Clinical trial NCT03997123: Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Triple Negative Breast Neoplasms
Keywords: Breast Cancer;
Triple-negative Breast Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-06-25
Enrollment: 923
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind Randomised Study
Primary purpose: TREATMENT

Brief 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)

Detailed 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)

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: The time from date of randomisation to the date of death due to any cause up to approximately 42 months
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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
measure: Investigator assessment of PFS2
timeFrame: Time from randomization to second progression or death due to any cause up to approximately 42 months
measure: Response Rate (ORR)
timeFrame: Up to approximately 42 months
measure: Safety and tolerability of drugs by assessment of AEs/SAEs
timeFrame: Up to approximately 42 months
measure: Minimum plasma concentration(Cmin), plasma concentration1-2 hours post-dose (C1-2h) and 4 hours post-dose (C4h) during months 1 and 2
timeFrame: During months 1 and 2
measure: EORTC QLQ BR23(European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer specific module)
timeFrame: approximately up to 42 months
measure: The EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items)
timeFrame: approximately up to 42 months
measure: Duration of Response (DoR)
timeFrame: Up to approximately 42 months
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 42 months
Other outcomes:
Locations:
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state: Virginia
city: Buenos Aires
country: Argentina
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city: Caba
country: Argentina
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city: Caba
country: Argentina
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city: Caba
country: Argentina
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city: Caba
country: Argentina
facility: Research Site
city: Ciudad Autonomade Buenos Aires
country: Argentina
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city: La Plata
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city: Rio de Janeiro
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city: São José do Rio Preto
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city: Victoria
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state: British Columbia
city: Kitchener
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state: Ontario
city: North York
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state: Ontario
city: Toronto
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state: Ontario
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city: Beijing
country: China
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city: Changchun
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city: Changsha
country: China
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city: Changsha
country: China
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city: Chengdu
country: China
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city: Chengdu
country: China
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city: Foshan
country: China
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city: Guangzhou
country: China
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city: Guiyang
country: China
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country: China
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city: Hangzhou
country: China
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city: Hangzhou
country: China
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country: China
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city: Harbin
country: China
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city: Hefei
country: China
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city: Jinan
country: China
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city: Linyi
country: China
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city: Nanchang
country: China
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city: Nanjing
country: China
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city: Nanyang
country: China
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city: Shanghai
country: China
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city: Shenyang
country: China
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country: China
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city: Urumqi
country: China
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city: Wenzhou
country: China
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city: Wuhan
country: China
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country: China
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city: Xi'an
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city: Zhengzhou
country: China
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city: Floridablanca
country: Colombia
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city: Ibague
country: Colombia
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city: Medellin
country: Colombia
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city: Monteria
country: Colombia
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city: Valledupar
country: Colombia
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city: Hradec Kralove
country: Czechia
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city: Olomouc
country: Czechia
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city: Praha 10
country: Czechia
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city: Praha 2
country: Czechia
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city: Brest Cedex
country: France
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city: Lyon
country: France
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country: France
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country: France
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country: France
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country: France
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city: Saint Herblain
country: France
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city: Villejuif
country: France
facility: Research Site
city: Athens
country: Greece
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city: Athens
country: Greece
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city: Athens
country: Greece
facility: Research Site
city: Heraklion
country: Greece
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city: Thessaloniki
country: Greece
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
facility: Research Site
city: Győr
country: Hungary
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city: Nyíregyháza
country: Hungary
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city: Szekszárd
country: Hungary
facility: Research Site
city: Bangalore
country: India
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city: Bangalore
country: India
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city: Gurgaon
country: India
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city: Kolkata
country: India
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country: India
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city: Mumbai
country: India
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city: Mysuru
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city: Nagpur
country: India
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city: Nashik
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city: New Delhi
country: India
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city: Bunkyo-ku
country: Japan
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city: Fukuoka-shi
country: Japan
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city: Hidaka-shi
country: Japan
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city: Hiroshima-shi
country: Japan
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city: Kagoshima-shi
country: Japan
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city: Kitaadachi-gun
country: Japan
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city: Koto-ku
country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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city: Ota-shi
country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Korea, Republic of
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city: Cheonan-si
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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city: Kuala Lumpur
country: Malaysia
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city: Kuala Lumpur
country: Malaysia
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city: Kuching
country: Malaysia
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city: Selangor
country: Malaysia
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city: Aguascalientes
country: Mexico
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city: Estado de México
country: Mexico
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country: Mexico
facility: Research Site
city: Mexico
country: Mexico
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city: Monterrey
country: Mexico
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city: Tuxtla Gutierrez
country: Mexico
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city: Tuxtla Gutierrez
country: Mexico
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city: Arequipa
country: Peru
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country: Peru
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city: Lima
country: Peru
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country: Peru
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country: Philippines
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country: Philippines
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city: Cagayan De Oro City
country: Philippines
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country: Philippines
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country: Philippines
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city: Iloilo City
country: Philippines
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city: Iloilo
country: Philippines
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city: Las Pinas
country: Philippines
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city: Legazpi City
country: Philippines
facility: Research Site
city: Manila
country: Philippines
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city: Quezon City
country: Philippines
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city: San Juan
country: Philippines
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city: Bydgoszcz
country: Poland
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city: Konin
country: Poland
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city: Poznan
country: Poland
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city: Racibórz
country: Poland
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city: Radom
country: Poland
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city: Tomaszów Mazowiecki
country: Poland
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city: Warszawa
country: Poland
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city: Wroclaw
country: Poland
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city: Lisboa
country: Portugal
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city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Saint-Petersburg
country: Russian Federation
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city: Saint-Petersburg
country: Russian Federation
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city: Volgograd
country: Russian Federation
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city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Dammam
country: Saudi Arabia
facility: Research Site
city: Jeddah
country: Saudi Arabia
facility: Research Site
city: Makkah
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
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city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Hospitalet deLlobregat
country: Spain
facility: Research Site
city: Jaén
country: Spain
facility: Research Site
city: Madrid
country: Spain
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city: Málaga
country: Spain
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city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Hsinchu
country: Taiwan
facility: Research Site
city: Hualien City
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
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city: Kaohsiung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Mueang
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Malatya
country: Turkey
facility: Research Site
city: Mersin
country: Turkey
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
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city: Surrey
country: United Kingdom
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city: York
country: United Kingdom
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Centre for Experimental Cancer Medicine (CECM), Barts Cancer Institute
name: Peter Schmid, MD,PhD,FRCP
role: PRINCIPAL_INVESTIGATOR
References: