Clinical Trials Register

Summary
EudraCT Number:	2009-016509-41
Sponsor's Protocol Code Number:	BR.26
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:	2011-12-27
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

2009-016509-41

A.3

Full title of the trial

A double-blind placebo controlled randomized trial of PF-804 in patients with incurable stage IIIB/IV non-small cell lung cancer after failure of standard therapy for advanced or metastatic disease.

Studio doppio-cieco, controllato vs placebo, randomizzato, su PF-804 in pazienti con cancro del polmone non a piccole cellule incurabile stadio IIIB/IV, dopo fallimento della terapia standard per la malattia avanzata o metastatica.

A.4.1

Sponsor's protocol code number

BR.26

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	WWCR, WORLDWIDE CLINICAL RESEARCH
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	WWCR Worldwide Clinical Research
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	Dimensione Ricerca
B.5.2	Functional name of contact point	Direttore Generale
B.5.3	Address:
B.5.3.1	Street Address	Viale Parioli 12
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00197
B.5.3.4	Country	Italy
B.5.4	Telephone number	0039 06 8076072
B.5.5	Fax number	0039 06 80693521
B.5.6	E-mail	s.marini@dimensione-ricerca.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	4-piperidin-1yl-but-2enoic acid[4-(3-chloro-4fluoro-phenylamino)-7-methoxyquinazol-6-yl]-amin monhyd
D.3.2	Product code	PF-00299804
D.3.4	Pharmaceutical form	Tablet
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	OTHER ANTINEOPLASTIC AGENTS
D.3.9.1	CAS number	1042385-75-0
D.3.9.2	Current sponsor code	PF-804
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	15
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
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

Incurable stage IIIB/IV non-small cell lung cancer after failure of standard therapy for advanced or metastatic disease.

Carcinoma polmonare non a piccole cellule stadio IIIB/IV incurabile dopo fallimento della terapia standard per la malattia avanzata o metastatica.

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10025054
E.1.2	Term	Lung cancer non-small cell stage IIIB
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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10025055
E.1.2	Term	Lung cancer non-small cell stage IV
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 compare overall survival (OS) between the 2 arms

Confrontare la sopravvivenza complessiva (Overall Survival, OS) nei due gruppi

E.2.2

Secondary objectives of the trial

To compare overall survival (OS) in KRAS-WT patients between the 2 arms; To compare overall survival (OS) in EGFR mutant patients between the 2 arms; To compare progression-free survival (PFS) between arms; To compare objective response rates (RR) between arms; To estimate time to response and response duration; To evaluate the nature, severity, and frequency of toxicities, between arms; To compare Quality of Life between the 2 arms; To determine the incremental cost effectiveness and cost utility ratios for PF-804; To correlate the expression of tissue and blood markers (at diagnosis) with outcomes and response.

Confrontare la sopravvivenza globale (OS) tra i due gruppi nei pazienti KRAS-WT; Confrontare la sopravvivenza globale (OS) tra i due gruppi nei pazienti con mutazioni EGFR; Confrontare la sopravvivenza libera da progressione (PSF) tra i due gruppi; Confrontare la % di risposte obiettive (RR) tra i due gruppi; Stimare il tempo alla risposta e la durata della risposta; Valutare la natura, la gravita' e la frequenza di tossicita' tra i due gruppi; Confrontare la qualita' della vita tra i due gruppi; Determinare i rapporti costo-efficacia e costo-utilita' di PF-804; Correlare l'espressione dei markers tissutali ed ematici (alla diagnosi) con gli esiti e la risposta.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Histologically confirmed diagnosis of non-small cell carcinoma of the lung; Patients must have evidence of disease, but measurable disease is not mandatory. (to be considered evaluable for complete or partial response assessment, patients must have at least one measurable lesion as follows: X-ray >or= 20 mm Spiral CT scan or physical exam >or= 10 mm; Male or female, 18 years of age or older; ECOG performance status of 0, 1, 2 or 3 (patients with performance status of 3 are eligible providing that the investigator attests that the patient has a reasonable life expectancy (>or= 6 weeks); Adequate renal (Creatinine <1.5 upper limit of normal) and hepatic (total bilirubin < 1.5 upper limit of normal; ALT (SGPT) < 2.5 times the upper limit of normal. Note: If clearly attributable to liver metastasis, ALT (SGPT) values < 5 times the upper limit of normal are permitted) within 14 days prior to randomization. (if anemic, patients should be asymptomatic and should not be decompensated); Previous Therapy (see § 5.1.6 of the protocol study); Patient able and willing to complete the quality of life questionnaires; Written patient consent; Patients availability for treatment and follow-up; treatment begins within 2 working day of patient randomization.

Diagnosi confermata istologicamente di carcinoma polmonare non a piccole cellule; Evidenza di malattia, ma non e' indispensabile disporre di un parametro di misurazione quantitativa (per essere considerati valutabili per la valutazione della risposta completa o parziale, i pazienti devono avere almeno una lesione misurabile come segue: raggi-X maggiore o uguale a 20 mm, TC spirale o esame fisico maggiore o uguale a 10 mm); Maschi o Femmine di eta' maggiore o uguale a 18 anni; ECOG (stato di performance): 0,1,2 o 3 (stato 3: solo se lo sperimentatore attesta che l'aspettativa di vita e' maggiore o uguale a 6 settimane); Adeguati valori di funzionalita' renale (creatinina < 1,5 il limite superiore del V.N.) ed epatica (bilirubina totale < 1,5 il limite superiore del V.N.; ALT (SGPT) < 2,5 volte il limite superiore V.N. nei pazienti senza metastasi epatiche e < 5 volte il limite superiore V.N. nei pazienti con metastasi epatiche), nei 14 giorni precedenti la randomizzazione (se anemici, i pazienti dovrebbero essere asintomatici e non scompensati); Pregressa terapia (vedere § 5.1.6 del protocollo); Capacita' e volonta' di completare i questionari per la valutare la QoL; Consenso informato scritto; Reperibilita' del paziente per il trattamento e per il follow-up; Inizio del trattamento entro 2 giorni lavorativi dalla randomizzazione.

E.4

Principal exclusion criteria

Patients receiving concurrent treatment with other experimental drugs or anti-cancer therapy; Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if controlled, should have a LVEF > 50%; Patients with untreated brain or meningeal metastases or treated with corticosteroids at least 1 week prior to randomization; Patients with active or uncontrolled infections, or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol, including: severe dry eye syndrome, keratoconjunctivitis sicca, Sjogren s syndrome, severe exposure keratopathy, disorders that might increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis), uncontrolled inflammatory gastrointestinal diseases (Crohn's, ulcerative colitis etc), prior pneumonitis/ILD secondary to EGFR inhibitors, mean QTc > 470 msec or history of familial long QT syndrome, drugs that are highly dependent on CYP2D6 for metabolism (see § 5.2.6 of the protocol study), pregnancy or inadequate contraception.

Trattamento concomitante con altri farmaci sperimentali o con terapie antitumorali; Condizioni cardiovascolari non trattate e/o non controllate e/o disfunzione cardiache sintomatiche (angina instabile, insufficienza cardiaca congestizia, infarto miocardico nel precedente anno o aritmie ventricolari cardiache che richiedono trattamento, anamnesi di alterazioni della conduzione atrio-ventricolare di 2° o 3° grado). I pazienti con anamnesi cardiaca significativa, anche se controllati, dovrebbero avere una LVEF > 50%; Pazienti con metastasi cerebrali o meningee non trattate o trattate con corticosteroidi non oltre la settimana precedente la randomizzazione; Pazienti con infezioni attive o non controllate o con malattie gravi o condizioni mediche che non permetterebbero al paziente di essere seguito secondo il protocollo, comprendenti: sindrome grave dell'occhio secco, cheratocongiuntivite secca, sindrome di Sjogren, cheratopatia grave, alterazioni che potrebbero aumentare il rischio di complicazioni epiteliali (es. cheratopatia bollosa, aniridi, ustioni chimiche gravi, cheratiti neutrofile), malattie gastrointestinali non controllate (es. malattia di Crohn, colite ulcerosa, ecc), pregressa polmonite/malattia interstiziale polmonare secondaria a inibitori del EGFR, QTc medio > 470 msec o anamnesi familiare di sindrome del tratto QT lungo, trattamento con farmaci metabolizzati dal CYP2D6 (vedere § 5.2.6 del protocollo), gravidanza o inadeguata contraccezione.

E.5 End points

E.5.1

Primary end point(s)

To compare overall survival (OS) between the 2 arms.

Confrontare la sopravvivenza globale (OS) nei 2 gruppi.

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

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

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

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

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	No
F.1.1	Number of subjects for this age range:	0
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	No
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	50
F.4.2	For a multinational trial
F.4.2.1	In the EEA	50
F.4.2.2	In the whole clinical trial	720

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	NCIC CTG

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2010-07-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-06-23

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

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