Clinical Trials Register

Summary
EudraCT Number:	2007-005941-39
Sponsor's Protocol Code Number:	MK0646-007
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-10-31
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2007-005941-39

A.3

Full title of the trial

An Open Label, Randomized Phase I/IIa Trial Evaluating MK-0646 in Combination With
Erlotinib (TARCEVA™) for Patients With Recurrent Non-Small Cell Lung Cancer.

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

MK0646-007

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

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	MERCK SHARP DOHME ITALIA S.P.A.
B.1.3.4	Country	Italy
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	MK0646-007
D.3.2	Product code	MK0646
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.3.9.2	Current sponsor code	MK0646
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	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)	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	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	Information not present in EudraCT
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	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ERLOTINIB
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	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)	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	Yes
D.3.11.13.1	Other medicinal product type	Non applicabile

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	Solution for 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

Patients with recurrent NSCLC.

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	10029519
E.1.2	Term	Non-small cell lung cancer stage III

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1. To evaluate the effect of the combination of erlotinib and MK-0646 on PFS in
patients with recurrent NSCLC.
HYPOTHESIS: Administration of erlotinib in combination with MK-0646 in patients
with recurrent NSCLC results in improvement in PFS compared to patients treated with
erlotinib alone.

E.2.2

Secondary objectives of the trial

Radiological: To quantify response rate (RR) by response criteria in solid tumors
(RECIST) criteria.
2. Clinical: To determine overall survival (OS).
HYPOTHESIS: Administration of erlotinib in combination with MK-0646 in patients
with recurrent NSCLC improves RR and OS compared to patients treated with erlotinib
alone.
2.1.3 Tertiary
1. To assess the human-anti-humanized-antibody (HAHA) response to MK-0646.
2.1.4 Exploratory Objective
1. To assess the correlation of IGF-1R expression with clinical response and safety and
evaluate biomarker expression in the IGFR and EGFR signaling pathway in archival
paraffin-embedded tumor specimens by IHC and mutation analysis.
2. Phase I: To correlate pharmacokinetic parameter values for erlotinib and MK-0646
therapy with safety.
Phase II: To correlate MK-0646 trough levels with clinical response.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients must meet all of the following criteria to participate in this study:
1. Patient has histologically or cytologically documented, unresectable, locally advanced
or metastatic Stage IIIB/IV NSCLC that has relapsed after
chemotherapy/chemoradiotherapy.
2. Patient has a pre-study, diagnostic formalin fixed paraffin-embedded tumor tissue
sample available for correlative studies.
Sample is OPTIONAL in the Phase I portion of the study.
Sample is REQUIRED in the Phase II portion of the study.
3. Patient has measurable disease based on RECIST criteria.
4. Patient has had at least one systemic chemotherapy regimen for recurrent or
metastatic disease.
5. Patient is male or female, and 18 years of age on the day of signing informed
consent.
6. Patient has a performance status 0-2 on the ECOG Performance Scale.
7. Patient must have adequate organ function as indicated by the following laboratory values.
Female patient of childbearing potential has a negative serum/urine pregnancy test at
baseline,
9. Male and female patients, as well as their partners, must agree to use adequate
contraception during therapy with MK-0646 alone or in combination with erlotinib.
Note that simultaneous use of two reliable forms of contraception is recommended for
the entire study period and ending 28±2 days after the last dose of study drug.

E.4

Principal exclusion criteria

A patient meeting any of the following criteria is not eligible to participate in this study:
1. Patient who has had chemotherapy or therapeutic radiotherapy within 2 weeks, or
biological therapy such as bevacizumab (Avastin ) within 4 weeks, prior to entering
the study or who has not recovered from adverse events due to agents administered
more than 4 weeks earlier to at least grade 1 or baseline.
Patient who has received prior EGFR TKI inhibitor/anti-EGFR mAb therapy or
prior IGF-1R - TKI inhibitor/anti-IGF-1R mAb therapy.
3. Patient who has received more than 2 prior systemic chemotherapy regimens for
recurrent or metastatic disease.
4. Patient who has not completed radiotherapy with complete resolution of toxicities at
least 2 weeks prior to beginning this study.
5. Patient is currently participating or has participated in a study with an investigational
compound or device within 30 days (or 5 half-lives of the investigational compound)
of initial dosing with study drug.
6. Patients with active central nervous system (CNS) metastases and/or carcinomatous
meningitis are excluded. However, patients with CNS metastases who have
completed a course of therapy would be eligible for the study provided they are
clinically stable for 3 months prior to entry as defined as: (1) no evidence of new or
enlarging CNS metastasis (2) off steroids or on a stable dose of steroids.
7. Patient with a primary central nervous system tumor.
8. Patient has known hypersensitivity to the components of study

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of this protocol is the difference in PFS between treatment groups;

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

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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

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

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

Yes

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)

Yes

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

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

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

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2008-10-31.	Yes
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	12
F.4.2	For a multinational trial
F.4.2.1	In the EEA	58
F.4.2.2	In the whole clinical trial	68

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

2009-02-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-01-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-02-13

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