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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04862663
Other study ID # D361DC00001
Secondary ID 2020-004637-20
Status Recruiting
Phase Phase 3
First received
Last updated
Start date May 10, 2021
Est. completion date August 14, 2029

Study information

Verified date June 2024
Source AstraZeneca
Contact AstraZeneca Clinical Study Information Center
Phone 1-877-240-9479
Email information.center@astrazeneca.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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)


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 895
Est. completion date August 14, 2029
Est. primary completion date November 1, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years to 99 Years
Eligibility Key inclusion criteria for both phases: 1. Adult females (pre-/peri-/ and post-menopausal), and adult males. 2. 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. 3. 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. 4. Adequate organ and bone marrow functions. 5. Consent to provide a mandatory FFPE tumour sample. Key inclusion criteria only for phase III: 1. 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. 2. Provision of mandatory blood samples at screening for central testing using an investigational ctDNA test to be stratified based on PIK3CA/AKT1/PTEN status. 3. 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. 4. 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: 1. 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. 2. Radiotherapy within 2 weeks prior to study treatment initiation. 3. Major surgery or significant traumatic injury within 4 weeks of the first dose of study treatment. 4. 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. 5. 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. 6. 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) 7. uncontrolled or high grade or symptomatic arrhythmia and atrial fibrillation 8. 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) 9. Previous allogeneic bone marrow transplant or solid organ transplant. Key exclusion criteria for the phase III only: 1. Any prior treatment with, AKT, PI3K or mTOR inhibitors. 2. 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). 3. More than 1 line of chemotherapy for metastatic disease

Study Design


Related Conditions & MeSH terms


Intervention

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
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
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.
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.
Abemaciclib
Phase Ib: 50 mg/ 100 mg/ 150 mg. Twice daily for 28 consecutive days to comprise a complete 28-day cycle

Locations

Country Name City State
Argentina Research Site Buenos Aires
Argentina Research Site Buenos Aires
Argentina Research Site Caba
Argentina Research Site Caba
Argentina Research Site Caba
Argentina Research Site Chivilcoy
Argentina Research Site Rosario
Argentina Research Site Santa Fe
Australia Research Site Darlinghurst
Australia Research Site Miranda
Australia Research Site Nedlands
Australia Research Site Perth
Australia Research Site Wahroonga
Australia Research Site Waratah
Belgium Research Site Brasschaat
Belgium Research Site Bruxelles
Belgium Research Site Edegem
Belgium Research Site Haine-Saint-Paul
Belgium Research Site Leuven
Brazil Research Site Alfenas
Brazil Research Site Blumenau
Brazil Research Site Natal
Brazil Research Site Porto Alegre
Brazil Research Site Porto Velho
Brazil Research Site São Paulo
Brazil Research Site Taubaté
Brazil Research Site Teresina
Brazil Research Site Vitoria
Canada Research Site Abbotsford British Columbia
Canada Research Site Brampton Ontario
Canada Research Site Chicoutimi
Canada Research Site Halifax Nova Scotia
Canada Research Site Kelowna British Columbia
Canada Research Site Moncton New Brunswick
Canada Research Site Montreal
Canada Research Site Ottawa Ontario
Canada Research Site Sault Ste. Marie Ontario
Canada Research Site Sherbrooke Quebec
Canada Research Site Toronto Ontario
Canada Research Site Winnipeg Manitoba
China Research Site Beijing
China Research Site Beijing
China Research Site Beijing
China Research Site Beijing
China Research Site Bengbu
China Research Site Changchun
China Research Site Changsha
China Research Site Chengdu
China Research Site Chongqing
China Research Site Guangzhou
China Research Site Guangzhou
China Research Site Guangzhou
China Research Site Hangzhou
China Research Site Hangzhou
China Research Site Hangzhou
China Research Site Hefei
China Research Site Jinan
China Research Site Nanchang
China Research Site Nanchang
China Research Site Nanjing
China Research Site Nanning
China Research Site Shandong
China Research Site Shanghai
China Research Site Shenyang
China Research Site Shenyang
China Research Site Urumqi
China Research Site Urumqi
China Research Site Wuhan
China Research Site Xi'an
China Research Site Xian
China Research Site Xiangyang City
China Research Site Xuzhou
China Research Site Zhengzhou
Denmark Research Site Aalborg
Denmark Research Site Aarhus N
Denmark Research Site Hillerød
Denmark Research Site Odense C
France Research Site Bobigny
France Research Site Clermont Ferrand
France Research Site Limoges
France Research Site Lyon
France Research Site Plerin
France Research Site Rouen
France Research Site St Herblain
France Research Site Villejuif
Germany Research Site Augsburg
Germany Research Site Berlin
Germany Research Site Berlin
Germany Research Site Bottrop
Germany Research Site Dresden
Germany Research Site Erlangen
Germany Research Site Frankfurt am Main
Germany Research Site Freiburg
Germany Research Site Georgsmarienhütte
Germany Research Site Hamburg
Germany Research Site Hannover
Germany Research Site Heilbronn
Germany Research Site Kiel
Germany Research Site Leipzig
Germany Research Site Mannheim
Germany Research Site Mönchengladbach
Germany Research Site Münster
Germany Research Site Regensburg
Germany Research Site Stade
Germany Research Site Trier
Germany Research Site Ulm
India Research Site Bangalore
India Research Site Jaipur
India Research Site JAipur
India Research Site Mohali
India Research Site Mysuru
India Research Site Nagpur
India Research Site New Delhi
India Research Site New Delhi
India Research Site Pondicherry
India Research Site Vadodara
India Research Site Varanasi
Italy Research Site Milan
Italy Research Site Misterbianco
Japan Research Site Chuo-ku
Japan Research Site Koto-ku
Korea, Republic of Research Site Goyang-si
Korea, Republic of Research Site Seoul
Korea, Republic of Research Site Seoul
Korea, Republic of Research Site Seoul
Korea, Republic of Research Site Seoul
Korea, Republic of Research Site Seoul
Korea, Republic of Research Site Seoul
Malaysia Research Site George Town
Malaysia Research Site Kuala Lumpur
Malaysia Research Site Kuala Lumpur
Malaysia Research Site Kuala Lumpur
Malaysia Research Site Kuching
Malaysia Research Site Pulau Pinang
Malaysia Research Site Selangor
Malaysia Research Site Selangor
Poland Research Site Bydgoszcz
Poland Research Site Kraków
Poland Research Site Lodz
Poland Research Site Lublin
Poland Research Site Warszawa
Poland Research Site Warszawa
Spain Research Site Barcelona
Spain Research Site Granada
Spain Research Site Lérida
Spain Research Site Madrid
Spain Research Site Madrid
Spain Research Site Madrid
Spain Research Site Málaga
Spain Research Site Pamplona
Spain Research Site Santiago de Compostela
Sweden Research Site Lund
Sweden Research Site Solna
Sweden Research Site Växjö
Taiwan Research Site Kaohsiung
Taiwan Research Site Kaohsiung
Taiwan Research Site Taichung
Taiwan Research Site Tainan
Taiwan Research Site Taipei
Taiwan Research Site Taipei
Taiwan Research Site Taoyuan
Thailand Research Site Bangkok
Thailand Research Site Bangkok
Thailand Research Site Bangkok
Thailand Research Site Bangkok
Thailand Research Site Bangkok
Thailand Research Site Chiang Mai
Thailand Research Site Dusit
Thailand Research Site Hat Yai
Thailand Research Site Khon Kaen
Thailand Research Site Lampang
Thailand Research Site Ratchathewi
Turkey Research Site Ankara
Turkey Research Site Antalya
Turkey Research Site Goztepe Istanbul
Turkey Research Site Karsiyaka
Turkey Research Site Kayseri
Turkey Research Site Malatya
Turkey Research Site Samsun
United Kingdom Research Site Derry
United Kingdom Research Site Guildford
United Kingdom Research Site London
United Kingdom Research Site Taunton
United Kingdom Research Site York
United States Research Site Annapolis Maryland
United States Research Site Aurora Colorado
United States Research Site Baltimore Maryland
United States Research Site Baltimore Maryland
United States Research Site Boston Massachusetts
United States Research Site Camden New Jersey
United States Research Site Covington Louisiana
United States Research Site Dallas Texas
United States Research Site Detroit Michigan
United States Research Site Durham North Carolina
United States Research Site Falls Church Virginia
United States Research Site Fort Wayne Indiana
United States Research Site Fort Worth Texas
United States Research Site Grand Rapids Michigan
United States Research Site Gresham Oregon
United States Research Site Hannibal Missouri
United States Research Site Houston Texas
United States Research Site Leesburg Virginia
United States Research Site Los Angeles California
United States Research Site Los Angeles California
United States Research Site Louisville Kentucky
United States Research Site Louisville Kentucky
United States Research Site Midlothian Virginia
United States Research Site Midlothian Virginia
United States Research Site Nashville Tennessee
United States Research Site New Haven Connecticut
United States Research Site New York New York
United States Research Site New York New York
United States Research Site Newark Delaware
United States Research Site Newport Beach California
United States Research Site Norfolk Virginia
United States Research Site Omaha Nebraska
United States Research Site Philadelphia Pennsylvania
United States Research Site Pittsburgh Pennsylvania
United States Research Site Providence Rhode Island
United States Research Site Quincy Illinois
United States Research Site Saint Louis Missouri
United States Research Site San Antonio Texas
United States Research Site San Antonio Texas
United States Research Site San Francisco California
United States Research Site Santa Barbara California
United States Research Site Santa Rosa California
United States Research Site Tacoma Washington
United States Research Site Tucson Arizona
United States Research Site York Pennsylvania
Vietnam Research Site Hanoi
Vietnam Research Site Ho Chi Minh
Vietnam Research Site Ho Chi Minh city
Vietnam Research Site Ho Chi Minh city
Vietnam Research Site Vinh

Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Denmark,  France,  Germany,  India,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Poland,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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.
Primary 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.
Primary 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.
Primary 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 Phase Ib: 1. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmax. 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).
Secondary 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. Cycle 0 (Cycle 0 is 3 days).
Secondary 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. Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days).
Secondary Phase Ib: 4. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmin. 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).
Secondary Phase Ib: 5. PK parameters for capivasertib: Cmax. Maximum observed plasma (peak) drug concentration. Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).
Secondary Phase Ib: 6. PK parameters for capivasertib: AUC0-12h. 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).
Secondary Phase Ib: 7. PK parameters for capivasertib: Cmin. Minimum observed plasma drug concentration. Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days).
Secondary 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). Up to approximately 36 months.
Secondary 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. Up to approximately 36 months.
Secondary 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. Up to approximately 36 months.
Secondary 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. Up to approximately 36 months.
Secondary 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. Up to approximately 69 months.
Secondary 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. Up to approximately 47 months.
Secondary 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. Up to approximately 69 months.
Secondary 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. Up to approximately 47 months.
Secondary 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. Up to approximately 47 months.
Secondary Phase III: 6. Participant-reported physical functioning TTD of physical functioning as measured by the physical functioning subscale of the EORTC QLQ-C30. Up to approximately 69 months.
Secondary 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. Up to approximately 69 months.
Secondary 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). Up to approximately 69 months.
Secondary Phase III: 9. Plasma concentration of capivasertib pre- and post-dose. Plasma concentration of capivasertib pre-, and post-dose. Up to approximately 69 months.
Secondary 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. Up to approximately 69 months.
Secondary 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. Up to approximately 69 months.
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04305496 - Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/HER2- Breast Cancer Phase 3

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