Locally Advanced (Inoperable) or Metastatic Breast CancerPhase 3CAPItello-292NCT04862663
Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)
A Phase 3 study testing Capivasertib, Fulvestrant and Palbociclib in people with Locally Advanced (Inoperable) or Metastatic Breast Cancer, run by AstraZeneca at 225 sites in 23 countries.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Locally Advanced (Inoperable) or Metastatic Breast Cancer
- What is being tested?
- Capivasertib, Fulvestrant and Palbociclib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 893 participants
- Where
- 225 sitesin 23 countries
- Study dates
- 10 May 2021to 14 Aug 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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:
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- (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.
- Any line of endocrine-based therapy for inoperable locally advanced or metastatic disease.
Trial locations and contacts
225 sites in 23 countries.
225 sites in 23 countries
United States40 sites
Research Site
Annapolis, Maryland, 21401
Research Site
Aurora, Colorado, 80045
Research Site
Boston, Massachusetts, 02215
Research Site
Camden, New Jersey, 08103
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Chattanooga, Tennessee, 37404
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Dallas, Texas, 75246
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Detroit, Michigan, 48236
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Fairfax, Virginia, 22031
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Falls Church, Virginia, 22042
Research Site
Fountain Valley, California, 92708
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Glendale, California, 91204
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Grand Rapids, Michigan, 49503
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Greenville, South Carolina, 29607
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Gresham, Oregon, 97030
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Hannibal, Missouri, 63401
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Houston, Texas, 77030
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Irving, Texas, 75063
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Los Angeles, California, 90033
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Louisville, Kentucky, 40202
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Midlothian, Virginia, 23114
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Mineola, New York, 11501
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Napa, California, 94558
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Nashville, Tennessee, 37203
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New Haven, Connecticut, 06510
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New York, New York, 10016
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New York, New York, 10065
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Newark, Delaware, 19713
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Norfolk, Virginia, 23502
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Omaha, Nebraska, 68130
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Philadelphia, Pennsylvania, 19104
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Pittsburgh, Pennsylvania, 15213
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Salt Lake City, Utah, 84106
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San Antonio, Texas, 78229
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San Antonio, Texas, 78240
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San Francisco, California, 94158
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Santa Rosa, California, 92805
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St Louis, Missouri, 63110
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Tacoma, Washington, 98405
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Tucson, Arizona, 85719
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York, Pennsylvania, 17403
China27 sites
Research Site
Beijing, 100039
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Beijing, 100044
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Beijing, 100191
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Beijing, 100210
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Bengbu, 233004
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Changchun, 130000
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Changsha, 410013
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Chengdu, 610041
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Chongqing, 400042
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Guangzhou, 510060
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Guangzhou, 510062
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Hangzhou, 31000
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Hangzhou, 310022
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Hefei, 230031
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Nanchang, 330006
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Nanchang, 330009
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Nanjing, 210029
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Nanning, 530021
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Shandong
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Shanghai, 200032
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Shenyang, 110001
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Shenyang, 110016
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Ürümqi, 830000
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Wuhan, 430060
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Xi'an, 710061
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Xuzhou, 221009
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Zhengzhou, 450008
Japan22 sites
Research Site
Chiba, 260-8717
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Chūōku, 104-0045
Research Site
Chūōku, 104-8560
Research Site
Hidaka-shi, 350-1298
Research Site
Hiroshima, 730-8518
Research Site
Isehara-shi, 259-1193
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Kagoshima, 892-0833
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Kōtoku, 135-8550
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Kyoto, 606-8507
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Matsuyama, 791-0280
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Naha, 901-0154
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Osaka, 541-8567
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Ota-shi, 373-8550
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Sapporo, 060-8638
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Sendai, 980-8574
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Shimotsuke-shi, 329-0498
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Shinagawa-ku, 142-8666
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Shinjuku-ku, 162-8655
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Suita-shi, 565-0871
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Takasaki-shi, 370-0829
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Tsu, 514-8507
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Yokohama, 241-8515
Germany15 sites
Research Site
Augsburg, 86150
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Dresden, 01307
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Erlangen, 91054
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Essen, 45136
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Frankfurt am Main, 65929
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Freiburg im Breisgau, 79106
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Georgsmarienhütte, 49124
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Hanover, 30625
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Heilbronn, 74078
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Kiel, 24105
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Leipzig, 04103
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Mannheim, 68167
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Mönchengladbach, 41061
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Regensburg, 93053
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Ulm, 89075
Thailand10 sites
Research Site
Bangkok, 10210
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Bangkok, 10330
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Bangkok, 10400
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Bangkok, 10700
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Chiang Mai, 50200
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Dusit, 10300
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Hat Yai, 90110
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Khon Kaen, 40002
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Lampang, 52000
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Ratchathewi, 10400
Brazil9 sites
Research Site
Alfenas, 37130-000
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Blumenau, 89010-340
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Natal, 59075-740
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Porto Alegre, 90035-903
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Porto Velho, 76834-899
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São Paulo, 04014-002
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Taubaté, 12030-200
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Teresina, 64049-200
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Vitória, 29043-260
Canada9 sites
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Abbotsford British Columbia, British Columbia, V2S0C2
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Brampton, Ontario, L6R 3J7
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Chicoutimi, G7H 5H6
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Halifax, Nova Scotia, B3H 1V7
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Kelowna, British Columbia, V1Y 5L3
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Montreal, H3T 1E2
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Ottawa, Ontario, K1H 8L6
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Sherbrooke, Quebec, J1H 5N4
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Toronto, Ontario, M5B 1W8
India8 sites
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Bangalore, 560004
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Mohali, 160055
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Mysuru, 570017
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Nagpur, 440001
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New Delhi, 110075
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New Delhi, 110076
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Vadodara, 391760
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Varanasi, 221005
Spain8 sites
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Barcelona, 8035
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Granada, 18014
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Lleida, 25198
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Madrid, 28034
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Madrid, 28040
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Málaga, 29010
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Pamplona, 31008
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Santiago de Compostela, 15706
Taiwan8 sites
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Kaohsiung City, 80756
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Kaohsiung City, 83301
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Taichung, 40705
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Taichung
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Tainan, 704
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Taipei, 10002
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Taipei, 10449
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Taoyuan, 333
Argentina7 sites
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Buenos Aires, 1439
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CABA, 1414
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CABA, 1425
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CABA, C1113AAE
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CABA, C1425
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Chivilcoy, B6620LUD
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Rosario, 2000
France7 sites
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Bobigny, 93000
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Limoges, 87042
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Lyon, 69008
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Plérin, 22190
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Rouen, 76021
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Saint-Herblain, 44805
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Villejuif, 94805
Italy7 sites
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Bologna, 40138
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Florence, 50141
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Misterbianco, 95045
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Naples, 80131
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Padova, 35128
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Prato, 59100
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Roma, 00168
Malaysia7 sites
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George Town, 10350
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Kuala Lumpur, 50586
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Kuala Lumpur, 59100
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Kuala Selangor, 46050
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Kuala Selangor, 62250
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Kuching, 93586
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Pulau Pinang, 10450
South Korea7 sites
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Goyang-si, 10408
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Seoul, 02841
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Seoul, 03080
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Seoul, 03722
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Seoul, 06273
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Seoul, 06351
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Seoul, 5505
Turkey (Türkiye)6 sites
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Ankara, 6100
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Antalya, 07070
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Cordaleo, 35575
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Goztepe Istanbul
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Malatya, 44280
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Samsun, 55200
Vietnam6 sites
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Can Tho, 900000
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Hanoi, 100000
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Hồ Chí Minh, 700000
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Ho Chi Minh City, 700000
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Ho Chi Minh City, 70000
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Vinh, 460000
Belgium5 sites
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Brasschaat, 2930
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Brussels, 1200
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Edegem, 2650
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Haine-Saint-Paul, 7100
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Leuven, 3000
United Kingdom5 sites
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Guildford, CU2 7XX
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London, SE1 9RT
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Londonderry, BT47 6SB
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Taunton, TA1 5DA
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York, YO21 8HE
Denmark4 sites
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Aalborg, 9000
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Aarhus N, 8200
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Hillerød, 3400
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Odense, 5000
Australia3 sites
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Darlinghurst, 2010
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Nedlands, 6009
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Waratah, 2298
Poland3 sites
Research Site
Bydgoszcz, 85-796
Research Site
Krakow, 31-501
Research Site
Warsaw, 02-781
About this study
Official title: 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)
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)
Read the detailed description
This Phase Ib/III study (CAPItello-292) aims to evaluate the efficacy, safety and the degree of added benefit of capivasertib combined with CDK4/6i and fulvestrant in participants with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer. Although the dosing regimens of capivasertib + fulvestrant and of CDK4/6i + fulvestrant are established separately, the dose and schedule for the triplet combinations (capivasertib + CDK4/6i + fulvestrant) need to be confirmed. Therefore, the initial dose finding Phase Ib part of the study will determine the recommended Phase III doses (RP3D) of the triplet combinations. The Phase III part of the study will evaluate the efficacy, safety and the degree of added benefit of the triplet combinations of capivasertib and fulvestrant with investigator's choice of CDK4/6i (either palbociclib or ribociclib at safe and tolerable doses, once identified) in comparison with a control arm (fulvestrant + investigator's choice of CDK4/6i [palbociclib or ribociclib]) in a ER+ HER2- maC high risk population that did not receive prior endocrine therapy in the advanced setting.
- Being tested
- Capivasertib, Fulvestrant, Palbociclib, Ribociclib, Abemaciclib
- Keywords
- Locally advanced (inoperable) or Metastatic Breast Cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapivasertibDrug
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
FulvestrantDrug
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
PalbociclibDrug
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.
RibociclibDrug
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.
AbemaciclibDrug
Phase Ib: 50 mg/ 100 mg/ 150 mg. Twice daily for 28 consecutive days to comprise a complete 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Capivasertib Plus Palbociclib and Fulvestrant | Experimental | Capivasertib Plus Palbociclib and Fulvestrant (Ph 1b) Receives: Drug: Capivasertib; Drug: Fulvestrant; Drug: Palbociclib |
| Capivasertib Plus Ribociclib and Fulvestrant | Experimental | Capivasertib Plus Ribociclib and Fulvestrant (Ph 1b) Receives: Drug: Ribociclib |
| Capivasertib Plus Abemaciclib and Fulvestrant | Experimental | Capivasertib Plus Abemaciclib and Fulvestrant (Ph 1b) Receives: Drug: Abemaciclib |
| Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) | Experimental | Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III) Receives: Drug: Capivasertib |
| Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) | Active comparator | Fulvestrant and investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III) Receives: Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 47 months.
Secondary outcomes (22)
Phase Ib: 1. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmax.
Maximum observed plasma (peak) drug concentration.
Measured: 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.
Partial area under the plasma concentration-time curve from zero to 72 hours post-dose.
Measured: Cycle 0 (Cycle 0 is 3 days).
Phase Ib: 3. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-24h.
Partial area under the plasma concentration-time curve from zero to 24 hours post-dose.
Measured: 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.
Minimum observed plasma drug concentration.
Measured: 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.
Maximum observed plasma (peak) drug concentration.
Measured: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).
Phase Ib: 6. PK parameters for capivasertib: AUC0-12h.
Partial area under the plasma concentration-time curve from zero to 12 hours post-dose.
Measured: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).
Phase Ib: 7. PK parameters for capivasertib: Cmin.
Minimum observed plasma drug concentration.
Measured: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).
Phase Ib: 8. Objective Response Rate (ORR).
Objective Response Rate (ORR) is defined as the proportion of patients with measurable disease at baseline who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator at local site per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Measured: Up to approximately 36 months.
Phase Ib: 9. Clinical Benefit Rate (CBR) at 24 weeks.
Clinical Benefit Rate (CBR) 24 weeks is defined as the percentage of patients who have a CR or PR or who have SD per RECIST v1.1 as assessed by the investigator at local site for at least 23 weeks after date of first dose.
Measured: Up to approximately 36 months.
Phase Ib: 10. Duration of Response (DoR).
Duration of Response (DoR) will be defined as the time from the date of first documented confirmed response until date of documented progression per RECIST v1.1 as assessed by the investigator at local site or death due to any cause.
Measured: Up to approximately 36 months.
Phase Ib: 11. Progression Free Survival (PFS).
Progression Free Survival (PFS) is defined as time from date of first dose until progression per RECIST v1.1. as assessed by the investigator at local site or death due to any cause.
Measured: Up to approximately 36 months.
Phase III: 1. Overall Survival (OS).
Overall survival (OS) - time from randomization until the date of death due to any cause, secondary outcome measure in participants with HR+/HER2- locally advanced or metastatic breast cancer with gene alteration in PIK3CA/AKT1/PTEN - altered population, confirmed non-altered population and overall population.
Measured: Up to approximately 69 months.
Phase III: 2. Objective Response Rate (ORR).
Objective Response Rate (ORR) - the proportion of patients who have a complete or partial response, as determined by BICR per RECIST v1.1 in participants with HR+/HER2- locally advanced or metastatic breast cancer with gene alteration in PIK3CA/AKT1/PTEN - altered population, confirmed non-altered population and overall population.
Measured: Up to approximately 47 months.
Phase III: 3. Progression Free Survival 2 (PFS2)
Progression Free Survival 2 (PFS2) - time from randomization to the earliest of the progression event, after first subsequent therapy or death.
Measured: Up to approximately 69 months.
Phase III: 4. Duration of Response (DoR).
Duration of Response (DoR) - the time from the date of first documented response until the date of progression per RECIST v1.1 as assessed by BICR, or death due to any cause.
Measured: Up to approximately 47 months.
Phase III: 5. Clinical Benefit Rate (CBR) at 24 weeks.
Clinical Benefit Rate (CBR) at 24 weeks-the % of patients who have a CR or PR or who have SD per RECIST v1.1 as assessed by BICR for at least 23 weeks after randomisation.
Measured: Up to approximately 47 months.
Phase III: 6. Participant-reported physical functioning
TTD of physical functioning as measured by the physical functioning subscale of the EORTC QLQ-C30.
Measured: Up to approximately 69 months.
Phase III: 7. Participant-reported GHS/QoL in participants
TTD of GHS/QoL as measured by the GHS/QoL subscale of the EORTC QLQ-C30.
Measured: Up to approximately 69 months.
Phase III: 8. Participant-reported overall side effect bother in participants in the capivasertib arm relative to control arm
Proportion of participants experiencing different levels of overall treatment tolerability as measured by the Patient Global Impression-Treatment Tolerability (PGI-TT).
Measured: Up to approximately 69 months.
Phase III: 9. Plasma concentration of capivasertib pre- and post-dose.
Plasma concentration of capivasertib pre-, and post-dose.
Measured: Up to approximately 69 months.
Phase III: 10. The number of participants with adverse events.
Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with adverse events.
Measured: Up to approximately 69 months.
Phase III: 11. The number of participants with serious adverse events.
Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with serious adverse events.
Measured: Up to approximately 69 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2021
- Study start10 May 2021
- Primary completion1 Nov 2027 (estimated)
- Study completion14 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced (Inoperable) or Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase Ib: Open, Parallel groups allowed, recruiting up to approx. 222 participants. Phase III: open-label, randomised, recruiting approx. 794 participants.
- Masking
- None (open label)
- Enrolment
- 893 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04862663
- Sponsor's protocol ID
- D361DC00001
- Other IDs
- 2020-004637-20
- Acronym
- CAPItello-292
- Status last verified
- Aug 2026
- First submitted
- 17 Mar 2021
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04862663
- Acronym / sponsor ID
- CAPItello-292 / D361DC00001
- Keywords
- Locally advanced (inoperable) or Metastatic Breast Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 893 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 10 May 2021 (actual)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 14 Aug 2029 (estimated)
- First posted
- 28 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Detailed description
This Phase Ib/III study (CAPItello-292) aims to evaluate the efficacy, safety and the degree of added benefit of capivasertib combined with CDK4/6i and fulvestrant in participants with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer. Although the dosing regimens of capivasertib + fulvestrant and of CDK4/6i + fulvestrant are established separately, the dose and schedule for the triplet combinations (capivasertib + CDK4/6i + fulvestrant) need to be confirmed. Therefore, the initial dose finding Phase Ib part of the study will determine the recommended Phase III doses (RP3D) of the triplet combinations. The Phase III part of the study will evaluate the efficacy, safety and the degree of added benefit of the triplet combinations of capivasertib and fulvestrant with investigator's choice of CDK4/6i (either palbociclib or ribociclib at safe and tolerable doses, once identified) in comparison with a control arm (fulvestrant + investigator's choice of CDK4/6i [palbociclib or ribociclib]) in a ER+ HER2- maC high risk population that did not receive prior endocrine therapy in the advanced setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- Phase Ib: Open, Parallel groups allowed, recruiting up to approx. 222 participants. Phase III: open-label, randomised, recruiting approx. 794 participants.
| Arm | Type | Receives |
|---|---|---|
| Capivasertib Plus Palbociclib and Fulvestrant | Experimental | Drug: Capivasertib, Drug: Fulvestrant, Drug: PalbociclibCapivasertib Plus Palbociclib and Fulvestrant (Ph 1b) |
| Capivasertib Plus Ribociclib and Fulvestrant | Experimental | Drug: RibociclibCapivasertib Plus Ribociclib and Fulvestrant (Ph 1b) |
| Capivasertib Plus Abemaciclib and Fulvestrant | Experimental | Drug: AbemaciclibCapivasertib Plus Abemaciclib and Fulvestrant (Ph 1b) |
| Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) | Experimental | Drug: CapivasertibCapivasertib 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 comparator | Drug: FulvestrantFulvestrant and investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapivasertibPhase 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 | Drug | Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib), Capivasertib Plus Palbociclib and Fulvestrant |
| FulvestrantPhase 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 | Drug | Capivasertib Plus Palbociclib and Fulvestrant, Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) |
| PalbociclibPhase 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. | Drug | Capivasertib Plus Palbociclib and Fulvestrant |
| RibociclibPhase 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. | Drug | Capivasertib Plus Ribociclib and Fulvestrant |
| AbemaciclibPhase Ib: 50 mg/ 100 mg/ 150 mg. Twice daily for 28 consecutive days to comprise a complete 28-day cycle | Drug | Capivasertib Plus Abemaciclib and Fulvestrant |
Primary outcome
Phase Ib: 1. The number of participants with dose-limiting toxicity, as defined in the protocol.
Time frame: Within the first 28 day cycle.
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.
Phase Ib: 2. The number of participants with treatment-related adverse events.
Time frame: From baseline up to approximately 36 months.
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.
Phase Ib: 3. The number of participants with treatment-related serious adverse events.
Time frame: From baseline up to approximately 36 months.
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.
Phase III: 1. Progression Free Survival (PFS).
Time frame: Up to approximately 47 months.
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.
22 secondary outcomes
Phase Ib: 1. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmax.
Time frame: 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.
Time frame: Cycle 0 (Cycle 0 is 3 days).
Phase Ib: 3. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-24h.
Time frame: 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.
Time frame: 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.
Time frame: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).
Phase Ib: 6. PK parameters for capivasertib: AUC0-12h.
Time frame: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).
Phase Ib: 7. PK parameters for capivasertib: Cmin.
Time frame: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).
Phase Ib: 8. Objective Response Rate (ORR).
Time frame: Up to approximately 36 months.
Phase Ib: 9. Clinical Benefit Rate (CBR) at 24 weeks.
Time frame: Up to approximately 36 months.
Phase Ib: 10. Duration of Response (DoR).
Time frame: Up to approximately 36 months.
Phase Ib: 11. Progression Free Survival (PFS).
Time frame: Up to approximately 36 months.
Phase III: 1. Overall Survival (OS).
Time frame: Up to approximately 69 months.
Phase III: 2. Objective Response Rate (ORR).
Time frame: Up to approximately 47 months.
Phase III: 3. Progression Free Survival 2 (PFS2)
Time frame: Up to approximately 69 months.
Phase III: 4. Duration of Response (DoR).
Time frame: Up to approximately 47 months.
Phase III: 5. Clinical Benefit Rate (CBR) at 24 weeks.
Time frame: Up to approximately 47 months.
Phase III: 6. Participant-reported physical functioning
Time frame: Up to approximately 69 months.
Phase III: 7. Participant-reported GHS/QoL in participants
Time frame: Up to approximately 69 months.
Phase III: 8. Participant-reported overall side effect bother in participants in the capivasertib arm relative to control arm
Time frame: Up to approximately 69 months.
Phase III: 9. Plasma concentration of capivasertib pre- and post-dose.
Time frame: Up to approximately 69 months.
Phase III: 10. The number of participants with adverse events.
Time frame: Up to approximately 69 months.
Phase III: 11. The number of participants with serious adverse events.
Time frame: Up to approximately 69 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2026.
- Breast Cancer Study Locator details (for US)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
225 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Capivasertib, Fulvestrant and Palbociclib in people with Locally Advanced (Inoperable) or Metastatic Breast Cancer, run by AstraZeneca at 225 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 225 sites in United States, China, Japan, Germany, Thailand and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib: 1. The number of participants with dose-limiting toxicity, as defined in the protocol. (time frame: Within the first 28 day cycle.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.