Principal Investigator
Enrollment Status
Clinical Trial ID
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)
Phase
Phase 3
Funding Agency/Sponsor
Industrial
Disease
Breast Cancer
Enrollment 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