Phase III Study of Capivasertib + Paclitaxel versus Placebo + Paclitaxel as First line Treatment for Patients with Locally Advanced or Metastatic Triple-negative Breast Cancer
- Conditions
- Triple-negative Breast CancerMedDRA version: 23.0Level: LLTClassification code 10084066Term: Triple negative breast cancer metastaticSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004687-64-SK
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 800
1. Histologically confirmed TNBC from most recenty collected tumour tissue sample
2. Metastatic or locally advanced disease; locally advanced disease most not be amenable to resection with curative intent (patient who are considered suitble 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 mixed bone lesions that can be assessed by CT or MRI in the absence of measurable disease
5. FFPE tumour sample from primary/recurrent cancer
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 640
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 160
1. Prior chemotherapy in the (neo)adjuvant setting within 12 months from the end of chemotherapy to inclusion into this study
Chemotherapy in the (neo)adjuvant setting within 6 months from the
end of chemotherapy to the date of randomization; taxane chemotherapy
in the (neo)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 following 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 half-life
(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 sensitive substrates of CYP3A4,
CYP2C9 and/or CYP2D6 with a narrow therapeutic window 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method