Clinical Trials Register

Summary
EudraCT Number:	2018-004687-64
Sponsor's Protocol Code Number:	D3614C00001
National Competent Authority:	Portugal - INFARMED
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-04-06
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Portugal - INFARMED

A.2

EudraCT number

2018-004687-64

A.3

Full title of the trial

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)
(CAPItello-290)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

CAPItello-290

A.4.1

Sponsor's protocol code number

D3614C00001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03997123

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca AB
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	AstraZeneca KK
B.4.2	Country	Japan
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca
B.5.2	Functional name of contact point	Clinical Study Information Centre
B.5.3	Address:
B.5.3.1	Street Address	1800 Concorde Pike
B.5.3.2	Town/ city	Wilmington
B.5.3.3	Post code	DE 19083
B.5.3.4	Country	United States
B.5.4	Telephone number	+1 877 240 9479
B.5.5	Fax number	n/an/an/an/a
B.5.6	E-mail	information.centre@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	capivasertib 200mg film coated tablet
D.3.2	Product code	AZD5363
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	capivasertib
D.3.9.1	CAS number	1143532-39-1
D.3.9.2	Current sponsor code	AZD5363
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	capivasertib 160mg film coated tablet
D.3.2	Product code	AZD5363
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	capivasertib
D.3.9.1	CAS number	1143532-39-1
D.3.9.2	Current sponsor code	AZD5363
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	160mg
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Paclitaxel 6mg/mL concentrate for solution for infusion
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	paclitaxel
D.3.9.1	CAS number	33069-62-4
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Triple-negative Breast Cancer

E.1.1.1

Medical condition in easily understood language

Breast Cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	LLT
E.1.2	Classification code	10084066
E.1.2	Term	Triple negative breast cancer metastatic
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

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

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

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

E.4

Principal exclusion criteria

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
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

E.5 End points

E.5.1

Primary end point(s)

1. Overall Survival

E.5.1.1

Timepoint(s) of evaluation of this end point

1. The time from date of randomisation to the date of death due to any cause.

E.5.2

Secondary end point(s)

1. Investigator assessment of PFS
2. Investigator assessment of PFS2
3. 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)
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
,and 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.
4. AEs/SAEs; vital signs; collection of clinical chemistry, haematology, glucose metabolism parameters; ECGs parameters.
5. Plasma PK parameters derived from a population PK model of plasma concentrations and patient factors
6. 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

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Every 8 weeks
2. Every 8 weeks following subsequent therapy post-progression
3. Every 8 weeks
4. Until study treatment discontinuation
5. During months 1 and 2.
6. Every 4 weeks until treatment discontinuation

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

paclitaxel

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Colombia

Mexico

Peru

Philippines

Saudi Arabia

Singapore

South Africa

Thailand

Turkey

Argentina

Brazil

Canada

China

Czechia

Greece

Hungary

India

Japan

Korea, Republic of

Malaysia

Poland

Portugal

Russian Federation

Slovakia

Spain

Sweden

Taiwan

United Kingdom

United States

Vietnam

France

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study is defined as the last expected visit/contact of the last patient undergoing the study (ie, 30-day follow up visit if the last patient continues treatment until progression).

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

267

F.4.2

For a multinational trial

F.4.2.1

In the EEA

267

F.4.2.2

In the whole clinical trial

800

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients are permitted to continue to receive treatment beyond the closure of the database if, in the opinion of the investigator, they are continuing to receive benefit until progression.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-08-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-08-31

P. End of Trial
P.	End of Trial Status	Completed

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