and clinically stable off steroids for management of symptoms for at least 4 weeks prior to study treatment initiation.
- Any of the following cardiac criteria at screening:
- (a). Mean resting corrected QT interval (QTcF): (i) Participants to be treated with palbociclib:: QTcF ≥ 470 ms obtained from the average of 3 consecutive (triplicate) ECGs (ii) Participants to be treated with ribociclib: QTcF ≥ 450 ms obtained from the average of 3 consecutive (triplicate) ECGs (iii) Participants to be treated with abemaciclib (Phase Ib only): QTcF ≥ 470 ms obtained from the average of 3 consecutive (triplicate) ECGs (b). Any clinically important abnormalities in cardiac rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third-degree heart block) (c). Any factors that increase the risk of QTc prolongation or risk of arrhythmic events (d). Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥ 2 (e). Uncontrolled hypotension (f) uncontrolled hypertension (g). Cardiac ejection fraction outside institutional range of normal or \< 50% (whichever is higher)
- uncontrolled or high grade or symptomatic arrhythmia and atrial fibrillation
- Any of these clinically significant abnormalities of glucose metabolism at screening:
- diabetes mellitus type I or type II requiring insulin treatment
- Glycated haemoglobin (HbA1c) ≥ 8.0% (63.9 mmol/mol)
- Previous allogeneic bone marrow transplant or solid organ transplant.
- Any prior treatment with, AKT, PI3K or mTOR inhibitors.
- Prior treatment with CDK4/6 inhibitors in the metastatic setting (prior CDK4/6 inhibitors permitted in the adjuvant setting provided there was a CDK4/6i treatment free interval of at least 12 months).
- More than 1 line of chemotherapy for metastatic disease.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (225)
Research Site
Tucson, Arizona, 85719, United States
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Fountain Valley, California, 92708, United States
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Glendale, California, 91204, United States
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Los Angeles, California, 90033, United States
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Napa, California, 94558, United States
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San Francisco, California, 94158, United States
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Santa Rosa, California, 92805, United States
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Aurora, Colorado, 80045, United States
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New Haven, Connecticut, 06510, United States
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Newark, Delaware, 19713, United States
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Louisville, Kentucky, 40202, United States
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Annapolis, Maryland, 21401, United States
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Boston, Massachusetts, 02215, United States
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Detroit, Michigan, 48236, United States
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Grand Rapids, Michigan, 49503, United States
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Hannibal, Missouri, 63401, United States
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St Louis, Missouri, 63110, United States
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Omaha, Nebraska, 68130, United States
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Camden, New Jersey, 08103, United States
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Mineola, New York, 11501, United States
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New York, New York, 10016, United States
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New York, New York, 10065, United States
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Gresham, Oregon, 97030, United States
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Philadelphia, Pennsylvania, 19104, United States
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Pittsburgh, Pennsylvania, 15213, United States
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York, Pennsylvania, 17403, United States
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Greenville, South Carolina, 29607, United States
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Chattanooga, Tennessee, 37404, United States
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Nashville, Tennessee, 37203, United States
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Dallas, Texas, 75246, United States
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Houston, Texas, 77030, United States
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Irving, Texas, 75063, United States
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San Antonio, Texas, 78229, United States
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San Antonio, Texas, 78240, United States
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Salt Lake City, Utah, 84106, United States
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Fairfax, Virginia, 22031, United States
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Falls Church, Virginia, 22042, United States
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Midlothian, Virginia, 23114, United States
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Norfolk, Virginia, 23502, United States
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Tacoma, Washington, 98405, United States
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Buenos Aires, 1439, Argentina
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CABA, 1414, Argentina
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CABA, 1425, Argentina
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CABA, C1113AAE, Argentina
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CABA, C1425, Argentina
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Chivilcoy, B6620LUD, Argentina
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Rosario, 2000, Argentina
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Darlinghurst, 2010, Australia
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Nedlands, 6009, Australia
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Waratah, 2298, Australia
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Brasschaat, 2930, Belgium
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Brussels, 1200, Belgium
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Edegem, 2650, Belgium
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Haine-Saint-Paul, 7100, Belgium
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Leuven, 3000, Belgium
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Alfenas, 37130-000, Brazil
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Blumenau, 89010-340, Brazil
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Natal, 59075-740, Brazil
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Porto Alegre, 90035-903, Brazil
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Porto Velho, 76834-899, Brazil
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São Paulo, 04014-002, Brazil
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Taubaté, 12030-200, Brazil
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Teresina, 64049-200, Brazil
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Vitória, 29043-260, Brazil
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Abbotsford British Columbia, British Columbia, V2S0C2, Canada
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Kelowna, British Columbia, V1Y 5L3, Canada
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Halifax, Nova Scotia, B3H 1V7, Canada
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Brampton, Ontario, L6R 3J7, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Toronto, Ontario, M5B 1W8, Canada
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Sherbrooke, Quebec, J1H 5N4, Canada
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Chicoutimi, G7H 5H6, Canada
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Montreal, H3T 1E2, Canada
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Beijing, 100039, China
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Beijing, 100044, China
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Beijing, 100191, China
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Beijing, 100210, China
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Bengbu, 233004, China
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Changchun, 130000, China
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Changsha, 410013, China
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Chengdu, 610041, China
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Chongqing, 400042, China
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Guangzhou, 510060, China
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Guangzhou, 510062, China
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Hangzhou, 31000, China
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Hangzhou, 310022, China
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Hefei, 230031, China
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Nanchang, 330006, China
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Nanchang, 330009, China
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Nanjing, 210029, China
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Nanning, 530021, China
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Shandong, China
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Shanghai, 200032, China
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Shenyang, 110001, China
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Shenyang, 110016, China
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Ürümqi, 830000, China
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Wuhan, 430060, China
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Xi'an, 710061, China
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Xuzhou, 221009, China
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Zhengzhou, 450008, China
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Aalborg, 9000, Denmark
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Aarhus N, 8200, Denmark
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Hillerød, 3400, Denmark
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Odense, 5000, Denmark
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Bobigny, 93000, France
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Limoges, 87042, France
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Lyon, 69008, France
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Plérin, 22190, France
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Rouen, 76021, France
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Saint-Herblain, 44805, France
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Villejuif, 94805, France
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Augsburg, 86150, Germany
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Dresden, 01307, Germany
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Erlangen, 91054, Germany
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Essen, 45136, Germany
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Frankfurt am Main, 65929, Germany
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Freiburg im Breisgau, 79106, Germany
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Georgsmarienhütte, 49124, Germany
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Hanover, 30625, Germany
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Heilbronn, 74078, Germany
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Kiel, 24105, Germany
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Leipzig, 04103, Germany
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Mannheim, 68167, Germany
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Mönchengladbach, 41061, Germany
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Regensburg, 93053, Germany
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Ulm, 89075, Germany
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Bangalore, 560004, India
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Mohali, 160055, India
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Mysuru, 570017, India
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Nagpur, 440001, India
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New Delhi, 110075, India
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New Delhi, 110076, India
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Vadodara, 391760, India
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Varanasi, 221005, India
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Bologna, 40138, Italy
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Florence, 50141, Italy
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Misterbianco, 95045, Italy
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Naples, 80131, Italy
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Padova, 35128, Italy
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Prato, 59100, Italy
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Roma, 00168, Italy
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Chiba, 260-8717, Japan
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Chūōku, 104-0045, Japan
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Chūōku, 104-8560, Japan
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Hidaka-shi, 350-1298, Japan
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Hiroshima, 730-8518, Japan
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Isehara-shi, 259-1193, Japan
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Kagoshima, 892-0833, Japan
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Kōtoku, 135-8550, Japan
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Kyoto, 606-8507, Japan
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Matsuyama, 791-0280, Japan
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Naha, 901-0154, Japan
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Osaka, 541-8567, Japan
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Ota-shi, 373-8550, Japan
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Sapporo, 060-8638, Japan
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Sendai, 980-8574, Japan
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Shimotsuke-shi, 329-0498, Japan
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Shinagawa-ku, 142-8666, Japan
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Shinjuku-ku, 162-8655, Japan
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Suita-shi, 565-0871, Japan
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Takasaki-shi, 370-0829, Japan
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Tsu, 514-8507, Japan
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Yokohama, 241-8515, Japan
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George Town, 10350, Malaysia
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Kuala Lumpur, 50586, Malaysia
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Kuala Lumpur, 59100, Malaysia
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Kuala Selangor, 46050, Malaysia
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Kuala Selangor, 62250, Malaysia
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Kuching, 93586, Malaysia
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Pulau Pinang, 10450, Malaysia
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Bydgoszcz, 85-796, Poland
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Krakow, 31-501, Poland
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Warsaw, 02-781, Poland
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Goyang-si, 10408, South Korea
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Seoul, 02841, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 06273, South Korea
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Seoul, 06351, South Korea
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Seoul, 5505, South Korea
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Barcelona, 8035, Spain
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Granada, 18014, Spain
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Lleida, 25198, Spain
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Madrid, 28034, Spain
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Madrid, 28040, Spain
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Málaga, 29010, Spain
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Pamplona, 31008, Spain
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Santiago de Compostela, 15706, Spain
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Lund, 221 85, Sweden
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Solna, 17176, Sweden
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Kaohsiung City, 80756, Taiwan
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Kaohsiung City, 83301, Taiwan
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Taichung, 40705, Taiwan
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Taichung, Taiwan
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Tainan, 704, Taiwan
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Taipei, 10002, Taiwan
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Taipei, 10449, Taiwan
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Taoyuan, 333, Taiwan
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Bangkok, 10210, Thailand
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Bangkok, 10330, Thailand
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Bangkok, 10400, Thailand
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Bangkok, 10700, Thailand
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Chiang Mai, 50200, Thailand
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Dusit, 10300, Thailand
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Hat Yai, 90110, Thailand
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Khon Kaen, 40002, Thailand
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Lampang, 52000, Thailand
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Ratchathewi, 10400, Thailand
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Ankara, 6100, Turkey (Türkiye)
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Antalya, 07070, Turkey (Türkiye)
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Cordaleo, 35575, Turkey (Türkiye)
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Goztepe Istanbul, Turkey (Türkiye)
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Malatya, 44280, Turkey (Türkiye)
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Samsun, 55200, Turkey (Türkiye)
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Guildford, CU2 7XX, United Kingdom
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London, SE1 9RT, United Kingdom
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Londonderry, BT47 6SB, United Kingdom
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Taunton, TA1 5DA, United Kingdom
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York, YO21 8HE, United Kingdom
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Can Tho, 900000, Vietnam
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Hanoi, 100000, Vietnam
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Ho Chi Minh City, 700000, Vietnam
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Ho Chi Minh City, 70000, Vietnam
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Hồ Chí Minh, 700000, Vietnam
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Vinh, 460000, Vietnam
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 17, 2021
First Posted
April 28, 2021
Study Start
May 10, 2021
Primary Completion (Estimated)
November 1, 2027
Study Completion (Estimated)
August 14, 2029
Last Updated
August 17, 2026
Record last verified: 2026-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.