Clinical Trials Register

Summary
EudraCT Number:	2011-001526-19
Sponsor's Protocol Code Number:	BO27798
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-09-06
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2011-001526-19

A.3

Full title of the trial

A randomized, open-label, multicenter Phase IIIb study comparing two trastuzumab dosing regimens, each in combination with cisplatin/ capecitabine chemotherapy, as first-line therapy in patients with HER2-positive metastatic gastric or gastro-esophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.

A.3.1

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

A global and multicenter Phase IIIb study comparing two trastuzumab dosing regimens, each in combination with chemotherapy (cisplatin/capecitabine), as therapy in patients with HER2-positive metastatic gastric or gastro-esophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.

A.4.1

Sponsor's protocol code number

BO27798

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01450696

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	Herceptin®
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
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.3.9.3	Other descriptive name	rhuMAb HER2, Anti-HER
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	Yes
D.3.11.13.1	Other medicinal product type	humanised IgG1 monoclonal antibody

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

Metastatic HER2-positive adenocarcinoma of the stomach or gastro-esophageal junction.

E.1.1.1

Medical condition in easily understood language

Metastatic HER2-positive adenocarcinoma of the stomach or gastro-esophageal junction.

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	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10071114
E.1.2	Term	Metastatic gastric adenocarcinoma
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	16.0
E.1.2	Level	PT
E.1.2	Classification code	10063916
E.1.2	Term	Metastatic 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

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the duration of overall survival in patients who are randomized at enrollment to treatment with one of two trastuzumab dosing regimens (loading dose of 8mg/kg) followed by either 6mg/kg or 10mg/kg maintenance doses given every 3 weeks, plus cisplatin and capecitabine.

E.2.2

Secondary objectives of the trial

• To compare the duration of overall survival (OS) in patients on the two trastuzumab treatment arms who are found to have trastuzumab Cmin values < 12 μg/mL on Cycle 1 Day 21.
• To assess trastuzumab concentrations during treatment Cycle 1 and trastuzumab Cmin(Day 21) values in additional treatment cycles through Cycle 11 (ie, pre-dose concentration before Cycle 12) or until disease progression (whatever occurs first) for the two dosing regimens.
• To evaluate the safety and tolerability of trastuzumab for the two dosing regimens.
• To compare the duration of progression-free survival (PFS) and the overall objective response rate (ORR) in patients on the two trastuzumab treatment arms who are found to have trastuzumab Cmin values < 12 μg/mL on treatment Cycle 1 Day 21.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Evaluation of the pharmacokinetics of trastuzumab administered every three weeks at two different maintenance dose levels to patients with metastatic HER2-positive gastric or gastro-esophageal junction adenocarcinoma. Protocol BO27798PK version B dated 12-Mar-2012. Objectives of the PK sub-study:
• To characterize the serum trastuzumab concentration-vs-time (C-vs-T) profiles in the study population following the initial loading dose (8 mg/kg) at Cycle 1, and the maintenance doses (6 mg/kg or 10 mg/kg q3W) at Cycles 2 and 4.
• To evaluate the accumulation of peak and trough serum trastuzumab concentrations following selected sequential doses given every three weeks, up to the projected steady-state (refer to Section 5.1.1, Table 1).
• To describe the pharmacokinetic (PK) of trastuzumab in patients with metastatic gastric/GEJ cancer and compare to previous observations in
patients with metastatic breast cancer and gastric cancer.
• To support development and refinement of an integrated population-based model for the PK disposition of trastuzumab in cancer patients, using data from multiple dosing regimens and disease types.
• To measure the HER2/Neu serum extracellular domain (ECD) concentrations pre-dose at Cycles 2, 3, 4, and 5 and to investigate the impact of HER2/Neu serum ECD on trastuzumab pharmacokinetics.

E.3

Principal inclusion criteria

1. Male or female. Age ≥ 18 years.

4. Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction with metastatic disease documented to involve at least lung or liver or both

5. Measurable disease according to RECIST 1.1. or non-measurable evaluable disease

6. At least 2 organs involved by metastatic gastric tumor (including at least lung or liver or both) in addition to the site of the primary tumor. Metastasis in distant lymph nodes, peritoneal metastasis, malignant pleural effusion, etc. count as 'organs' in this context.

7. HER2 positive (defined as either IHC3+ or IHC2+/ISH+, with ISH positivity defined as a ratio of >=2.0 of HER2 gene copy number/number of signals for CEP 17) primary or metastatic tumor, as assessed by central laboratory

8. CCR >=45 ml/min

9. ECOG PS =2

E.4

Principal exclusion criteria

1. Previous chemotherapy for locally advanced or metastatic disease

2. Prior gastrectomy

3. Prior therapy with an anti-HER2 agent and/or platinum-based chemotherapeutic agent

4. Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (e.g., patients with a jejunostomy probe, gastric or jejunostomy tubes) which may impair the ability to administer or absorb capecitabine, as capecitabine is an orally administered drug.

6. Residual relevant toxicity resulting from previous therapy

11. History of documented congestive heart failure; angina pectoris requiring medication; electrocardiogram (ECG) evidence of trans-mural myocardial infarction; poorly controlled hypertension (systolic blood pressure (BP) > 180 mmHg or diastolic BP>100 mm Hg); clinically significant valvular heart disease; or high risk uncontrollable arrhythmias

12. Baseline LVEF< 50%, documented by echocardiography, MUGA scan, or cardiac MRI.

E.5 End points

E.5.1

Primary end point(s)

The study primary endpoint will be OS duration in all randomized patients.

E.5.1.1

Timepoint(s) of evaluation of this end point

This is event driven, when approximately 379 deaths have occurred.

E.5.2

Secondary end point(s)

The secondary endpoints will be OS in patients with Cycle 1 Cmin <12 ug/ml, Pharmacokinetic analyses , safety and tolerability in the two dosing regimens; duration of progression-free survival (PFS) and the overall objective response rate (ORR) in patients who are found to have trastuzumab Cmin values < 12 μg/mL on treatment Cycle 1 Day 21.

E.5.2.1

Timepoint(s) of evaluation of this end point

This is event driven, when approximately 379 deaths have occurred.

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

overall survival (OS); progression-free survival (PFS) and the overall objective response rate (ORR)

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Standard of care (cisplatin/capecitabine chemotherapy)

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

Australia

Bosnia and Herzegovina

Brazil

Canada

Chile

China

Czech Republic

Germany

Hungary

India

Italy

Korea, Republic of

Mexico

New Zealand

Panama

Peru

Philippines

Poland

Portugal

Russian Federation

Serbia

South Africa

Spain

Turkey

Ukraine

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 study will be when the targeted number of death events for the final analysis of the primary endoint of OS (~379/400) is reached and the last patient has completed 24 months of cardiac safety follow-up from last administration of trastuzumab, or when the study is terminated by the Sponsor, whichever occurs first. Patients still receiving trastuzumab at the time of study end and who do not have PD will be provided with commercial product.

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:

263

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

142

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

130

F.4.2.2

In the whole clinical trial

406

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 still receiving trastuzumab at the time of study end and who do not have PD will be provided with commercial product.

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

2011-12-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-08

P. End of Trial
P.	End of Trial Status	Prematurely Ended

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials