Clinical Trials Register

Summary
EudraCT Number:	2012-001877-94
Sponsor's Protocol Code Number:	COX-2I
National Competent Authority:	Slovenia - JAZMP
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-17
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

Slovenia - JAZMP

A.2

EudraCT number

2012-001877-94

A.3

Full title of the trial

Significance of COX-2 inhibition in first line treatment of extensive disease small-cell lung cancer (ED-SCLC)

POMEN COX-2 INHIBICIJE V PRVI LINIJI ZDRAVLJENJA RAZŠIRJENEGA DROBNOCELIČNEGA RAKA PLJUČ COX-2

A.3.1

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

Significance of COX-2 inhibition in first line treatment of extensive disease small-cell lung cancer (ED-SCLC)

POMEN COX-2 INHIBICIJE V PRVI LINIJI ZDRAVLJENJA RAZŠIRJENEGA DROBNOCELIČNEGA RAKA PLJUČ COX-2

A.3.2

Name or abbreviated title of the trial where available

COX-2I trial

COX-2I

A.4.1

Sponsor's protocol code number

COX-2I

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	UNIVERSITY CLINIC GOLNIK
B.1.3.4	Country	Slovenia
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	UNIVERSITY CLINIC GOLNIK
B.4.2	Country	Slovenia
B.4.1	Name of organisation providing support	PFIZER SARL podružnica slovenija
B.4.2	Country	Slovenia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	UNIVERSITY CLINIC GOLNIK
B.5.2	Functional name of contact point	RAZISKOVALNI ODDELEK
B.5.3	Address:
B.5.3.1	Street Address	GOLNIK 36
B.5.3.2	Town/ city	GOLNIK
B.5.3.3	Post code	4204 GOLNIK
B.5.3.4	Country	Slovenia
B.5.4	Telephone number	0038642569500
B.5.6	E-mail	jana.bogataj@klinika-golnik.si

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	Yes
D.2.1.1.1	Trade name	Celebrex
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Luxemburg SARL
D.2.1.2	Country which granted the Marketing Authorisation	Slovenia
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	NA
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Capsule, hard
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	celekoxib
D.3.9.1	CAS number	169590-42-5
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
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	800
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

extensive disease small-cell lung cancer (ED-SCLC)

razširjen drobnocelični rak pljuč

E.1.1.1

Medical condition in easily understood language

extensive disease small-cell lung cancer

razširjen drobnocelični rak pljuč

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Investigate the efficacy of combination of celecoxib and standard chemotherapy as first line treatment for ED-SCLC

Preučiti učinkovitost celekoksiba v kombinaciji s standardno kemoterapijo v prvi liniji zdravljenja razširjenega drobnoceličnega raka pljuč

E.2.2

Secondary objectives of the trial

•Validate the use of the progression free survival rate (PFSR) at 20 weeks as primary endpoint for the design of SCLC phase II trials
•Perform an explorative translational research program, looking at the use of serum CRP, tissue COX-2 expression, urinary PGE-M in the assessment of response and survival

•Ocena uporabe deleža preživetja brez bolezni pri 20 tednih (PFSR-20, progression-free survival rate) kot možen primarni cilj kliničnih raziskav faze 2 drobnoceličnega pljučnega
•Translacijska raziskava: ocena prognostične in prediktivne vrednosti biomarkerjev (tkivna ekspresija COX-2 proteina, serumskega CRP in PGE-M v urinu)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The study population will consist of patients aged 18 years and older with chemonaive, cytologicaly/histologicaly proven ED-SCLC.

Bolniki, vključeni v raziskavo bodo stari najmanj 18 let, s histološko ali citološko potrjenim razširjenim drobnoceličnim pljučnim rakom brez predhodnegas+ citostatskega zdravljenja.

E.4

Principal exclusion criteria

•Patients not understanding the disease and no signed written informed consent
•Life expectancy less than 12 weeks
•Other malignant disease except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin, or less than 3 years after treatment of other malignant disease
•Known hypersensitivity to acetylsalicylic acid, selective COX-2 inhibitors, other NSAIDs, or sulfonamides
•active ulcer disease
•ECOG PS more than 2
•One or more of the following cardiovascular conditions within the past 6 months:
- Myocardial infarction
- Cerebrovascular accident or transient ischemic attack
- Pulmonary embolism
- Unstable angina
- Symptomatic congestive heart failure or congestive heart failure NYHA III-IV
- Uncontrolled cardiac arrhythmia
- Uncontrolled hypertension
- Symptomatic carotid artery or peripheral vascular disease
- Deep vein thrombosis
- Other significant thromboembolic events
•Abnormal organ as defined below:
-severe hepatic dysfunction (AST/ALT> 5 x ULN, bilirubin > 4xUNL, serum albumine < g/L
-estimated creatinine clearance < 30 mL/min
•Other contraindication for PE/CEV/CAV treatment
•Pregnancy or breastfeeding
•Concomitant fluconazol treatment
•Galactose intolerance

•bolniki, ki ne razumjo bolezni oziroma ne podpišejo ozaveščenega pristanka
•pričakovana življenska doba manj kot 12 tednov
•Drugea sočasna maligna obolenja razen karcinom in situ materničnega vratuali bazalnocelični karcinom kože, ali manj kot 3 leta od zdravljenja zaradi drugega malignoma
•Znana preobčutljivost za acetilsalicilno kislino, selektivne COX-2 inhibitorje, druge NSAID in sulfonamide
•Aktivno ulkusno obolenje
•ECOG PS več kot 2
•Eden ali več spodaj naštetih zapletov znotraj 6 mesecev od pričetka zdravljenja:
- srčni infarkt
- cerebrovaskularni dogodek ali TIA
- pljučna embolija
- nestabilna angina pektoris
- simptomatsko srčno popuščanje (NYHA III-IV)
-neurejana motnja srčnega ritma
-neurejena arterijska hipertenzija
- simptomatska lezija karotid ali periferna okluzivna arterijska bolezen
- globoka venska tromboza
- drugi trombembiolični zapleti
•Nenormalna funkcija organov ocenjena kot::
-huda jetrna okvara (AST/ALT> 5 x ULN, bilirubin > 4xUNL, serumski albumin < g/L
-Očistek kreatinina < 30 mL/min
•Kontraindikacije za zdravljenje s kemoterapevtskimi shemami PE/CEV/CAV
•Nosečnost/dojenje
•zdravljenje s flukonazolom
•Galaktoznaa intoleranca

E.5 End points

E.5.1

Primary end point(s)

progression-free survival (PFS)

preživetje brez napredovanja bolezni

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

•Overall response rate (ORR)
•Progression free survival rate at 20 weeks (PFSR-20)
•Overall survival (OS)
•Safety and tolerability of celecoxib in combination with standard chemotherapy according to CTCAE version 4.0.
•COX-2 protein expression (IHC) and gene copy number (PCR) in primary tumor, CRP determination in serum and urinary PGE-M for the assessment of response rate and survival.

•PFSR-20: delež preživetja brez napredovanja bolezni pri 20 tednih
•OS: celokupno preživetje
•ORR: odgovor na zdravljenje
•Varnost in sopojavi zdravljenja: pogostnost in resnost sopojavov zdravljenja v skladu z NCI CTC, verzija 4.0
•Uporaba proteinske ekspresije COX-2 (IHC) pomnožitve (PCR) v primarnem tumorju, določanja CRP v serumu in PGE-M v urinu in za oceno odgovora na zdravljenje in preživetja

E.5.2.1

Timepoint(s) of evaluation of this end point

Patient will have a CT scan to define response/progression according to modified RECIST criteria after 6-9 weeks of chemotherapy treatment, at the end of chemotherapy treatment and every 2 months during celecoxib maintenance.
Treatment side effects will be assessed separately at every control visit.
COX-2 expression will be determined prior treatment initiation, CRP will be determined at every visit and PGE-M will be determined at the begining of the treatment, after 1.cycle of chemotherapy and at the time of progression.

Ocena učinka zdravljenja/progresa bolezni bo potekala v skladu po veljavnih RECIST kriterijih s CT preiskavami 6-9 tednov po pričetku zdravljenja, ob zaključku zdravljenja s kemoterapijo ter na 2 meseca tekom vzdrževalne terapije.
Neželeni učinski zdravljenja bodo ocenjevani ob vsakem obisku.
COX-2 proteinska ekspresija bo določena pred pričetkom zdravljenja, vrednost CRP ob vsakem obisku in PGE-M v urinu ob pričetku zdravljenja, po prvem ciklusu kemotreapije in ob progresu bolezni.

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

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.8.2.4

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

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

LVLS

Zadnji obisk zadnjega preiskovanca

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

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

F.3.3.1

Women of childbearing potential not using contraception