Clinical Trials Register

Summary
EudraCT Number:	2013-004324-11
Sponsor's Protocol Code Number:	NVALT-15
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-03-12
Trial 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

Netherlands - Competent Authority

A.2

EudraCT number

2013-004324-11

A.3

Full title of the trial

Phase II study with oral fibroblast growth factor-1 inhibitor BIBF1120 as second line treatment in lung carcinoma patients harboring fibroblast growth factor receptor-1 gene amplification (NVALT-15 study)

A.3.1

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

Study with BIBF1120 in lung canger patients with an abnormal fibroblast growth factor-1 receptor (NVALT-15 study)

A.3.2

Name or abbreviated title of the trial where available

NVALT-15

A.4.1

Sponsor's protocol code number

NVALT-15

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	Stichting NVALT studies
B.1.3.4	Country	Netherlands
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	Stichting NVALT studies
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Stichting NVALT studies
B.5.2	Functional name of contact point	Principal investigator
B.5.3	Address:
B.5.3.1	Street Address	Luijbenstraat 15
B.5.3.2	Town/ city	dEN bOSCH
B.5.3.3	Post code	5211 BR
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	nananana
B.5.5	Fax number	nananana
B.5.6	E-mail	h.j.m.groen@umcg.nl

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.3.2	Product code	BIBF1120
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	No
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	nintedanib
D.3.9.1	CAS number	656247-17-5
D.3.9.2	Current sponsor code	BIBF1120
D.3.9.3	Other descriptive name	NINTEDANIB
D.3.9.4	EV Substance Code	SUB120728
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	200
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

Non small cell lung cancer

E.1.1.1

Medical condition in easily understood language

Lung cancer

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	20.0
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	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10029521
E.1.2	Term	Non-small cell lung cancer stage IIIB
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

Effect of BIBF1120 as a second line treatment on progression-free survival of patients with FGFR1 amplification.

E.2.2

Secondary objectives of the trial

Tumor response rate, duration of tumor response, overall survival, safety.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Stage IIIB or IV or recurrent NSCLC haboring a positive FISH for FGFR1 amplification (> 2 copies). Six unstained slides will be provided to the UMC Groningen to perform the test.
2. Age above 18 years.
3. Measurable tumor lesions (RECIST 1.1)
4. Life expectancy of at least 3 months.
5. Eastern Cooperative Oncology Group (ECOG) score of 0 - 1.
6. Patients who have sufficient baseline organ function and who meet the following criteria at the enrolment:
o Absolute neutrophil count (ANC) ≥ 1500/mm3;
o Platelet count ≥ 100 000/mm3;
o Total bilirubin under the upper limit of normal (=upper limit of the local laboratory facility);
o AST/SGOT and/or ALT/GPT <=1.5 x upper limit of normal (if related to liver metastases <=2.5 x upper limit of normal);
o Proteinuria Common Terminology Criteria for Adverse Events (CTCAE version 3.0) grade 1 or less;
o Calculated creatinine clearance by Cockcroft Gault ≥ 45 mL/min;
o Prothrombin time-international normalized ratio (PT-INR) and/or partial thromboplastin time (PTT) within normal limits;
o Oxygen saturation by pulse-oximeter SpO2 ≥ 92%;
7. Patient has given written informed consent which must be consistent with ICH-GCP and local legislation.

E.4

Principal exclusion criteria

1. Patients who have received treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial or who have not recovered from side effects of such therapy (except for alopecia).
2. Patients who have received chemo-, hormone-, immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug or who have not recovered from side effects of such therapy (except for alopecia).
3. Patients who have received radiotherapy on the target lesions within 4 weeks prior to treatment with the trial drug (in case of palliative radiotherapy such as for extremities, within 2 weeks prior to treatment with the trial drug).
4. Previous therapy with other vascular endothelial growth factor receptor (VEGFR) inhibitors or vascular endothelial growth factor (VEGF) ligand inhibitors for treatment of NSCLC.
5. Previous therapy with BIBF1120.
6. Patients who have symptomatic brain metastases or leptomeningeal disease.
7. Radiographic evidence of cavitation or necrotic tumors.
8. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels.
9. History of clinically significant haemoptysis within the past 3 months.
10. Known inherited predisposition to bleeding or thrombosis.
11. Current peripheral neuropathy CTCAE version 3.0 grade 2 or greater except due to trauma.
12. Pre-existing ascites and/or clinically significant pleural effusion.
13. Major injuries and/or surgery within the past 4 weeks prior to treatment.
14. Clinically serious infections.
15. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug.
16. Patients who have active or chronic hepatitis C and/or B infection and diagnosis of human immunodeficiency virus (HIV) infection.
17. Other malignancy other than basal cell skin cancer, carcinoma in situ or intra-mucosal cancer that were judged to be cured by adequate treatment and disease-free interval is more than 5 years.
18. History of serious drug hypersensitivity.
19. Serious illness or concomitant non-oncological disease such as neurologic-, psychiatric-, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation.
20. Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except acetylsalicylic acid up to 100 mg daily).
21. Patients who are sexually active and unwilling to use a medically acceptable method of contraception.
22. Pregnancy or breast feeding.
23. Patients unable to comply with the protocol.

E.5 End points

E.5.1

Primary end point(s)

Progression free survival

E.5.1.1

Timepoint(s) of evaluation of this end point

Continuously

E.5.2

Secondary end point(s)

Response, overall survival, safety

E.5.2.1

Timepoint(s) of evaluation of this end point

Continuously

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

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

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.8.3

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

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

Last patient last visit

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.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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 treatment

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

2014-03-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-06-02

P. End of Trial
P.	End of Trial Status	Ongoing

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