Clinical Trials Register

Summary
EudraCT Number:	2007-007107-32
Sponsor's Protocol Code Number:	M10-301
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-06-03
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

Czechia - SUKL

A.2

EudraCT number

2007-007107-32

A.3

Full title of the trial

A Phase 2 Randomized, Placebo-Controlled, Double-Blind Study of Carboplatin /Paclitaxel in Combination with ABT-869 Versus Carboplatin/Paclitaxel Alone in Subjects with Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) as First-Line Treatment

A.4.1

Sponsor's protocol code number

M10-301

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	Abbott GmbH & Co. KG
B.1.3.4	Country	Germany
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	ABT-869
D.3.2	Product code	ABT-869, A-741439.0
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.3.9.1	CAS number	796967-16-3
D.3.9.2	Current sponsor code	ABT-869, A-741439.0
D.3.9.3	Other descriptive name	1-[4-(3-Amino-1H-indazol-4-yl)phenyl]-3 -(2-fluoro-5-methylphenyl)urea
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	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)	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	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	ABT-869
D.3.2	Product code	ABT-869, A-741439.0
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.3.9.1	CAS number	796967-16-3
D.3.9.2	Current sponsor code	ABT-869, A-741439.0
D.3.9.3	Other descriptive name	1-[4-(3-Amino-1H-indazol-4-yl)phenyl]-3 -(2-fluoro-5-methylphenyl)urea
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	10
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.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	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Non small cell lung cancer.

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	10029514
E.1.2	Term	Non-small cell lung cancer NOS

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	10029515
E.1.2	Term	Non-small cell lung cancer recurrent

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	10059515
E.1.2	Term	Non-small cell lung cancer metastatic

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	10029516
E.1.2	Term	Non-small cell lung cancer stage 0

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	10029517
E.1.2	Term	Non-small cell lung cancer stage I

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	10029518
E.1.2	Term	Non-small cell lung cancer stage II

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.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10029520
E.1.2	Term	Non-small cell lung cancer stage IIIA

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.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	PT
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	PT
E.1.2	Classification code	10059515
E.1.2	Term	Non-small cell lung cancer metastatic

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	10029515
E.1.2	Term	Non-small cell lung cancer recurrent

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 assess if the addition of oral ABT-869 to carboplatin and paclitaxel can prolong progression-free survival (PFS) compared to carboplatin and paclitaxel alone in subjects with NSCLC.

E.2.2

Secondary objectives of the trial

To evaluate overall survival and other efficacy endpoints as well as the safety and tolerability of each of the treatment arms. To evaluate Quality of Life (QoL), performance status and body weight.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

At selected clinical study sites, an optional pharmacogenetic sample collection will be performed. For subjects who have signed the appropriate Informed Consent Form, DNA samples from this protocol may be used to assess the influence of genetic variants on pharmacokinetics, safety or efficacy. For example, polymorphisms in genes encode drug metabolizing enzymes (such as cytochrome P450s or uridine
glucuronosyltransferases) or drug transport proteins (such as ATP-binding cassette or solute-linked carrier proteins) may be assessed for their influence on ABT-869
pharmacokinetics. Genetic variants of potential ABT-869 targets (such as VEGF or PDGF RTKs) may also be assessed.

E.3

Principal inclusion criteria

1. The subject must be ≥ 18 years of age.
2. The subject must have cytologically or histologically confirmed non-squamous NSCLC. Subjects may have a mixed histology but must be predominantly non- squamous to be eligible.
3. The subject must have recurrent or advanced (Stage IIIb with pleural or pericardial
effusion) or metastatic (Stage IV) disease that is not amenable to surgical resection
or radiation with curative intent.
4. The subject has measurable disease, defined as at least 1 unidimensionally
measurable lesion on a computed tomography (CT) scan as defined by RECIST
(for subjects in the randomized portion only).
5. The subject has an ECOG Performance Score of 0-1.
6. The subject must have adequate bone marrow, renal and hepatic function. Please refer to section 5.2.1 of the study protocol for further information.
7. Women of childbearing potential must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study
participation and up to two months following completion of therapy.
● Total abstinence from sexual intercourse (minimum one complete menstrual
cycle);
● A vasectomized partner;
● Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration;
● Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal
ring with spermicidal jellies or cream).
Women of childbearing potential must have a negative urine pregnancy test
within 7 days prior to initiation of treatment and/or post menopausal women must
be amenorrheic for at least 12 months to be considered of non-childbearing
potential.
8. The subject is capable of understanding and complying with parameters as
outlined in the protocol and able to sign and date the informed consent approved
by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB),
prior to the initiation of any screening or study-specific procedures.

E.4

Principal exclusion criteria

1. The subject has hypersensitivity to paclitaxel or to other drugs formulated with
polyethoxylated castor oil (Cremophor).
2. The subject has received any anti-cancer therapy for treatment of NSCLC
including investigational agents, immunotherapy, traditional Chinese
medicine/herbal remedies, hormonal, "targeted" agents (i.e., erlotinib, imatinib),
biologic therapy or cytotoxic chemotherapy (i.e., alkalating agents, microtubule
inhibitors, antimetabolites).
3. Subject has received radiation therapy within 21 days of Study Day 1.
4. The subject has had major surgery within 21 days.
5. The subject has untreated brain or meningeal metastases. CT scans are not
required to rule out brain or meningeal metastases unless there is a clinical
suspicion of central nervous system disease. Subjects with treated brain
metastases that are radiographically or clinically stable for at least 4 weeks after
therapy and have no evidence of cavitation or hemorrhage in the brain lesion(s) are
eligible, providing that they are asymptomatic, and do not require corticosteroids
(must have discontinued steroids at least 1 week prior to study drug
administration).
6. The subject is receiving therapeutic anticoagulation therapy. Low dose
anticoagulation (e.g., low dose Warfarin®) for catheter prophylaxis will be
permitted.
7. The subject has a central thoracic tumor lesion as defined by location within the
hilar structures. The presence of central nodal disease is allowed.
8. The subject has proteinuria CTC Grade > 1 at baseline as measured by a UPC ratio
of > 1 and confirmed by a 24-hour urine collection.
9. The subject has a history of, or currently exhibits clinically significant cancer
related events of bleeding (e.g., gross hemoptysis defined as bright red blood of at
least ½ teaspoon or 2.5 mL per episode within 3 months prior to randomization
unless definitively treated with surgery or radiation), or the subject has a recent
history of (within 4 weeks of Study Day 1), or currently exhibits other clinically
significant signs of bleeding.
10. The subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure (BP) > 90 mm Hg or systolic BP > 140 mm Hg. Subjects may be re-screened if BP is shown to be controlled with or without intervention.
11. The subject has a history of myocardial infarction, stroke or Transient Ischemic
Attack (TIA) within 6 months of Study Day 1.
12. The subject has a documented left ventricular (LV) ejection fraction < 50%.
13. The subject has known autoimmune disease with renal involvement (i.e., lupus).
14. The subject is receiving combination anti-retroviral therapy for HIV.
15. The subject has clinically significant uncontrolled condition(s) including but not
limited to:
● Active uncontrolled infection;
● Symptomatic congestive heart failure;
● Unstable angina pectoris or cardiac arrhythmia;
● History of adrenal insufficiency; or
● Psychiatric illness/social situation that would limit compliance with study
requirements.
16. The subject has a history of another active cancer within the past 5 years except
cervical cancer in situ, in situ carcinoma of the bladder, squamous cell or basal cell
carcinoma of the skin. Questions regarding inclusion of individual subjects should
be directed to the Abbott Medical Monitor.
17. The subject has active ulcerative colitis, Crohn's disease, celiac disease or any
other conditions that interfere with absorption.
18. The subject has a medical condition, which in the opinion of the study investigator places them at an unacceptably high risk for toxicities.
19. The subject is pregnant or breast feeding.
20. The subject has NSCLC with a predominant squamous cell histology.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the study is progression-free survival (PFS). The secondary endpoints of the study are overall survival, 12-month survival rate, time to
disease progression (TTP), objective response rate, best response rate, best percent
change in tumor size, duration of response as well as the safety and tolerability of the combination. The tertiary endpoints are QoL, performance status and body weight.

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

Yes

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

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

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

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

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

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

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

The end of study is defined as the date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is longer.

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 months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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

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 2008-06-03.

Yes

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

F.4.2.2

In the whole clinical trial

120

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)

Please refer to section 5.4.1.3 of the clinical study protocol for details. Following discontinuation of the study drug, subjects will be treated in accordance with the investigator's best clinical judgement.

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

2009-07-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-07-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-04-04

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