Clinical Trials Register

Summary
EudraCT Number:	2005-005484-28
Sponsor's Protocol Code Number:	20050190
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:	2007-11-07
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

2005-005484-28

A.3

Full title of the trial

A Multicenter, Open Label, Randomized Study of AMG 951 in Subjects with Previously Untreated Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Treated with Chemotherapy with or without Bevacizumab

A.4.1

Sponsor's protocol code number

20050190

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	Apo2L/TRAIL (AMG951)
D.3.2	Product code	AMG 951
D.3.4	Pharmaceutical form	Powder for 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.3.9.2	Current sponsor code	AMG 951
D.3.9.3	Other descriptive name	Apo2L/TRAIL
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	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.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	Yes
D.2.1.1.1	Trade name	Avastin
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Ltd
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	Solution for 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	Bevacizumab
D.3.9.3	Other descriptive name	Avastin
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	25
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.IMP: 3
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	Apo2L/TRAIL (AMG 951)
D.3.2	Product code	AMG 951
D.3.4	Pharmaceutical form	Powder for 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.3.9.2	Current sponsor code	AMG 951
D.3.9.3	Other descriptive name	Apo2L/TRAIL
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	300
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Subjects with Previously Untreated Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Treated with Chemotherapy with or without Bevacizumab

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10029522
E.1.2	Term	Non-small cell lung cancer stage IV

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10029521
E.1.2	Term	Non-small cell lung cancer stage IIIB

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Phase 2 Primary Objective:
To evaluate the objective response rate (CR and PR) by modified RECIST for AMG 951 at varying dose schedules in combination with carboplatin / paclitaxel + bevacizumab for subjects with NSCLC.

E.2.2

Secondary objectives of the trial

Phase 2 Secondary Objectives:
To evaluate overall response rate (CR, PR and SD), progression-free survival, time to response, duration of response, time to progression and overall survival for AMG 951 at varying dose schedules.

To evaluate the safety profile of AMG 951 at varying dose schedules.

To evaluate the formation of anti-AMG 951 antibodies.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Disease related
-Histologically or cytologically confirmed Non-Small Cell Lung Cancer (NSCLC).
Mixed tumors will be categorized by the predominant cell type unless small cell
elements are present in which case the patient is ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy.
-Subjects must have advanced NSCLC defined as stage IIIb with malignant pleural effusion or Stage IV or recurrent disease. Disease must be measurable to be included in the phase 2 study
-Planning to receive up to 6 cycles of chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (see
Appendix F)
• Life expectancy greater than 3 months

Demographic:
• ≥18 years old and of legal age for informed consent
• Subjects must sign and date a written Independent Ethics Committee (IEC)-
approved Informed Consent Form

Laboratory
• INR ≤ 1.2 and PTT ≤ ULN within 1 week prior to enrollment

E.4

Principal exclusion criteria

Disease Related:
-Prior malignancy other than NSCLC (except in situ basal cell carcinoma or in situ
cervical cancer), unless have been treated with curative intent with no evidence of disease for ≥3yrs
-Untreated or unstable central nervous system (CNS) metastases. Subjects with treated and stably controlled CNS metastases are eligible for cohorts A&B of the phase 2 part of the study if definitive therapy has been administered (surgery and/or radiation therapy), there is no planned treatment for brain metastases, and the subject is clinically stable and is off corticosteroids or on a stable dose of corticosteroids for at least 2 wks prior to enrollment
-Myocardial infarction, or unstable or uncontrolled disease or condition related to
or impacting cardiac function (e.g., unstable angina, congestive heart failure [New York Heart Association >class II]) within 1 yr of enrollment
-Uncontrolled hypertension defined as: systolic blood pressure ≥150 mm Hg OR
diastolic blood pressure ≥100mm Hg (antihypertensive therapy to achieve these
parameters is allowable)
-History of arterial thrombosis, pulmonary embolus, deep vein thrombosis or hemorrhagic disorders within 1 yr of enrollment
-Recent major surgical procedure within 28 days of enrollment
-Subjects must not have serious non-healing wound ulcer, or bone fracture within
21 days prior to enrollment
-Persistent history of gross hemoptysis (defined as bright red blood of a ½teaspoon or more) relating to subject’s NSCLC
-Known (documented in medical notes) HIV infection
-Active infection on day of enrollment
-Known to be hepatitis C positive OR hepatitis B surface antigen positive
-Subjects with Gilbert’s syndrome
Laboratory:
-Absolute neutrophil count (ANC) <1.5 x 109 /L (without granulocyte-colony stimulating factor support within 2 wks of enrollment)
-Platelet count <100 x 109 /L (without transfusion within 2 wks of enrollment)
-Hemoglobin <9 g/dL (subjects may be transfused or receive erythropoietic treatment to meet criterion)
-Urine protein quantitative value of >1+ on dipstick or ≥30 mg/dL in urinalysis. If quantitative protein is <500 mg in 24hr urine collection then subject can be included
-Significant liver dysfunction as defined by aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 x upper limits of normal (ULN)
-Alkaline phosphatase >2.5 x ULN, or alkaline phosphatase >5 x ULN in the presence of bone or liver metastasis
-Total bilirubin >1.5 X ULN
-Calculated creatinine clearance <50mL/min.
-Hypercalcemia (serum calcium ≥12.0 mg/dL or symptomatic)
Medication:
-Prior chemotherapy (except for adjuvant chemotherapy, provided the last dose of adjuvant therapy was received at least one year prior to enrollment), hormonal therapy, radiotherapy (except palliative radiotherapy for bone metastases or radiation therapy for CNS metastases) or immunotherapy for treatment of advanced NSCLC
-Prior drug treatment or therapy with investigational agents for NSCLC
-Therapeutic anticoagulation treatment. Prophylactic anticoagulation of venous access devices (e.g., with low-dose warfarin [1-2 mg/day] or lowdose heparin) is allowed providing INR ≤1.2 and PTT ≤ULN within 1 wk prior to randomization
-Chronic daily treatment with aspirin (>325 mg/day) or non-steroidal antiinflammatory agents known to inhibit platelet function. Treatment with
dipyridamole, ticlopidine, clopidogrel and/or cilostazol is also not allowed
General:
-Participation in clinical trials or undergoing other investigational procedures
within 30 dys before study enrollment
-Subject is evidently pregnant (eg, positive HCG test) or is breast feeding.
-Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions i.e. double barrier contraceptive methods (eg diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last study drug administration for women, and 1 month for men.
-Subject has known sensitivity to any of the products to be administered during
study.
-Subject has any kind of disorder that compromises the ability of the subject to
give written informed consent and/or to comply with study procedures.
-Any condition which in the investigator’s opinion makes the subject unsuitable
for study participation
-Subjects enrolled and dosed in phase 1b will be excluded from phase 2

Exclusion criteria for bevacizumab treatment (cohorts C, D and E) in
phase 2
-Subjects with central nervous system tumor involvement
-Subjects with squamous NSCLC

Subjects who have CNS tumor involvement and/or squamous NSCLC are not eligible to receive bevacizumab treatment, but are eligible to enter the phase 2 study provided they fulfill all other inc/excl criteria. These subjects will be assigned to the nonbevacizumab part (cohorts 1&2) of the phase 2 study.

E.5 End points

E.5.1

Primary end point(s)

Objective response rate (complete or partial response) (Phase 2)

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)

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)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

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

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

End of study will be defined as the date when the last subject completes the safety
follow up visit (approximately 4 weeks after the final dose of AMG 951).

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	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
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	35
F.4.2	For a multinational trial
F.4.2.1	In the EEA	200
F.4.2.2	In the whole clinical trial	200

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

2008-01-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-10-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-11-14

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