Clinical Trials Register

Summary
EudraCT Number:	2008-001605-42
Sponsor's Protocol Code Number:	20060317
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-02-10
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2008-001605-42

A.3

Full title of the trial

A Multicenter, Double-Blind, 3-Arm, Phase 1b/2 Study in Subjects with Unresectable
Locally Advanced or Metastatic Gastric or Esophagogastric Junction Adenocarcinoma to Evaluate the Safety and Efficacy of First-line Treatment with Epirubicin, Cisplatin, and Capecitabine(ECX) plus AMG 102

A.4.1

Sponsor's protocol code number

20060317

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Amgen Inc
B.1.3.4	Country	United States
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	AMG 102
D.3.2	Product code	AMG 102
D.3.4	Pharmaceutical form	Intravenous infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	AMG 102
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	30
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Intravenous infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Unrespectable locally advanced or metastatic gastric or esophagogastric unction adenocarcinoma

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10063916
E.1.2	Term	Metastatic gastric cancer

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary

Part 1 (phase 1b-open label):

• To identify safe dose levels of AMG 102, up to 15 mg/kg Q3W, to combine with
ECX.

Part 2 (phase 2-double-blind):

• To estimate with pre-specified precision the effect of the addition of AMG 102 to
ECX on the progression free survival (PFS) of previously untreated subjects with
unresectable locally advanced or metastatic gastric or esophagogastric junction
adenocarcinoma.

E.2.2

Secondary objectives of the trial

Secondary

Part 1

To evaluate the incidence of adverse events, abnormal laboratory values not defined as DLTs, and anti-AMG 102 antibody formation.
To evaluate the PK of AMG 102 (Cmax and Cmin).

Part 2

To evaluate the effect of the addition of AMG 102 to ECX on OS, response rates, time to response, duration of response, disease control rates, incidence of adverse events and laboratory abnormalities.
To evaluate the PK (Cmax and Cmin) of AMG 102, and estimate the impact of
co-administration of AMG 102 to the PK of epirubicin and cisplatin in a sub-group of
subjects at selected sites outside of Europe/Asia.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion Criteria

4.1.1 Disease related
• Pathologically confirmed unresectable locally advanced or metastatic gastric or
esophagogastric junction (EGJ) adenocarcinoma; tumors of the distal esophagus
within 5 cm of the EGJ are eligible
• ECOG performance status 0 or 1
• Life expectancy ≥ 3 months
4.1.2 Demographic
• Male or female ≥ 18 years of age
4.1.3 Ethical
• Before any study-specific procedure, the appropriate written informed consent
must be obtained (see Section 12.1)
4.1.4 Laboratory
• Hemoglobin ≥ 9 g/dL (can be post-transfusion)
• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L (without transfusion within 14 days before enrollment
or randomization)
• Creatinine clearance ≥ 60 mL/minute (calculated or measured)
• Aspartate aminotransferase (AST) and alanine amino transferase (ALT) ≤ 2.5 x
ULN (OR AST and ALT ≤ 5.0 x ULN in the presence of liver metastasis)
• Total bilirubin ≤ 1.5x ULN
• Partial thromboplastin time (PTT) ≤ 1.5 x ULN and international normalized ratio
(INR) ≤ ULN
4.1.5 General
• Plan to begin protocol specific therapy within 7 days after enrollment or
randomization
• Able to tolerate infusions and take oral medications

E.4

Principal exclusion criteria

Exclusion Criteria

4.2.1 Disease Related
• Previous systemic therapy (chemotherapy or biologic therapy) for locally
advanced or metastatic gastric or esophagogastric adenocarcinoma
• Less than 6 months have elapsed from completion of prior neoadjuvant or
adjuvant chemotherapy or chemoradiotherapy. Patients previously treated with
anthracyclines must not exceed total cumulative dose of epirubicin of 900 mg/m2
(or equivalent thereof, if a different anthracycline has been administered in the
past) including doses to be administered in this trial.
• Any prior or synchronous malignancy (except for non-melanomatous skin cancer
or in situ cervical cancer) other than the study disease, unless treated with
curative intent and having completed all therapy with no evidence of disease ≤ 5
years before enrollment or randomization
• Known peripheral neuropathy > grade 1
• Known dihydropyrimidine dehydrogenase deficiency (DPD)
• Any clinically significant medical condition other than cancer, including
cardiovascular disease or chronic obstructive pulmonary disease (COPD), which
in the opinion of the investigator would interfere with the safe delivery of study
treatment or increase risk of toxicity
• History of any medical condition that in the opinion of the investigator, may
increase the risks associated with study participation or study treatments or may
interfere with the conduct of the study or interpretation of study results
• Major surgical procedure ≤ 30 days before enrollment or randomization or not yet
recovered from prior major surgery
• Minor surgery (e,g. catheter or gastrostomy tube placement) ≤14 days before
enrollment or randomization or not yet recovered from prior minor surgery;
although placement of central venous access device, fine needle aspiration,
thoracentesis, endoscopic biliary stent or paracentesis ≥ 1 day before enrollment
or randomization is acceptable
• Subjects with resectable disease or suitable for definitive chemoradiation
• Plans for surgical resection based on response to protocol therapy
• Subjects who have persistent gastric outlet obstruction, complete dysphagia or
are dependent upon jejunostomy for feeding.
• Tumors of squamous cell histology
• Treatment with radiotherapy ≤ 14 days before enrollment or randomization
• Known central nervous system metastases
• Clinically significant upper gastro-intestinal bleeding < 30 days prior to enrollment
or randomization
4.2.2 Cardiac
• LVEF < 50% as determined by either MUGA scan or ECHO
• Clinically significant (i.e. active) cardiac disease or myocardial infarction within
the last 12 months before enrollment or randomization. Patients with any history
of clinically significant cardiac failure are excluded from study entry
4.2.3 Other abnormal medical conditions
• Serious or non-healing wound
• Known positive test for HIV, hepatitis C, chronic or active hepatitis B
• Presence of peripheral edema > Grade 2
• Thrombosis or vascular ischemic events within the last twelve months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction.

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoints:

Part 1

• The incidence of adverse events defined as DLTs

Part 2

• PFS

Secondary Endpoints:

Part 1

• Incidence of adverse events, abnormal laboratory values not defined as DLTs, and anti- AMG 102 antibody

• Cmax and Cmin of AMG 102 concentration

Part 2

• OS
• Objective response rate (complete and partial response), disease control rate, duration of
response, and time to response
• The incidence of adverse events, laboratory abnormalities, and anti-AMG102 antibody
formation.
• Cmax and Cmin of AMG 102; Cmax and AUC of epirubicin, and cisplatin when used with or without AMG 102 in a sub-group of subjects at selected sites outside of Europe/Asia.

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

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Dose De-escalation

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

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 study will occur when all subjects have died, completed the treatment period or long-term follow-up (for a maximum of 36 months from the date that the last subject was enrolled or randomized) whichever is later. The end of study for each subject is defined as the date the subject withdraws consent from the study, completes the final long-term follow-up visit, or death, whichever is earlier.

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	20
F.4.2	For a multinational trial
F.4.2.1	In the EEA	86
F.4.2.2	In the whole clinical trial	138

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

2010-04-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-03-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-06-19

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