Clinical Trials Register

Summary
EudraCT Number:	2012-000660-22
Sponsor's Protocol Code Number:	BO27952
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-10-18
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2012-000660-22

A.3

Full title of the trial

A randomized, multicenter, adaptive phase II/III study to evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) versus taxane (docetaxel or paclitaxel) in patients with previously treated locally advanced or metastatic HER2-positive gastric cancer, including adenocarcinoma of the gastroesophageal junction.

A.3.1

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

A study to evaluate the efficacy and safety of trastuzumab emtansine compared to a taxane (docetaxel or paclitaxel), in patients with previously treated gastric cancer that has spread to other tissues, including adenocarcinoma of the gastroesophageal junction.

A.4.1

Sponsor's protocol code number

BO27952

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 Limited, 6 Falcon Way, Shire Park, Welwyn Garden City AL7 1TW, UK
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 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	100
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 a cytotoxic agent (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.2.5	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	Concentrate and solvent 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	DOCETAXEL
D.3.9.1	CAS number	114977-28-5
D.3.9.2	Current sponsor code	n/a
D.3.9.3	Other descriptive name	n/a
D.3.9.4	EV Substance Code	SUB12492MIG
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	20/0.5
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.3.4	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.3.9.2	Current sponsor code	n/a
D.3.9.3	Other descriptive name	n/a
D.3.9.4	EV Substance Code	SUB09583MIG
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Human Epidermal growth factor Receptor 2 (HER2) positive locally advanced or metastatic Gastric Cancer (GC), including adenocarcinoma of the gastroesophageal junction (GEJ).

E.1.1.1

Medical condition in easily understood language

Gastric cancer that has spread to other tissues.

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	17.1
E.1.2	Level	PT
E.1.2	Classification code	10066896
E.1.2	Term	HER-2 positive gastric 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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the overall survival (OS) of patients treated with
trastuzumab emtansine with the regimen from Stage 1 of the study
selected at the interim analysis to the OS of patients treated with
physician's choice of taxane (docetaxel or paclitaxel) in patients with
HER2-positive advanced gastric cancer (AGC), defined as unresectable
and locally advanced or metastatic GC, including adenocarcinoma of the
GEJ.

E.2.2

Secondary objectives of the trial

• Objective response rate (ORR)
• Progression-free survival (PFS)
• Duration of response (DOR)
• Characterization of clinical safety
• Assessment of Quality of Life

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Adult patients, aged >/= 18 years.
• ECOG performance status of 0 or 1.
• Life expectancy of at least 12 weeks from the first dose of study
treatment.
• Measurable and/or evaluable disease based on Response Evaluation
Criteria in Solid Tumors (RECIST v1.1).
• Adequate organ function as determined by the following laboratory
results, within 28 days prior to randomization.
• Patients must have a history of advanced gastric cancer (AGC), defined as unresectable and locally advanced or metastatic gastric cancer,
including adenocarcinoma of the gastroesophageal junction (GEJ), and
must have experienced disease progression during or after first-line
therapy for their disease.
• HER2-positive tumor (primary tumor or metastatic lesion) as
confirmed by central laboratory HER2 testing (immunohistochemistry
and/or in-situ hybridization).
• Patients must have received at least one prior chemotherapy regimen
for AGC; prior therapy does not need to have included HER2-directed
therapy.
• First-line therapy for AGC, including adenocarcinoma of the GEJ, must
have included a combination of at least a platinum- and a
fluoropyrimidine-based treatment given concurrently; prior therapy does
not need to have included a HER2-directed therapy.
• Adjuvant or neoadjuvant therapy for AGC is allowed.
• Women of childbearing potential and men with partners of
childbearing potential must be willing to use a highly effective, nonhormonal
form of contraception or two effective forms of contraception
by the patient and/or partner and continue its use for the duration of
study treatment and for 7 months after the last dose of study treatment.

E.4

Principal exclusion criteria

• An interval shorter than 21 days from the last dose of chemotherapy or
HER2-directed therapy until the time of randomization.
• Prior treatment with trastuzumab emtansine, docetaxel, or paclitaxel
either as single agents or as part of a treatment regimen.
• Treatment with any investigational anticancer drug within 21 days of
the first study treatment administration.
• More than one prior line of therapy for advanced gastric cancer.
• 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.
• Brain metastases that are untreated or symptomatic or require any
radiation, surgery, or steroid therapy to control symptoms from brain
metastases within 1 month of randomization.
• Peripheral neuropathy Grade >/=2.
• Uncontrolled cardiopulmonary dysfunction (e.g., high blood pressure,
serious cardiac arrhythmia).
• Other current, severe, uncontrolled systemic disease (e.g., clinically
significant metabolic disease, wound healing disorders, ulcers).
• Clinically significant bleeding within 30 days before enrollment.
• 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.
• Infection with HIV or hepatitis B virus, hepatitis C virus.

E.5 End points

E.5.1

Primary end point(s)

Overall Survival (OS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Approximately 3 years

E.5.2

Secondary end point(s)

1.) Objective response rate (ORR)
2.) Progression-free survival (PFS)
3.) Duration of response (DOR)
4.) Safety: incidence of adverse events
5.) Response distribution of treatment-related symptoms as measured
by patient-reported outcome data
6.) Time to gastric cancer symptom progression as measured by the
European Organization for Research and Treatment of Cancer
questionnaire (EORTC QLQ-STO22)
7.) Quality of life as measured by the European Organization for
Research and Treatment of Cancer questionnaire (EORTC QLQ C30)
8.) Pharmacokinetics: serum concentration-time profile of trastuzumab
emtansine
9.) Pharmacokinetics: serum concentration-time profile of total
trastuzumab
10.) Pharmacokinetics: plasma concentration-time profile of DM1

E.5.2.1

Timepoint(s) of evaluation of this end point

1.) Approximately 3 years
2.) Approximately 3 years
3.) Approximately 3 years
4.) Approximately 3 years
5.) Approximately 3 years
6.) Approximately 3 years
7.) Approximately 3 years
8.) Cycle 1, Days 1, 2, 3, 4, 8, 15; Cycle 2, Day 1; Cycle 4, Day 1
9.) Cycle 1, Days 1, 2, 3, 4, 8, 15; Cycle 2, Day 1; Cycle 4, Day 1
10.) Cycle 1, Days 1, 2, 3, 4, 8, 15; Cycle 2, Day 1; Cycle 4, Day 1

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

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

Yes

E.6.13.1

Other scope of the trial description

• Objective response rate (ORR)
• Progression-free survival (PFS)
• Duration of response (DOR)

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)

Yes

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Adaptive design

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

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

Belgium

Brazil

Canada

China

Czech Republic

Finland

France

Germany

Guatemala

Hungary

Italy

Japan

Korea, Republic of

Malaysia

Mexico

Peru

Philippines

Poland

Romania

Russian Federation

Singapore

Slovakia

Spain

Taiwan

Turkey

United Kingdom

United States

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 main study is defined as the later of the following two
dates:
• The date when 83% of patients recruited into Stage 1 have died
• The date when 63% of patients recruited into Stage 2 have died
Alternatively, the study could be terminated by the Sponsor.

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:

232

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

180

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

134

F.4.2.2

In the whole clinical trial

412

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 will receive study treatment until PD, unacceptable toxicity, or study termination by the Sponsor. Following discontinuation of study treatment, patients will continue to be followed for survival.

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

2012-11-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-04-30

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