Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292) (CAPItello-292)

May 9, 2024 updated by: AstraZeneca

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)

Study Overview

Status

Recruiting

Conditions

Locally Advanced (Inoperable) or Metastatic Breast Cancer

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

895

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: AstraZeneca Clinical Study Information Center
Phone Number: 1-877-240-9479
Email: information.center@astrazeneca.com

Study Contact Backup

Name: AZ Breast Cancer Study Navigators
Phone Number: +1-877-400-4656
Email: AstraZeneca@CareboxHealth.com

Study Locations

Argentina
- - Buenos Aires, Argentina, 1439
    - Not yet recruiting
    - Research Site
  - Buenos Aires, Argentina, C1125ABD
    - Recruiting
    - Research Site
  - Caba, Argentina, 1425
    - Recruiting
    - Research Site
  - Caba, Argentina, 1414
    - Recruiting
    - Research Site
  - Caba, Argentina, C1425
    - Recruiting
    - Research Site
  - Chivilcoy, Argentina, B6620LUD
    - Not yet recruiting
    - Research Site
  - Rosario, Argentina, 2000
    - Recruiting
    - Research Site
  - Santa Fe, Argentina, S2002RE
    - Withdrawn
    - Research Site
Australia
- - Darlinghurst, Australia, 2010
    - Recruiting
    - Research Site
  - Miranda, Australia, 2228
    - Terminated
    - Research Site
  - Nedlands, Australia, 6009
    - Active, not recruiting
    - Research Site
  - Perth, Australia, 6009
    - Recruiting
    - Research Site
  - Wahroonga, Australia, 2076
    - Recruiting
    - Research Site
  - Waratah, Australia, 2298
    - Recruiting
    - Research Site
Belgium
- - Brasschaat, Belgium, 2930
    - Not yet recruiting
    - Research Site
  - Bruxelles, Belgium, 1200
    - Not yet recruiting
    - Research Site
  - Leuven, Belgium, 3000
    - Recruiting
    - Research Site
Brazil
- - Alfenas, Brazil, 37130-000
    - Not yet recruiting
    - Research Site
  - Blumenau, Brazil, 89010-340
    - Not yet recruiting
    - Research Site
  - Natal, Brazil, 59075-740
    - Recruiting
    - Research Site
  - Porto Alegre, Brazil, 90035-903
    - Not yet recruiting
    - Research Site
  - Porto Velho, Brazil, 76834-899
    - Not yet recruiting
    - Research Site
  - São Paulo, Brazil, 04014-002
    - Not yet recruiting
    - Research Site
  - Taubaté, Brazil, 12030-200
    - Not yet recruiting
    - Research Site
  - Teresina, Brazil, 64049-200
    - Recruiting
    - Research Site
  - Vitoria, Brazil, 29043-260
    - Recruiting
    - Research Site
Canada
- - Chicoutimi, Canada, G7H 5H6
    - Recruiting
    - Research Site
  - Montreal, Canada, H3T 1E2
    - Recruiting
    - Research Site
- British Columbia
  - Abbotsford, British Columbia, Canada, V2S0C2
    - Not yet recruiting
    - Research Site
  - Kelowna, British Columbia, Canada, V1Y 5L3
    - Recruiting
    - Research Site
- Manitoba
  - Winnipeg, Manitoba, Canada, R3E 0V9
    - Not yet recruiting
    - Research Site
- New Brunswick
  - Moncton, New Brunswick, Canada, E1C 6Z8
    - Withdrawn
    - Research Site
- Nova Scotia
  - Halifax, Nova Scotia, Canada, B3H 1V7
    - Recruiting
    - Research Site
- Ontario
  - Ottawa, Ontario, Canada, K1H 8L6
    - Recruiting
    - Research Site
  - Sault Ste. Marie, Ontario, Canada, P6A 2C4
    - Withdrawn
    - Research Site
  - Toronto, Ontario, Canada, M5B 1W8
    - Not yet recruiting
    - Research Site
- Quebec
  - Sherbrooke, Quebec, Canada, J1H 5N4
    - Not yet recruiting
    - Research Site
China
- - Beijing, China, 100039
    - Not yet recruiting
    - Research Site
  - Beijing, China, 100044
    - Not yet recruiting
    - Research Site
  - Beijing, China, 100191
    - Not yet recruiting
    - Research Site
  - Beijing, China, 100210
    - Not yet recruiting
    - Research Site
  - Bengbu, China, 233060
    - Not yet recruiting
    - Research Site
  - Changchun, China, 130000
    - Not yet recruiting
    - Research Site
  - Changsha, China, 410013
    - Not yet recruiting
    - Research Site
  - Chengdu, China, 610041
    - Not yet recruiting
    - Research Site
  - Chongqing, China, 400042
    - Not yet recruiting
    - Research Site
  - Guangzhou, China, 510060
    - Not yet recruiting
    - Research Site
  - Guangzhou, China, 510062
    - Not yet recruiting
    - Research Site
  - Guangzhou, China, 510080
    - Not yet recruiting
    - Research Site
  - Hangzhou, China, 310022
    - Not yet recruiting
    - Research Site
  - Hangzhou, China, 31000
    - Not yet recruiting
    - Research Site
  - Hangzhou, China, 310016
    - Not yet recruiting
    - Research Site
  - Hefei, China, 230031
    - Not yet recruiting
    - Research Site
  - Jinan, China, 250001
    - Not yet recruiting
    - Research Site
  - Nanchang, China, 330006
    - Not yet recruiting
    - Research Site
  - Nanchang, China, 330009
    - Not yet recruiting
    - Research Site
  - Nanjing, China, 210029
    - Not yet recruiting
    - Research Site
  - Nanning, China, 530021
    - Not yet recruiting
    - Research Site
  - Shandong, China
    - Not yet recruiting
    - Research Site
  - Shanghai, China, 200032
    - Not yet recruiting
    - Research Site
  - Shenyang, China, 110001
    - Not yet recruiting
    - Research Site
  - Shenyang, China, 110016
    - Not yet recruiting
    - Research Site
  - Urumqi, China, 830000
    - Withdrawn
    - Research Site
  - Urumqi, China, 830000
    - Not yet recruiting
    - Research Site
  - Wuhan, China, 430060
    - Not yet recruiting
    - Research Site
  - Xi'an, China, 710061
    - Not yet recruiting
    - Research Site
  - Xian, China, 710100
    - Not yet recruiting
    - Research Site
  - Xiangyang City, China, 441000
    - Not yet recruiting
    - Research Site
  - Xuzhou, China, 221009
    - Not yet recruiting
    - Research Site
  - Zhengzhou, China, 450008
    - Not yet recruiting
    - Research Site
Denmark
- - Aalborg, Denmark, 9000
    - Not yet recruiting
    - Research Site
  - Aarhus N, Denmark, 8200
    - Not yet recruiting
    - Research Site
  - Hillerød, Denmark, 3400
    - Not yet recruiting
    - Research Site
  - Odense C, Denmark, 5000
    - Recruiting
    - Research Site
France
- - Bobigny, France, 93000
    - Not yet recruiting
    - Research Site
  - Clermont Ferrand, France, 63011
    - Not yet recruiting
    - Research Site
  - Limoges, France, 87042
    - Not yet recruiting
    - Research Site
  - Lyon, France, 69008
    - Not yet recruiting
    - Research Site
  - Plerin, France, 22190
    - Not yet recruiting
    - Research Site
  - Rouen, France, 76021
    - Not yet recruiting
    - Research Site
  - St Herblain, France, 44805
    - Recruiting
    - Research Site
  - Villejuif, France, 94805
    - Recruiting
    - Research Site
Germany
- - Augsburg, Germany, 86150
    - Not yet recruiting
    - Research Site
  - Berlin, Germany, 10967
    - Not yet recruiting
    - Research Site
  - Berlin, Germany, 13125
    - Not yet recruiting
    - Research Site
  - Bottrop, Germany, 46236
    - Not yet recruiting
    - Research Site
  - Dresden, Germany, 01307
    - Not yet recruiting
    - Research Site
  - Erlangen, Germany, 91054
    - Not yet recruiting
    - Research Site
  - Frankfurt, Germany, 65929
    - Not yet recruiting
    - Research Site
  - Freiburg, Germany, 79106
    - Not yet recruiting
    - Research Site
  - Georgsmarienhütte, Germany, 49124
    - Not yet recruiting
    - Research Site
  - Hamburg, Germany, 20357
    - Not yet recruiting
    - Research Site
  - Hannover, Germany, 30625
    - Not yet recruiting
    - Research Site
  - Heilbronn, Germany, 74078
    - Not yet recruiting
    - Research Site
  - Kiel, Germany, 24105
    - Not yet recruiting
    - Research Site
  - Leipzig, Germany, 04103
    - Not yet recruiting
    - Research Site
  - Mannheim, Germany, 68167
    - Not yet recruiting
    - Research Site
  - Mönchengladbach, Germany, 41061
    - Not yet recruiting
    - Research Site
  - Münster, Germany, 48149
    - Not yet recruiting
    - Research Site
  - Regensburg, Germany, 93053
    - Not yet recruiting
    - Research Site
  - Stade, Germany, 21680
    - Withdrawn
    - Research Site
  - Trier, Germany, 54290
    - Not yet recruiting
    - Research Site
  - Ulm, Germany, 89075
    - Not yet recruiting
    - Research Site
India
- - Bangalore, India, 560004
    - Recruiting
    - Research Site
  - JAipur, India, 302022
    - Recruiting
    - Research Site
  - Jaipur, India, 302017
    - Recruiting
    - Research Site
  - Mohali, India, 160055
    - Recruiting
    - Research Site
  - Mysuru, India, 570017
    - Recruiting
    - Research Site
  - Nagpur, India, 440001
    - Recruiting
    - Research Site
  - New Delhi, India, 110075
    - Recruiting
    - Research Site
  - New Delhi, India, 110076
    - Recruiting
    - Research Site
  - Pondicherry, India, 605006
    - Not yet recruiting
    - Research Site
  - Vadodara, India, 391760
    - Recruiting
    - Research Site
  - Varanasi, India, 221005
    - Recruiting
    - Research Site
Italy
- - Milan, Italy, 20141
    - Not yet recruiting
    - Research Site
  - Misterbianco, Italy, 95045
    - Not yet recruiting
    - Research Site
Japan
- - Chuo-ku, Japan, 104-0045
    - Recruiting
    - Research Site
  - Koto-ku, Japan, 135-8550
    - Recruiting
    - Research Site
Korea, Republic of
- - Goyang-si, Korea, Republic of, 10408
    - Not yet recruiting
    - Research Site
  - Seoul, Korea, Republic of, 03722
    - Recruiting
    - Research Site
  - Seoul, Korea, Republic of, 06351
    - Recruiting
    - Research Site
  - Seoul, Korea, Republic of, 02841
    - Recruiting
    - Research Site
  - Seoul, Korea, Republic of, 06273
    - Recruiting
    - Research Site
  - Seoul, Korea, Republic of, 5505
    - Recruiting
    - Research Site
  - Seoul, Korea, Republic of, 03080
    - Not yet recruiting
    - Research Site
Malaysia
- - George Town, Malaysia, 10350
    - Not yet recruiting
    - Research Site
  - Kuala Lumpur, Malaysia, 59100
    - Recruiting
    - Research Site
  - Kuala Lumpur, Malaysia, 50586
    - Not yet recruiting
    - Research Site
  - Kuala Lumpur, Malaysia, 59100
    - Not yet recruiting
    - Research Site
  - Kuching, Malaysia, 93586
    - Not yet recruiting
    - Research Site
  - Pulau Pinang, Malaysia, 10450
    - Not yet recruiting
    - Research Site
  - Selangor, Malaysia, 46050
    - Recruiting
    - Research Site
  - Selangor, Malaysia, 62250
    - Not yet recruiting
    - Research Site
Poland
- - Bydgoszcz, Poland, 85-796
    - Active, not recruiting
    - Research Site
  - Kraków, Poland, 31-501
    - Active, not recruiting
    - Research Site
  - Lodz, Poland, 91-211
    - Not yet recruiting
    - Research Site
  - Lublin, Poland, 20-090
    - Withdrawn
    - Research Site
  - Warszawa, Poland, 02-781
    - Not yet recruiting
    - Research Site
  - Warszawa, Poland, 02-781
    - Active, not recruiting
    - Research Site
Spain
- - Barcelona, Spain, 8035
    - Not yet recruiting
    - Research Site
  - Granada, Spain, 18014
    - Not yet recruiting
    - Research Site
  - Lérida, Spain, 25198
    - Not yet recruiting
    - Research Site
  - Madrid, Spain, 28040
    - Not yet recruiting
    - Research Site
  - Madrid, Spain, 28034
    - Not yet recruiting
    - Research Site
  - Madrid, Spain, 28046
    - Withdrawn
    - Research Site
  - Málaga, Spain, 29010
    - Not yet recruiting
    - Research Site
  - Pamplona, Spain, 31008
    - Not yet recruiting
    - Research Site
  - Santiago de Compostela, Spain, 15706
    - Not yet recruiting
    - Research Site
Sweden
- - Lund, Sweden, 221 85
    - Not yet recruiting
    - Research Site
  - Solna, Sweden, 17176
    - Recruiting
    - Research Site
  - Växjö, Sweden, 35185
    - Not yet recruiting
    - Research Site
Taiwan
- - Kaohsiung, Taiwan, 83301
    - Recruiting
    - Research Site
  - Kaohsiung, Taiwan, 80756
    - Not yet recruiting
    - Research Site
  - Taichung, Taiwan
    - Not yet recruiting
    - Research Site
  - Tainan, Taiwan, 704
    - Not yet recruiting
    - Research Site
  - Taipei, Taiwan, 10002
    - Not yet recruiting
    - Research Site
  - Taipei, Taiwan, 10449
    - Not yet recruiting
    - Research Site
  - Taoyuan, Taiwan, 333
    - Recruiting
    - Research Site
Thailand
- - Bangkok, Thailand, 10700
    - Not yet recruiting
    - Research Site
  - Bangkok, Thailand, 10330
    - Not yet recruiting
    - Research Site
  - Bangkok, Thailand, 10400
    - Not yet recruiting
    - Research Site
  - Bangkok, Thailand, 10210
    - Not yet recruiting
    - Research Site
  - Bangkok, Thailand, 10400
    - Withdrawn
    - Research Site
  - Chiang Mai, Thailand, 50200
    - Recruiting
    - Research Site
  - Dusit, Thailand, 10300
    - Not yet recruiting
    - Research Site
  - Hat Yai, Thailand, 90110
    - Recruiting
    - Research Site
  - Khon Kaen, Thailand, 40002
    - Recruiting
    - Research Site
  - Lampang, Thailand, 52000
    - Recruiting
    - Research Site
  - Ratchathewi, Thailand, 10400
    - Not yet recruiting
    - Research Site
Turkey
- - Ankara, Turkey, 6100
    - Recruiting
    - Research Site
  - Antalya, Turkey, 07070
    - Recruiting
    - Research Site
  - Goztepe Istanbul, Turkey
    - Recruiting
    - Research Site
  - Karsiyaka, Turkey, 35575
    - Recruiting
    - Research Site
  - Kayseri, Turkey, 38039
    - Recruiting
    - Research Site
  - Malatya, Turkey, 44280
    - Recruiting
    - Research Site
  - Samsun, Turkey
    - Recruiting
    - Research Site
United Kingdom
- - Derry, United Kingdom, BT47 6SB
    - Recruiting
    - Research Site
  - Guildford, United Kingdom, CU2 7XX
    - Not yet recruiting
    - Research Site
  - London, United Kingdom, SE1 9RT
    - Recruiting
    - Research Site
  - Taunton, United Kingdom, TA1 5DA
    - Recruiting
    - Research Site
  - York, United Kingdom, YO21 8HE
    - Recruiting
    - Research Site
United States
- Arizona
  - Tucson, Arizona, United States, 85719
    - Not yet recruiting
    - Research Site
- California
  - Los Angeles, California, United States, 90033
    - Not yet recruiting
    - Research Site
  - Los Angeles, California, United States, 90048
    - Withdrawn
    - Research Site
  - Newport Beach, California, United States, 92663
    - Not yet recruiting
    - Research Site
  - San Francisco, California, United States, 94158
    - Recruiting
    - Research Site
  - Santa Barbara, California, United States, 93105
    - Withdrawn
    - Research Site
  - Santa Rosa, California, United States, 92805
    - Recruiting
    - Research Site
- Colorado
  - Aurora, Colorado, United States, 80045
    - Recruiting
    - Research Site
- Connecticut
  - New Haven, Connecticut, United States, 06510
    - Recruiting
    - Research Site
- Delaware
  - Newark, Delaware, United States, 19713
    - Recruiting
    - Research Site
- Illinois
  - Quincy, Illinois, United States, 62305
    - Recruiting
    - Research Site
- Indiana
  - Fort Wayne, Indiana, United States, 46804
    - Not yet recruiting
    - Research Site
- Kentucky
  - Louisville, Kentucky, United States, 40202
    - Withdrawn
    - Research Site
  - Louisville, Kentucky, United States, 40202
    - Not yet recruiting
    - Research Site
- Louisiana
  - Covington, Louisiana, United States, 70433
    - Recruiting
    - Research Site
- Maryland
  - Annapolis, Maryland, United States, 21401
    - Not yet recruiting
    - Research Site
  - Baltimore, Maryland, United States, 21202
    - Recruiting
    - Research Site
  - Baltimore, Maryland, United States, 21229
    - Withdrawn
    - Research Site
- Massachusetts
  - Boston, Massachusetts, United States, 02215
    - Not yet recruiting
    - Research Site
- Michigan
  - Detroit, Michigan, United States, 48236
    - Not yet recruiting
    - Research Site
  - Grand Rapids, Michigan, United States, 49503
    - Recruiting
    - Research Site
- Missouri
  - Hannibal, Missouri, United States, 63401
    - Recruiting
    - Research Site
  - Saint Louis, Missouri, United States, 63110
    - Not yet recruiting
    - Research Site
- Nebraska
  - Omaha, Nebraska, United States, 68130
    - Recruiting
    - Research Site
- New Jersey
  - Camden, New Jersey, United States, 08103
    - Not yet recruiting
    - Research Site
- New York
  - New York, New York, United States, 10065
    - Not yet recruiting
    - Research Site
  - New York, New York, United States, 10016
    - Not yet recruiting
    - Research Site
- North Carolina
  - Durham, North Carolina, United States, 27710
    - Withdrawn
    - Research Site
- Oregon
  - Gresham, Oregon, United States, 97030
    - Not yet recruiting
    - Research Site
- Pennsylvania
  - Philadelphia, Pennsylvania, United States, 19104
    - Recruiting
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  - Pittsburgh, Pennsylvania, United States, 15213
    - Not yet recruiting
    - Research Site
  - York, Pennsylvania, United States, 17403
    - Recruiting
    - Research Site
- Rhode Island
  - Providence, Rhode Island, United States, 02903
    - Withdrawn
    - Research Site
- Tennessee
  - Nashville, Tennessee, United States, 37203
    - Recruiting
    - Research Site
- Texas
  - Dallas, Texas, United States, 75246
    - Not yet recruiting
    - Research Site
  - Fort Worth, Texas, United States, 76104
    - Not yet recruiting
    - Research Site
  - Houston, Texas, United States, 77030
    - Not yet recruiting
    - Research Site
  - San Antonio, Texas, United States, 78229
    - Recruiting
    - Research Site
  - San Antonio, Texas, United States, 78240
    - Not yet recruiting
    - Research Site
- Virginia
  - Falls Church, Virginia, United States, 22042
    - Not yet recruiting
    - Research Site
  - Leesburg, Virginia, United States, 20176
    - Not yet recruiting
    - Research Site
  - Midlothian, Virginia, United States, 23114
    - Not yet recruiting
    - Research Site
  - Norfolk, Virginia, United States, 23502
    - Not yet recruiting
    - Research Site
- Washington
  - Tacoma, Washington, United States, 98405
    - Recruiting
    - Research Site
Vietnam
- - Hanoi, Vietnam, 100000
    - Not yet recruiting
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  - Ho Chi Minh, Vietnam, 70000
    - Not yet recruiting
    - Research Site
  - Ho Chi Minh city, Vietnam, 700000
    - Recruiting
    - Research Site
  - Ho Chi Minh city, Vietnam, 700000
    - Not yet recruiting
    - Research Site
  - Vinh, Vietnam, 460000
    - Not yet recruiting
    - Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

Description

Key inclusion criteria for both phases:

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 inclusion criteria only for phase III:

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).

Key exclusion criteria for both phases:

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:
1. . diabetes mellitus type I or type II requiring insulin treatment
2. . Glycated haemoglobin (HbA1c) ≥ 8.0% (63.9 mmol/mol)
Previous allogeneic bone marrow transplant or solid organ transplant.

Key exclusion criteria for the phase III only:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Capivasertib Plus Ribociclib and Fulvestrant Capivasertib Plus Ribociclib and Fulvestrant (Ph 1b)	Drug: Ribociclib 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.
Experimental: Capivasertib Plus Abemaciclib and Fulvestrant Capivasertib Plus Abemaciclib and Fulvestrant (Ph 1b)	Drug: Abemaciclib Phase Ib: 50 mg/ 100 mg/ 150 mg. Twice daily for 28 consecutive days to comprise a complete 28-day cycle
Experimental: Capivasertib Plus Palbociclib and Fulvestrant Capivasertib Plus Palbociclib and Fulvestrant (Ph 1b)	Drug: Fulvestrant 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 Drug: Capivasertib 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 Drug: Palbociclib 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.
Experimental: Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III)	Drug: Capivasertib 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
Active Comparator: Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) Fulvestrant and investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III)	Drug: Fulvestrant 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Within the first 28 day cycle.
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.	From baseline up to approximately 36 months.
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.	From baseline up to approximately 36 months.
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. RECIST related endpoints such as PFS, ORR, DoR, CBR will be collected	Up to approximately 47 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Maximum observed plasma (peak) drug concentration.	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).	Partial area under the plasma concentration-time curve from zero to 12 hours post-dose.	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).	Minimum observed plasma drug concentration.	Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).
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).	Maximum observed plasma (peak) drug concentration.	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).	Partial area under the plasma concentration-time curve from zero to 72 hours post-dose.	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).	Partial area under the plasma concentration-time curve from zero to 24 hours post-dose.	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).	Minimum observed plasma drug concentration.	Cycle 1 Day 11 and Cycle 1 Day 14 (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.	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).	Up to approximately 36 months.
Phase Ib: 9. Clinical Benefit Rate (CBR) at 24 weeks. Time Frame: Up to approximately 36 months.	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.	Up to approximately 36 months.
Phase Ib: 10. Duration of Response (DoR). Time Frame: Up to approximately 36 months.	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.	Up to approximately 36 months.
Phase Ib: 11. Progression Free Survival (PFS). Time Frame: Up to approximately 36 months.	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.	Up to approximately 36 months.
Phase III: 1. Overall Survival (OS). Time Frame: Up to approximately 69 months.	Overall Survival (OS) - time from randomisation until the date of death due to any cause.	Up to approximately 69 months.
Phase III: 2. Objective Response Rate (ORR). Time Frame: Up to approximately 47 months.	Objective Response Rate (ORR) - the proportion of patients who have a complete or partial response), as determined by BICR per RECIST v1.1.	Up to approximately 47 months.
Phase III: 3. Duration of Response (DoR). Time Frame: Up to approximately 47 months.	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.	Up to approximately 47 months.
Phase III: 4. Clinical Benefit Rate (CBR) at 24 weeks. Time Frame: Up to approximately 47 months.	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.	Up to approximately 47 months.
Phase III: 5. Participant-reported physical functioning Time Frame: Up to approximately 69 months.	TTD of physical functioning as measured by the physical functioning subscale of the EORTC QLQ-C30.	Up to approximately 69 months.
Phase III: 6. participant-reported GHS/QoL in participants Time Frame: Up to approximately 69 months.	TTD of GHS/QoL as measured by the GHS/QoL subscale of the EORTC QLQ-C30.	Up to approximately 69 months.
Phase III: 7. Participant-reported overall side effect bother in participants in the capivasertib arm relative to control arm Time Frame: Up to approximately 69 months.	Proportion of participants experiencing different levels of overall treatment tolerability as measured by the Patient Global Impression-Treatment Tolerability (PGI-TT).	Up to approximately 69 months.
Phase III: 8. Plasma concentration of capivasertib pre- and post-dose. Time Frame: Up to approximately 69 months.	Plasma concentration of capivasertib pre-, and post-dose.	Up to approximately 69 months.
Phase III: 9. The number of participants with adverse events. Time Frame: Up to approximately 69 months.	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.	Up to approximately 69 months.
Phase III: 10. The number of participants with serious adverse events. Time Frame: Up to approximately 69 months.	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.	Up to approximately 69 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

BreastCancerStudyLocator.com

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 10, 2021

Primary Completion (Estimated)

November 1, 2027

Study Completion (Estimated)

August 14, 2029

Study Registration Dates

First Submitted

March 17, 2021

First Submitted That Met QC Criteria

April 23, 2021

First Posted (Actual)

April 28, 2021

Study Record Updates

Last Update Posted (Estimated)

May 10, 2024

Last Update Submitted That Met QC Criteria

May 9, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Locally advanced (inoperable) or Metastatic Breast Cancer

Additional Relevant MeSH Terms

Other Study ID Numbers

D361DC00001
2020-004637-20 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing 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

IPD Sharing 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

IPD Sharing Supporting Information Type

STUDY_PROTOCOL
SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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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)

Study Overview

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Intervention / Treatment

Detailed Description

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Phase

Contacts and Locations

Study Contact

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Study Locations

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Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Publications and helpful links

Helpful Links

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Estimated)

Study Completion (Estimated)

Study Registration Dates

First Submitted

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First Posted (Actual)

Study Record Updates

Last Update Posted (Estimated)

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Last Verified

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

IPD Plan Description

IPD Sharing Time Frame

IPD Sharing Access Criteria

IPD Sharing Supporting Information Type

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

Clinical Trials on Locally Advanced (Inoperable) or Metastatic Breast Cancer

Clinical Trials on Fulvestrant

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