Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC

Triple Negative Breast Neoplasms Clinical Trial

— CAPItello-290  

Official title:

A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib/+Paclitaxel vs Placebo+Paclitaxel as First-line Treatment for Patients With Locally Advanced (Inoperable) or Metastatic TNBC.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03997123
• Other study ID #: D3614C00001
• Secondary ID: 2018-004687-64
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 25, 2019
• Est. completion date: March 18, 2024

Study information

• Verified date: January 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase III Study of Capivasertib + Paclitaxel versus Placebo + Paclitaxel as First line Treatment for Patients with Locally Advanced or Metastatic Triple-negative Breast Cancer (TNBC)

Description:

A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Paclitaxel Versus Placebo + Paclitaxel as First-line Treatment for Patients with Histologically Confirmed, Locally Advanced (Inoperable) or Metastatic Triple negative Breast Cancer (TNBC)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 923
• Est. completion date: March 18, 2024
• Est. primary completion date: March 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Histologically confirmed TNBC from most recently collected tumour tissue sample

2. Metastatic or locally recurrent disease; locally recurrent disease most not be amenable to resection with curative intent (patient who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)

3. ECOG/WHO PS: 0-1

4. Measurable disease according to RECIST 1.1 and/or lytics or mixedbone lesions that can be assessed by CT or MRI in the absence of measurable disease

5. FFPE tumour sample from primary/recurrent cancer

Exclusion Criteria:

1. Prior Chemotherapy in the neoadjuvant or adjuvant setting within 6 months from the end of chemotherapy to the date of randomization; taxane chemotherapy in the neoadjuvant or adjuvant setting within 12 months from the end of chemotherapy to the start of randomization

2. Prior systematic therapy for inoperable locally advanced or metastatic disease

3. Prior treatment with any of the treatments listed below. Patients are not eligible to enter the study if they have received any of the medications specified below or are

unable to meet the cautions and restrictions:

• AKT, PI3K, and/or mTOR inhibitors
• Capivasertib in the present study (ie, any dosing with capivasertib due to previous participation in this study)
• Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks of the first dose of study treatment. A longer washout may be required for drugs with a long halflife (eg, biologics) as agreed by the sponsor
• Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort), or drugs that are sensitive to CYP3A4 inhibition within 1 week prior to the first dose of study treatment.

4. Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study treatment (capivasertib/placebo)

5. Pre-existing sensory or motor polyneuropathy =grade 2 according to NCI CTCAE v5

6. With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment

7. Any of the following cardiac criteria at screening:

• Mean resting corrected QT interval (QTc) >470 msec obtained from 3 consecutive ECGs
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for Torsades de Pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
• Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade =2
• Uncontrolled hypotension - SBP <90 mmHg and/or DBP <50 mmHg
• Cardiac ejection fraction outside institutional range of normal or <50% (whichever is higher) as measured by echocardiogram (or multiplegated acquisition [MUGA] scan if an echocardiogram cannot be performed or is inconclusive).

8. Clinically significant abnormalities of glucose metabolism as defined by any of the

following at screening:

• Patients with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment
• HbA1c =8.0% (63.9 mmol/mol)

9. Inadequate bone marrow reserve or organ function at screening

10. Currently pregnant (confirmed with positive pregnancy test) or breast-feeding

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Capivasertib
400 mg (2 oral tablets) given on an intermittent weekly dosing schedule. Dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week off-treatment within each 28-day treatment cycle. Study treatment will be continued until disease progression unless there is evidence of unacceptable toxicity, or if the patient requests to stop the study treatment.
• Paclitaxel
80 mg/m2 concentrate for solution for infusion, 3 consecutive weekly infusions of 80 mg/m2 (given on Day 1 of Weeks 1, 2, and 3), followed by 1 week off-treatment within each 28-day treatment cycle. Paclitaxel treatment will be continued for at least 6 cycles unless the patient experiences unacceptable toxicity that is attributed directly to treatment with paclitaxel.
• Placebo
Placebo: Oral tablets. 400 mg of Placebo (2 tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week offtreatment within each 28-day treatment cycle

Locations

Country	Name	City	State
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Ciudad Autonoma De Buenos Aire
Argentina	Research Site	Ciudad Autonomade Buenos Aires
Argentina	Research Site	La Plata
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Rosario
Brazil	Research Site	Barretos
Brazil	Research Site	Florianópolis
Brazil	Research Site	Goiania
Brazil	Research Site	Londrina
Brazil	Research Site	Natal
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	São José do Rio Preto
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	Kitchener	Ontario
Canada	Research Site	North York	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Victoria	British Columbia
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Foshan
China	Research Site	Guangzhou
China	Research Site	Guiyang
China	Research Site	Haikou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Hefei
China	Research Site	Jinan
China	Research Site	Linyi
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanyang
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenyang
China	Research Site	Urumqi
China	Research Site	Wenzhou
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Zhengzhou
Colombia	Research Site	Floridablanca
Colombia	Research Site	Ibague
Colombia	Research Site	Medellin
Colombia	Research Site	Monteria
Colombia	Research Site	Valledupar
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Jihlava
Czechia	Research Site	Olomouc
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 2
Czechia	Research Site	Praha 4
France	Research Site	Brest Cedex
France	Research Site	Lyon
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Nice
France	Research Site	Paris
France	Research Site	Saint Herblain
France	Research Site	Villejuif
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Heraklion
Greece	Research Site	Thessaloniki
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Szekszárd
India	Research Site	Bangalore
India	Research Site	Bangalore
India	Research Site	Gurgaon
India	Research Site	Kolkata
India	Research Site	Kolkata
India	Research Site	Mumbai
India	Research Site	Mysuru
India	Research Site	Nagpur
India	Research Site	Nagpur
India	Research Site	Nashik
India	Research Site	New Delhi
India	Research Site	New Delhi
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hidaka-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kitaadachi-gun
Japan	Research Site	Koto-ku
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Ota-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Sunto-gun
Japan	Research Site	Takasaki-shi
Japan	Research Site	Tsu-shi
Japan	Research Site	Tsukuba-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Busan-si
Korea, Republic of	Research Site	Cheonan-si
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seongnam-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	Kuala Lumpur
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuching
Malaysia	Research Site	Selangor
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Estado de México
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	Monterrey
Mexico	Research Site	Tuxtla Gutierrez
Mexico	Research Site	Tuxtla Gutierrez
Peru	Research Site	Arequipa
Peru	Research Site	Callao
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Philippines	Research Site	Bacolod
Philippines	Research Site	Baguio City
Philippines	Research Site	Cagayan De Oro City
Philippines	Research Site	Cebu City
Philippines	Research Site	Davao City
Philippines	Research Site	Iloilo
Philippines	Research Site	Iloilo City
Philippines	Research Site	Las Pinas
Philippines	Research Site	Legazpi City
Philippines	Research Site	Manila
Philippines	Research Site	Quezon City
Philippines	Research Site	San Juan
Poland	Research Site	Bydgoszcz
Poland	Research Site	Konin
Poland	Research Site	Poznan
Poland	Research Site	Racibórz
Poland	Research Site	Radom
Poland	Research Site	Tomaszów Mazowiecki
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Russian Federation	Research Site	Arkhangelsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Volgograd
Russian Federation	Research Site	Yaroslavl
Saudi Arabia	Research Site	Dammam
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Makkah
Saudi Arabia	Research Site	Riyadh
Saudi Arabia	Research Site	Riyadh
Saudi Arabia	Research Site	Riyadh
Saudi Arabia	Research Site	Riyadh
Slovakia	Research Site	Bratislava
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Pretoria
South Africa	Research Site	Pretoria
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Hospitalet deLlobregat
Spain	Research Site	Jaén
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Sweden	Research Site	Göteborg
Sweden	Research Site	Lund
Sweden	Research Site	Stockholm
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Hualien City
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taipei City
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Bangkok
Thailand	Research Site	Hat Yai
Thailand	Research Site	Mueang
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Malatya
Turkey	Research Site	Mersin
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Sheffield
United Kingdom	Research Site	Surrey
United Kingdom	Research Site	York
United States	Research Site	Austin	Texas
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Detroit	Michigan
United States	Research Site	Fairfax	Virginia
United States	Research Site	Fort Myers	Florida
United States	Research Site	Fort Worth	Texas
United States	Research Site	Harrisburg	Pennsylvania
United States	Research Site	Houston	Texas
United States	Research Site	Miami	Florida
United States	Research Site	Nashville	Tennessee
United States	Research Site	Nyack	New York
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	San Antonio	Texas
United States	Research Site	Silver Spring	Maryland
United States	Research Site	Tampa	Florida
United States	Research Site	Westwood	Kansas
United States	Research Site	Whittier	California
United States	Research Site	Whittier	California
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh city

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Brazil,  Canada,  China,  Colombia,  Czechia,  France,  Greece,  Hungary,  India,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Peru,  Philippines,  Poland,  Portugal,  Russian Federation,  Saudi Arabia,  Slovakia,  South Africa,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Overall Survival (OS)	The time from date of randomisation to the date of death due to any cause up to approximately 42 months
Secondary	Progression-Free Survival (PFS)	Progression-Free Survival by investigator assessment (in accordance with RECIST 1.1)	The time from date of randomization to the date of progression or death due to any cause, whichever occurs earlier, up to approximately 42 months
Secondary	Investigator assessment of PFS2	PFS2 - time from randomisation to second progression or death	Time from randomization to second progression or death due to any cause up to approximately 42 months
Secondary	Response Rate (ORR)	Response Rate (ORR) - percentage of patients with at least one investigator-assessed visit response of complete or partial response (as assessed by the investigator, using RECIST 1.1)	Up to approximately 42 months
Secondary	Safety and tolerability of drugs by assessment of AEs/SAEs	Graded according to the National Cancer Institute (NCI CTCAE)	Up to approximately 42 months
Secondary	Minimum plasma concentration(Cmin), plasma concentration1-2 hours post-dose (C1-2h) and 4 hours post-dose (C4h) during months 1 and 2	Plasma PK parameters derived from a population model as data permits	During months 1 and 2
Secondary	EORTC QLQ BR23(European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer specific module)	The self-administered instrument includes 23-items and yields 5 multi-item scores (body image, sexual functioning, arm symptoms, breast symptoms, and systemic therapy side effects). Items are scored on a 4-point verbal rating scale: "Not at All," "A Little," "Quite a Bit," and "Very Much". Scores are transformed to a 0 to 100 scale, where higher scores indicate better unctioning, better HRQoL, or greater level of symptom.	approximately up to 42 months
Secondary	The EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items)	5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), and global health status/QoL scale, along with 5 individual item symptom scores (appetite loss, dyspnoea, insomnia, constipation, and diarrhoea. The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual (Fayers et al. 2001). Higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales/scores represent greater symptom severity.	approximately up to 42 months
Secondary	Duration of Response (DoR)	Duration of Response (DoR) - time from the date of first documented response until date of documented progression (as assessed by the investigator, using RECIST 1.1) or death in the absence of disease progression.	Up to approximately 42 months
Secondary	Clinical Benefit Rate (CBR)	Clinical Benefit Rate (CBR) - number of patients with complete or partial response or with stable disease maintained =24 weeks (as assessed by the investigator, using RECIST 1.1) divided by the number of patients in the analysis	Up to approximately 42 months