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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Jun 2019 → 22 Apr 2025

Decision date (initial)

2024-07-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB · AstraZeneca KK

External identifiers

EU CT number

2023-505009-17-00

EudraCT number

2018-004687-64

ClinicalTrials.gov

NCT03997123

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacodynamic, Therapy, Pharmacokinetic

To determine the efficacy of capivasertib + paclitaxel vs placebo + paclitaxel by OS (overall survival).

Secondary objectives 6

1. To determine the efficacy of capivasertib + paclitaxel vs placebo + paclitaxel by investigator assessment of PFS.
2. To determine the efficacy of capivasertib + paclitaxel vs placebo + paclitaxel by investigator assessment of PFS2
3. To further assess the efficacy of capivasertib + with paclitaxel versus placebo + paclitaxel by assessment of ORR, DoR, CBR
4. To evaluate the safety and tolerability of capivasertib + paclitaxel vs placebo + paclitaxel
5. To assess the impact of capivasertib + paclitaxel vs placebo + paclitaxel on patients' disease-related symptoms, physical function, and HRQoL
6. To evaluate the PK of capivasertib including the influence of intrinsic and extrinsic patient factors

Conditions and MedDRA coding

Triple-negative Breast Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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

Exclusion criteria 8

1. 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 : - 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 - Prior systematic therapy for inoperable locally advanced or metastatic disease - - 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 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 drug that are sensitive to CYP3A4, within 1 week prior to the first dose of study treatment
2. Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study treatment (capivasertib/placebo)
3. Pre-existing sensory or motor polyneuropathy ≥grade 2 according to NCI CTCAE v5 4. With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment
4. With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment
5. 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).
6. 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)
7. Inadequate bone marrow reserve or organ function at screening
8. Currently pregnant (confirmed with positive pregnancy test) or breast-feeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival

Secondary endpoints 8

1. Investigator assessment of PFS
2. Investigator assessment of PFS2
3. 3a 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).
4. 3b 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
5. 3c 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.
6. AEs/SAEs; vital signs; collection of clinical chemistry, haematology, glucose metabolism parameters; ECGs parameters.
7. Plasma PK parameters derived from a population PK model of plasma concentrations and patient factors
8. EORTC QLQ BR23 (EORTC Quality of Life Questionnaire breast cancer specific module) and EORTC QLQ C30 (EORTC Quality of Life Questionnaire Core 30 items) scale/item scores

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications