Clinical Trials Register

Summary
EudraCT Number:	2012-002018-37
Sponsor's Protocol Code Number:	BO27938
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-02-18
Trial results	View 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

Germany - PEI

A.2

EudraCT number

2012-002018-37

A.3

Full title of the trial

A RANDOMIZED, MULTICENTER, OPEN LABEL PHASE III STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TRASTUZUMAB EMTANSINE VERSUS TRASTUZUMAB AS ADJUVANT THERAPY FOR PATIENTS WITH HER2-POSITIVE PRIMARY BREAST CANCER WHO HAVE RESIDUAL TUMOR PRESENT PATHOLOGICALLY IN THE BREAST OR AXILLARY LYMPH NODES FOLLOWING PREOPERATIVE THERAPY.

A.3.1

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

Phase III, randomized, multicenter, multinational, open label study in patients with HER2-positive primary breast cancer following neoadjuvant chemotherapy and surgery.

A.4.1

Sponsor's protocol code number

BO27938

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01772472

A.5.4

Other Identifiers

Name:	National Surgical Adjuvant Breast & Bowel Project	Number:	NSABP B-50-I
Name:	German Breast Group	Number:	GBG 77

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	F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F. Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.6	E-mail	global.rochegenentechtrials@roche.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	Yes
D.2.1.1.1	Trade name	KADCYLA®
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	trastuzumab emtansine (T-DM1)
D.3.2	Product code	RO5304020/F02
D.3.4	Pharmaceutical form	Powder for 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	trastuzumab emtansine
D.3.9.1	CAS number	1018448-65-1
D.3.9.2	Current sponsor code	RO5304020
D.3.9.3	Other descriptive name	T-DM1, Trastuzumab-MCC-DM1
D.3.9.4	EV Substance Code	SUB35467
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	160
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)	Yes
	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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	Antibody-drug conjugate comprised of a humanized monoclonal antibody (trastuzumab) and DM1.
D.IMP: 2
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.2.1.1.1	Trade name	Herceptin®
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Powder for 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	TRASTUZUMAB
D.3.9.1	CAS number	180288-69-1
D.3.9.2	Current sponsor code	RO0452317
D.3.9.4	EV Substance Code	SUB12612MIG
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	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

HER2-positive primary breast cancer.

E.1.1.1

Medical condition in easily understood language

HER2-positive primary 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	PT
E.1.2	Classification code	10065430
E.1.2	Term	HER2 positive breast cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	27.0
E.1.2	Level	LLT
E.1.2	Classification code	10027475
E.1.2	Term	Metastatic breast cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 compare the length of time it takes for the primary breast cancer to recur after treatment with preoperative chemotherapy followed by surgery between the 2 treatment arms.

E.2.2

Secondary objectives of the trial

To compare the length of time it takes for:
• the primary breast cancer to develop in other location(s)
• occurrence of secondary cancers in other organs
• death
To compare side effects of the study medication between the 2 treatment arms.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Adult patients, aged at least 18 years
• Histologically confirmed invasive breast cancer with clinical staging T1-4, N0-3, M0 (no metastasis)
• HER2-positive tumor as confirmed by central laboratory HER2 testing (immunohistochemistry and/or in-situ hybridization)
• Completion of preoperative systemic chemotherapy and HER 2 directed treatment. Systemic therapy must consist of at least 6 cycles of chemotherpay with a total duration at least 16 weeks, including at least 9 weeks of trastuzumab and at least 9 weeks of taxane based chemotherapy. Patients may have received an anthracycline as part of preoperative therapy in addition to taxane chemotherapy
• Surgical removal of all clinically-evident disease in the breast and lymph nodes
• Pathologic evidence of residual invasive carcinoma in the breast or axillary lymph nodes following completion of preoperative therapy. If invasive disease is present in both breasts, residual invasive carcinoma must be present in at least 1 breast or axillary lymph nodes postoperatively
• ECOG performance status of 0 or 1
• Life expectancy of at least 6 months from the first dose of study treatment
• Adequate organ function as determined by the following laboratory results, within 14 days prior to randomization.
• Woman of childbearing potential and men with partners of childbearing potential must be willing to use effective contraception as defined by protocol for the duration of study treatment and for at least 7 months after the last dose of study treatment.

E.4

Principal exclusion criteria

• Metastatic breast cancer
• History of any prior breast cancer except for lobular carcinoma in situ
• Treatment with a cumulative dose of epirubicin greater than 480mg/m2 or any other anthracycline like doxirubicin greater than 240mg/m2
• Treatment with any investigational anticancer drug within 28 days prior to commencing study treatment
• History of other malignancy within the previous 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome
• Peripheral neuropathy greater or equal to Grade 2
• Uncontrolled cardiopulmonary dysfunction (e.g., high blood pressure, angina, serious cardiac arrhythmia)
• Active liver disease like hepatitis
• Other current, severe, uncontrolled systemic disease (e.g., clinically significant metabolic disease, wound healing disorders, ulcers)
• For female patients, current pregnancy or lactation
• Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
• Currrent, serious, uncontrolled Infections or known infection with HIV.

E.5 End points

E.5.1

Primary end point(s)

Invasive disease-free survival (IDFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

up to 12 years

E.5.2

Secondary end point(s)

1. IDFS including second non-breast cancer
2. Disease-free survival (DFS), including second non-breast cancer or contralateral or ipsilateral ductal carcinoma in situ
3. Overall survival (OS)
4. Recurrence-free interval (RFI): time between randomization and local, regional or distant breast cancer recurrence
5. Distant recurrence-free interval (DRFI): time between randomization and distant breast cancer recurrence
6. Cardiac and overall safety: Incidence of adverse events
7. Quality of life: EORTC QLQ-C30, QLQ-BR23 and EQ-5D questionnaires.

E.5.2.1

Timepoint(s) of evaluation of this end point

1 to 6. up to 12 years
7. up to 3 years

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

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

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Quality of Life

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

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

137

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

Argentina

Colombia

Guatemala

Panama

Peru

Switzerland

Hong Kong

Taiwan

Brazil

Canada

China

Israel

Mexico

Serbia

South Africa

United Kingdom

United States

Austria

Belgium

Czechia

France

Germany

Greece

Ireland

Italy

Spain

Sweden

Türkiye

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 study will end after the last patient randomized into the study has undergone the last follow-up assessment. To enable long-term follow-up for survival and safety information, the last follow-up assessment is scheduled to occur 12 years after the first patient is randomized.

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:

1200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

284

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

207

F.4.2

For a multinational trial

F.4.2.1

In the EEA

688

F.4.2.2

In the whole clinical trial

1484

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)

The Sponsor does not intend to provide trastuzumab emtansine or other study interventions to patients after conclusion of the study or any earlier patient withdrawal.

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

2013-02-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-31

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-05-23

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