Clinical Trials Register

Summary
EudraCT Number:	2008-003292-42
Sponsor's Protocol Code Number:	20060534
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:	2010-03-03
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

2008-003292-42

A.3

Full title of the trial

A Phase 1b/ 2 Trial of AMG 479 or AMG 102 in Combination with Platinum-based Chemotherapy as First-Line Treatment for Extensive Stage Small Cell Lung Cancer

A.3.1

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

A Phase 1b/2 Trial of AMG 479 or AMG 102 in Combination With Platinum-based Chemotherapy as First-Line Treatment for Extensive Stage Small Cell Lung Cancer

A.4.1

Sponsor's protocol code number

20060534

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	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	Amgen Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Amgen (EUROPE) GmbH
B.5.2	Functional name of contact point	IHQ Medical Information – Clinical
B.5.3	Address:
B.5.3.1	Street Address	Dammstrasse 23, P.O. Box 1557
B.5.3.2	Town/ city	Zug
B.5.3.3	Post code	(CH-)6300
B.5.3.4	Country	Switzerland
B.5.6	E-mail	MedinfoInternational@amgen.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	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 479
D.3.2	Product code	AMG 479
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	Ganitumab
D.3.9.2	Current sponsor code	AMG 479
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	14
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.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	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	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	AMG 102
D.3.9.2	Current sponsor code	AMG 102
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	14
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.4	Route of administration of the placebo	Intravenous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
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

Previously Untreated Extensive Stage Small Cell Lung Cancer (SCLC)

E.1.1.1

Medical condition in easily understood language

Lung Cancer
Small Cell Lung Cancer
Solid Tumour
Small Cell Lung Cancer Extensive Stage

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10041067
E.1.2	Term	Small cell lung 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

Part 1:
To identify a dose of AMG 479 in combination with etoposide plus carboplatin and/or etoposide plus cisplatin and of AMG 102 in combination with etoposide plus carboplatin and/or etoposide plus cisplatin that can be administered safely and is tolerated as determined by the incidence of dose-limiting toxicity (DLT)
Part 2:
To estimate the relative treatment effect of AMG 479 (at the dose selected in Part 1) in combination with chemotherapy (etoposide plus carboplatin and/or etoposide
plus cisplatin, as determined in part 1), and of AMG 102 (at the dose selected in
Part 1) in combination with chemotherapy, compared with placebo plus
chemotherapy, as measured by the respective hazard ratios (HR) for overall survival
(OS).

E.2.2

Secondary objectives of the trial

Part 1:
To evaluate safety as assessed by the incidence of adverse events and laboratory abnormalities not defined as DLT
To evaluate safety as assessed by the incidence of anti-AMG 479 antibody formation and anti-AMG 102 antibody formation
To evaluate pharmacokinetics (PK) as assessed by the maximum observed serum concentration (Cmax) and the minimum observed serum concentration (Cmin) for AMG 479 and for AMG 102
Part 2:
To evaluate clinical benefit as assessed by the objective response rate (ORR) as measured by modified Response Evaluation Criteria in Solid Tumors (RECIST), duration of response (DOR), time to progression (TTP), progression-free survival (PFS), median OS (mOS), and OS rates at 10, 12, 24 and 36 months
To evaluate safety as assessed by the incidence of adverse events and laboratory abnormalities
For remaining secondary objectives and for exploratory objectives please see the protocol

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Disease related
• Histologically or cytologically confirmed SCLC
Extensive disease, defined by at least one of the following criteria:
− No limited disease (ie, no disease confined to the ipsilateral hemithorax, which can be safely encompassed within a tolerable radiation field)
− Extrathoracic metastases − Malignant pericardial or pleural effusion
− Contralateral hilar adenopathy
Measurable or non-measurable disease, as defined by modified RECIST (see
Appendix E)
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (see
Appendix I)
Life expectancy (with therapy) ≥ 3 months
Demographic
Woman or man ≥ 18 years old
Ethical
Before any study-specific procedure, the appropriate written informed consent must
be obtained (see Section 12.1)
Laboratory
Hematological function (within 3 days prior to enrollment), as follows:
− Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
− Platelet count ≥ 100 x 109/L
− Hemoglobin ≥ 9 g/dL
Partial thromboplastin time (PTT) ≤ 1.3 x upper limit of normal (ULN) and
international normalized ratio (INR) ≤ 1.3
Renal function, as follows:
− Creatinine (Cr) clearance (CrCl) ≥ 60 mL/minute (min); calculated by Cockcroft-
Gault formula (see Appendix D) as follows:
�� Male CrCl = (140 - age) x (weight in Kg) / (serum Cr x 72)
�� Female CrCl = (140 - age) x (weight in Kg) x 0.85 / (serum Cr x 72)
Hepatic function, as follows:
− Aspartate aminotransferase (AST) ≤ 2.5 x ULN
(≤ 5 x ULN if attributable to liver metastases)
− Alanine aminotransferase (ALT) ≤ 2.5 x ULN
(≤ 5 x ULN if attributable to liver metastases)
− Alkaline phosphatase ≤ 2.5 x ULN
(≤ 5 x ULN if attributable to bone and/or liver metastases)
− Total bilirubin ≤ 1.5 x ULN
(≤ 3 x ULN for subjects with UGT1A1 promoter polymorphism ie, Gilbert
syndrome, confirmed by genotyping or Invader UGT1A1 molecular assay prior to
enrollment)
Fasting blood glucose ≤ 160 mg/dL (Fasting will require subjects to refrain
from all food and beverage [except water] for at least 8 hours)
Negative pregnancy test (urine or serum) within 7 days prior to enrollment (women of child-bearing potential only)
General
• Plan to begin protocol specific therapy ≤ 7 days after enrollment

E.4

Principal exclusion criteria

Disease Related
Symptomatic or untreated CNS metastasis − Subjects with CNS metastases that are both treated and stably controlled are
eligible if all of the following apply:
1. therapy has been administered (surgery and/or radiation therapy);
2. there is no additional treatment planned for brain metastases;
3. the subject is clinically stable; and
4. the subject is off corticosteroids or on a stable dose of corticosteroids for at least 2 weeks prior to enrollment
Any prior or synchronous malignancy, except:
− Malignancy treated with curative intent and with no known active disease present
for ≥ 3 years prior to enrollment and felt to be at low risk for recurrence by the
treating physician
− Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
− Adequately treated cervical carcinoma in situ without evidence of disease
− Prostatic intraepithelial neoplasia without evidence of prostate cancer
Cancer Therapy • Prior chemotherapy, chemo-radiation or investigational agent for the treatment of SCLC
− Prior palliative radiotherapy to sites of distant metastasis is allowed (if completed
≥ 7 days prior to enrollment)
− Prior treatment of CNS metastasis is allowed (as defined in Section 4.2.1)
• Currently or previously treated with biological, immunological or other anti-tumor
therapies for SCLC
• Prior radiotherapy to > 25% of the bone marrow
Medications/Treatments
• Recent infection requiring systemic anti-infective treatment that was completed ≤ 14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection)
Currently being treated with full dose anti-coagulation therapy (ie coumadin
with a goal INR between 2 to 3, or full dose low molecular weight heparin)
Medical Conditions
History of bleeding diathesis
Current serious or non-healing wound or ulcer
Known positive test for human immunodeficiency virus, hepatitis C, chronic or active
hepatitis B
Any clinically significant medical or psychiatric condition, co-morbid disease,
addictive disorder, or laboratory abnormality (eg, cardiovascular disease or chronic
obstructive pulmonary disease), which may increase the risks associated with study
participation or study treatments or could interfere with the safe delivery of study
treatment or increase risk of toxicity
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
Major surgical procedure within 28 days prior to enrollment, or not yet recovered
from major surgery
Minor surgical procedures within 7 days prior to enrollment, or not yet recovered from
minor surgery
Note: uncomplicated placement of vascular access device ≥ 1 day prior to first
administration of study treatment, and fine needle aspiration, thoracocentesis
or paracentesis ≥ 3 days prior to first administration of study treatment is
acceptable
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.
General
Inability to tolerate IV drug administration
Subject is currently enrolled in or has not yet completed at least 30 days prior to
enrollment since ending other investigational device or clinical study(s)
Subject of child-bearing potential is evidently pregnant (eg, positive human chorionic
gonadotropin test) or is breast feeding
Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions ie, double barrier contraceptive methods (eg, diaphragm
plus condom), or abstinence during the course of the study and for 3 months after
the last study drug administration for women, and 6 months for men
Subject has known sensitivity to any of the products to be administered during the
study
Subject is not able to tolerate IV drug infusions
Subject unwilling or unable to comply with study requirements
Subject will not be available for follow-up assessments
Subject previously enrolled in this study

E.5 End points

E.5.1

Primary end point(s)

Part 1: ▪ The incidence of adverse events and clinical laboratory abnormalities defined as DLT
Part 2: ▪ OS

E.5.1.1

Timepoint(s) of evaluation of this end point

On treatment, 10,12 and 24 months After stopping study treatment, every 3 months for up to 36 months

E.5.2

Secondary end point(s)

Part 1
• The incidence of adverse events and laboratory abnormalities not defined as DLT :
• The incidence of anti-AMG 479 and anti-AMG 102 antibody formation
• PK (Cmax and Cmin for AMG 479 and AMG 102)
Part 2
• ORR, DOR, TTP, PFS, mOS, and OS rates at 10,12, 24, and 36 months :
• The incidence of adverse events and laboratory abnormalities
• The incidence of anti-AMG 479 and anti-AMG 102 antibody formation
• PK (Cmax and Cmin) for AMG 479 and AMG 102
• EORTC QLQ-C30 and EORTC QLQ-LC13 scores

E.5.2.1

Timepoint(s) of evaluation of this end point

10,12, 24, and 36 months

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

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 Finding

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Part 1 is open label, Part 2 is double blind placebo controlled

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.8.2.4

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

Belgium

Czech Republic

France

Hungary

India

Italy

Korea, Republic of

Netherlands

Philippines

Poland

Romania

Russian Federation

Spain

Taiwan

United Kingdom

United States

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 the clinical study will be the later of when all subjects have completed the study treatment and long term follow up (up to a maximum of 36 months from the date the last subject is randomised) or when the last subject has ended study treatment and has had the opportunity to complete the safety follow up visits.. This will allow long term assessment of disease status and survival.

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:

160

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

164

F.4.2.2

In the whole clinical trial

213

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)

Subjects who have completed 24 months of IP treatment and who continue to benefit from treatment may be eligible for continued treatment with IP by extension protocol or as provided for by the local country’s regulatory mechanism.

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

2010-04-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-04-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-02-28

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