Clinical Trials Register

Summary
EudraCT Number:	2011-005655-13
Sponsor's Protocol Code Number:	TRY
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-05-10
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

Germany - BfArM

A.2

EudraCT number

2011-005655-13

A.3

Full title of the trial

A phase II trial to evaluate safety and efficacy of combined trastuzumab and AUY922
in advanced non-small cell lung cancer (NSCLC) with HER2 - overexpression or -
amplification or - mutation.

A.3.1

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

Trastuzumab and AUY922 in HER2-aberrant NSCLC

A.3.2

Name or abbreviated title of the trial where available

TRY

A.4.1

Sponsor's protocol code number

TRY

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	University of Cologne
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Roche
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Novartis
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Hospital of Cologne
B.5.2	Functional name of contact point	Lung Cancer Group Cologne
B.5.3	Address:
B.5.3.1	Street Address	Kerpener Str. 62
B.5.3.2	Town/ city	Cologne
B.5.3.3	Post code	50937
B.5.3.4	Country	Germany
B.5.4	Telephone number	004922147887008
B.5.5	Fax number	004922147887010
B.5.6	E-mail	lungenkrebs@uk-koeln.de

D. IMP Identification
D.IMP: 1
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.2.1.1.1	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.3.9.3	Other descriptive name	rhuMAb
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	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: 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	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	AUY922
D.3.2	Product code	AUY922
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	AUY922
D.3.9.1	CAS number	747412-49-3
D.3.9.3	Other descriptive name	NVP-AUY922
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	2.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NVP-AUY922
D.3.9.3	Other descriptive name	AUY922
D.3.9.4	EV Substance Code	SUB30583
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	2.5
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.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

Advanced non-small
cell lung cancer with HER2 - overexpression or - amplification or - mutation

E.1.1.1

Medical condition in easily understood language

Lungcancer

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	10061873
E.1.2	Term	Non-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

To evaluate efficacy of combined trastuzumab and AUY922 in HER2 - overexpressed
or - amplified or - mutated NSCLC

E.2.2

Secondary objectives of the trial

• To evaluate the response rate in patients treated with trastuzumab monotherapy
• To evaluate the tolerability of trastuzumab and AUY922 in combination
(endpoints: assessment of adverse events (AEs) according to CTC-AE V4.0)
• To evaluate the clinical efficacy of trastuzumab monotherapy and the
combination descriptively (endpoints: progression-free survival (PFS), overall
survival (OS))
• To assess correlation of outcome parameters with the type of genetic aberration of
HER2 (amplification, mutation) descriptively
• To assess pharmacokinetics of AUY922 and trastuzumab
• To establish a pharmacokinetic / pharmacodynamic model with regard to
response rate and adverse events

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Stage IV NSCLC patients after failure of at least one standard therapy with HER2 protein overexpression (HER2 score 3+) or gene amplification (FISH
positive) or mutation
• Age > 18 years
• ECOG performance status 0 to 2
• Life expectancy of at least 12 weeks
• Evaluable disease or disease measurable per Response Evaluation Criteria in
Solid Tumors (RECIST)
• Adequate bone marrow, liver and renal function and adequate electrolyte
balance as assessed by the following laboratory requirements conducted at least
14 days prior to treatment:
o Hemoglobin ≥ 8.5 g/dL
o Absolute neutrophil count (ANC) ≥ 1000 / μl
o Platelet count ≥ 80,000/μL
o Total bilirubin ≤ 2 x ULN
o ALT, AST and alkaline phosphatase (AP) ≤ 2.5 x ULN
o PT-INR/PTT < 1.5 x ULN
o Creatinine clearence (CrCl) ≥ 60ml/min calculated by either MDRD-formel or
by 24 hours urine collection
o Total calcium (corrected for serum albumin) within normal limits or
correctable with supplements.
o Magnesium within lower normal limits or correctable with
supplements
• Written informed consent (after adequate explanation of the trial) to participate
in the trial and to adhere to trial procedures, as well as consenting to data
protection procedures
• In case of females with childbearing potential (definition of menopause is no
bleeding at least 12 months after last menstruation):
- negative serum pregnancy test in women with childbearing potential
- effective method of contraception (Pearl-Index not greater than 1%)

E.4

Principal exclusion criteria

• Known hypersensitivity to any study medication
• Other history of ongoing malignancy that would potentially interfere with the
interpretation of efficacy
• Previous treatment with Hsp90 inhibitors (e.g.17-AAG)
• Treatment with therapeutic doses of sodium warfarin (coumadin). Low doses
of coumadin (e.g. < 2mg/day) are permitted
• Patients with concurrent severe and/or uncontrolled medical conditions (e.g.
uncontrolled diabetes mellitus, active untreated or uncontrolled infection,
chronic obstructive or chronic restrictive pulmonary disease including
dyspnea at rest from any cause or requiring supplementary oxygen therapy)
that could cause unacceptable safety risks or compromise compliance with
the protocol
• Impaired cardiac function including any of the following:
o History (or family history) of long QT syndrome
o Mean QTc ≥ 450 msec on screening ECG
o History of clinically manifest ischemic heart disease ≤ 6 months prior
to start of the study
o History of heart failure or left ventricular (LV) dysfunction (LVEF ≤
45%) by transthoracic echocardiography
o Clinically significant ECG abnormalities including one or more of
the following: left bundle brunch block (LBBB), right bundle brunch
block (RBBB) with left anterior hemiblock (LAHB), ST segment
elevations or depressions > 1 mm or 2nd (Mobitz II) or 3rd degree AV
block
o History or presence of atrial fibrillation, atrial flutter or ventricular
arrhythmias including ventricular tachycardia or torsades de pointes
o Other clinically significant heart disease (e.g. congestive heart
failure, uncontrolled hypertension or history of unstable
hypertension)
o Clinically significant resting bradycardia (< 50 beats per minute)
o Patients who are currently receiving treatment with any medication
which has a relative risk of prolonging the QTc interval or inducing
torsades de pointes and cannot be switched or discontinued to an
alternative drug prior to commencing AUY922
o Obligate use of a cardiac pacemarker
o Angina pectoris requiring a medicinal producto Evidence of transmural infarction on ECG
o Clinically significant valvular disease
• Known diagnosis of HIV, active hepatitis B and/or C (testing is not
mandatory)
• Clinically symptomatic leptomeningeal or brain metastases (patients with
clinically stable brain metastases may be enrolled)
• Any person being in an institution on assignment of the respective authority
• Any medical, mental or psychological condition which in the opinion of the
investigator would not permit the patient to complete the study or understand
the patient information
• Any serious medical condition with organ impairment
• Parallel participation in another clinical trial
• Experimental or other therapy within the last 30 days or 5 half-life's,
whatever is of longer duration (with exception of trastuzumab, if patient is
recruited directly for combination treatment)
• Pregnancy, breast feeding

E.5 End points

E.5.1

Primary end point(s)

• Response rate
• Assessment of adverse events (AEs) according to CTC-AE V4.0
• progression-free survival (PFS), overall
survival (OS)

E.5.1.1

Timepoint(s) of evaluation of this end point

CT every 6 weeks

E.5.2

Secondary end point(s)

• Assessment of adverse events (AEs) according to CTC-AE V4.0
• progression-free survival (PFS), overall
survival (OS)
• To assess correlation of outcome parameters with the type of genetic aberration of
HER2 (amplification, mutation) descriptively
• To assess pharmacokinetics of AUY922 and trastuzumab
• To establish a pharmacokinetic / pharmacodynamic model with regard to
response rate and adverse events

E.5.2.1

Timepoint(s) of evaluation of this end point

• Every visit during the trial
• CT every 6 weeks, contact by phone every 6 months (after study discontinuation)
• Assessment of genetic type (once Screening phase) and CT every 6 mont
• PK D1, D2, D5, D8, D22, D36, after then 2 weekly
• To establish a pharmacokinetic / pharmacodynamic model with regard to
response rate and adverse events

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

E.6.11

Pharmacogenomic

Yes

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

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

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

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

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

LVLS

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:

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.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)

Standard therapy or best supportive care may be offered as well as participation in another clinical trial after discontinuation of the trial. Further treatment will be offered at the study site. The patient may nevertheless change the treating institution, if wished.

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

2012-10-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-06-09

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