Clinical Trials Register

Summary
EudraCT Number:	2014-003443-35
Sponsor's Protocol Code Number:	AV-299-14-206
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:	2014-12-02
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

2014-003443-35

A.3

Full title of the trial

A Phase 2, multicenter, randomized, double-blind study of ficlatuzumab plus erlotinib versus placebo plus erlotinib in subjects who have previously untreated metastatic, EGFR-mutated non-small cell lung cancer (NSCLC) and BDX004 Positive Label

A.3.1

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

A study of ficlatuzumab in subjects with metastatic lung cancer who will receive erlotinib

A.4.1

Sponsor's protocol code number

AV-299-14-206

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	AVEO Pharmaceuticals
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	AVEO Pharmaceuticals
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	PAREXEL Informatics
B.5.2	Functional name of contact point	Customer Care Services
B.5.3	Address:
B.5.3.1	Street Address	Lady Bay House, Meadow Grove
B.5.3.2	Town/ city	Nottingham
B.5.3.3	Post code	NG2 3HF
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	0800 3890918
B.5.5	Fax number	0800 389 3669
B.5.6	E-mail	customercare@perceptive.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	Ficlatuzumab
D.3.2	Product code	AV-299
D.3.4	Pharmaceutical form	Concentrate for solution for injection/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	Ficlatuzumab
D.3.9.1	CAS number	1174900-84-5
D.3.9.2	Current sponsor code	AV-299
D.3.9.3	Other descriptive name	formerly known as SCH 900105
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	50
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.8.3	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

EGFR-mutated non-small cell lung cancer (NSCLC)

E.1.1.1

Medical condition in easily understood language

Non-small cell lung cancer (NSCLC)

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 the efficacy of ficlatuzumab plus erlotinib versus placebo plus erlotinib in terms of PFS in subjects who have previously untreated metastatic EGFR-mutated NSCLC and a BDX004 Positive Label.

E.2.2

Secondary objectives of the trial

• To evaluate OS in the 2 treatment groups.
• To compare ORR in the 2 treatment groups.
• To evaluate disease control rate (DCR) in the 2 treatment groups.
• To evaluate safety and tolerability of ficlatuzumab plus erlotinib versus placebo plus erlotinib in subjects who have previously untreated metastatic EGFR-mutated NSCLC and a BDX004 Positive Label.
• To evaluate the pharmacokinetics of ficlatuzumab and erlotinib.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female and ≥18 years of age.
2. Histologically and/or cytologically confirmed primary diagnosis of Stage IV NSCLC (according to American Joint Committee on Cancer [AJCC] 7th edition lung cancer staging criteria).
3. Measurable disease according to RECIST v.1.1.
4. An EGFR exon 19 deletion and/or an exon 21 (L858R) substitution mutation.
5. BDX004 Positive Label.
6. Have received no prior systemic chemotherapy, immunotherapy, targeted therapy, or biologic therapy for metastatic NSCLC. Subjects may have previously been treated with postoperative adjuvant chemotherapy for early stage lung cancer or chemo-radiotherapy for locally advanced disease provided this was completed at least 6 months prior to enrollment. No prior EGFR TKI therapy is allowed for any stage of NSCLC.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Clinical laboratory values meeting the following criteria prior to randomization:
• Serum creatinine ≤1.5 x upper limit of normal (ULN).
• Total bilirubin ≤1.5 x ULN.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN, or AST and ALT ≤5 x ULN if liver metastases.
• Activated partial thromboplastin time (aPTT) ≤1.5 x ULN and prothrombin time/international normalized ratio (PT/INR) ≤1.5 x ULN if not on anticoagulation therapy. Subjects receiving anti-coagulation therapy with an agent such as warfarin or low-molecular weight heparin may be allowed to participate if the subject is on a stable dose of anticoagulant and coagulation test results are in the therapeutic range established prior to initiation of study treatment.
• Hematologic function:
- Absolute neutrophil count (ANC) ≥1,500 cells/μL.
- Hemoglobin ≥9 g/dL or 5.6 mmol/L.
- Platelet count ≥100,000/μL.
9. For female subjects of childbearing potential, documentation of negative serum pregnancy test prior to randomization.
10. For female subjects of childbearing potential and male subjects whose sexual partners are of childbearing potential, agreement to use an effective method of contraception during the study and for at least 30 days after the last dose of study treatment. Effective birth control includes (a) intrauterine device plus one barrier method; (b) oral, implantable or injectable contraceptive plus one barrier method; or (c) two barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).
11. Ability to give written informed consent and comply with protocol requirements

E.4

Principal exclusion criteria

1. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent or erlotinib.
2. History of known brain metastases.
3. Prior treatment with any other investigational drug or biologic agent within 5 half-lives prior to randomization, or any investigational device within 2 weeks prior to randomization.
4. Any unresolved toxicity from previous radiation therapy.
5. Significant cardiovascular disease, including:
• Echocardiogram (ECHO) or multiple gated acquisition (MUGA) showing left ventricular ejection fraction of less than 55%.
• Cardiac failure New York Heart Association class III or IV.
• Myocardial infarction, severe or unstable angina within 6 months prior to randomization.
• History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation).
• Significant thrombotic or embolic events within 3 months prior to randomization (significant thrombotic or embolic events include but are not limited to stroke or transient ischemic attack). Catheter-related thrombosis is not a cause for exclusion. Diagnosis of deep vein thrombosis or pulmonary embolism is allowed if it occurred >3 months prior to randomization.
• Any uncontrolled or severe cardiovascular disease.
6. Any other medical condition (eg, alcohol abuse) or psychiatric condition that, in the opinion of the Investigator, might interfere with the subject’s participation in the trial or interfere with the interpretation of trial results.
7. History of prior malignancy within 3 years prior to randomization (except for adequately treated non-melanoma skin cancer, carcinoma in situ of the breast or cervix, superficial bladder cancer, or early stage prostate cancer, without evidence of recurrence).
8. Major surgery within 4 weeks prior to randomization.
9. Serious and/or symptomatic active infection within 14 days prior to first dose of study drug. Subjects who have asymptomatic or mild infection and are currently taking a short course of antibiotics (eg, urinary tract infection, bronchitis) may be allowed after discussion with the Medical Monitor.
10. Known human immunodeficiency virus infection.
11. Radiographic evidence of interstitial lung disease.
12. For female subjects, pregnancy or breast feeding.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint PFS is defined as the time from the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause.

E.5.1.1

Timepoint(s) of evaluation of this end point

please refer to E.5

E.5.2

Secondary end point(s)

- overall survival (OS), as measured from the date of randomization to the date of death by any cause;
- objective response rate (ORR) based on subjects that had complete response (CR) or partial response (PR);
-disease control rate (DCR) based on subjects that had CR or PR or stable disease (SD) for at least 4 cycles (16 weeks)

E.5.2.1

Timepoint(s) of evaluation of this end point

please refer to E.5.2

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

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

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.8.2.4

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

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

Australia

Hong Kong

Italy

Korea, Republic of

Singapore

Taiwan

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

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.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)

Subjects will continue until progression. After the End of Treatment Visit patients must complete the Post-Treatment Safety Visit assessments in advance of starting the new anti-cancer therapy.

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

2015-03-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-07-16

P. End of Trial
P.	End of Trial Status	Completed

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