Clinical Trials Register

Summary
EudraCT Number:	2013-001630-18
Sponsor's Protocol Code Number:	INOX-EGJ
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-06-20
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2013-001630-18

A.3

Full title of the trial

Multicentre phase 2 study of neoadjuvant oxaliplatin and capecitabine followed by chemo-radiotherapy in patients with locally advanced carcinoma of esphago-gastric junction.

Studio multicentrico di fase II, di chemioterapia di induzione con Oxaliplatino e Capecitabina seguito da chemio-radioterapia con intento neoadiuvante in pazienti affetti da carcinoma della giunzione esofago-gastrica localmente avanzato.

A.3.1

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

Multicentre phase 2 study of neoadjuvant oxaliplatin and capecitabine followed by chemo-radiotherapy in patients with locally advanced carcinoma of esphago-gastric junction.

A.3.2

Name or abbreviated title of the trial where available

INduction Oxaliplatin and Xeloda in Esophago-Gastric Junction cancer

A.4.1

Sponsor's protocol code number

INOX-EGJ

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	Istituto Nazionale per lo Studio e la Cura dei Tumori di Napoli – Fondazione “G.Pascale”
B.1.3.4	Country	Italy
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	none
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Istituto Nazionale per lo Studio e la Cura dei Tumori di Napoli – Fondazione “G.Pascale”
B.5.2	Functional name of contact point	Clinical Trials Unit
B.5.3	Address:
B.5.3.1	Street Address	via M. Semmola
B.5.3.2	Town/ city	Napoli
B.5.3.3	Post code	80131
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390815903571
B.5.5	Fax number	+390817702938
B.5.6	E-mail	marilina.piccirillo@usc-intnapoli.net

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.2.1.2	Country which granted the Marketing Authorisation	Italy
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	oxaliplatin
D.3.4	Pharmaceutical form	Powder for 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	OXALIPLATIN
D.3.9.1	CAS number	61825-94-3
D.3.9.4	EV Substance Code	SUB09490MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	130
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.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	Yes
D.2.1.1.1	Trade name	Xeloda
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	capecitabine
D.3.4	Pharmaceutical form	Film-coated 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	capecitabine
D.3.9.3	Other descriptive name	CAPECITABINE
D.3.9.4	EV Substance Code	SUB12474MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2000
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

Locally advanced carcinoma (squamous or adenocarcinoma) of the esophago-gastric junction Siewert type I and II

Carcinoma (adenocarcinoma o carcinoma squamoso) della giunzione esofago-gastrica tipo I e II secondo Siewert localmente avanzato

E.1.1.1

Medical condition in easily understood language

Locally advanced esophago-gastric junction carcinoma

Carcinoma della giunzione esofago-gastrica localmente avanzato

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	10056267
E.1.2	Term	Gastroesophageal cancer
E.1.2	System Organ Class	100000004864

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 the activity in terms of pathological complete response rate (pCR) of a neoadjuvant treatment with XELOX followed by chemo-RT in patients with locally advanced (stage IB-III) carcinoma of the esophagogastric junction .

Valutare l’attività in termini di percentuale di risposte complete patologiche (pCR) di un trattamento ad intento neoadiuvante con XELOX seguito da chemio-RT in pazienti affetti da carcinoma della giunzione esofago-gastrica localmente avanzato (stadio IB-III).

E.2.2

Secondary objectives of the trial

• To evaluate:
objective response rate
toxicity
rate of R0 resections
progression-free survival (PFS)
overall survival (OS)

• To validate the predictive role of early metabolic changes of the tumor measured by PET / CT
• To evaluate the prognostic role of the immunocompetent cell subsets CD4, CD8, CD20, CD57, CD68

• Valutare:
o tasso di risposte obiettive
o tossicità
o tasso di resezioni R0
o sopravvivenza libera da progressione (PFS)
o sopravvivenza globale (OS)

• Validare il ruolo predittivo dei cambiamenti metabolici precoci a carico della neoplasia misurati con esame PET/TC
• Valutare il ruolo prognostico di sottopopolazioni cellulari immunocompetenti CD4, CD8, CD20, CD57, CD68

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Carcinoma of the esophagogastric junction Siewert type I and II locally advanced (T2-3-4, N +) documented by histology and / or cytology
 Age ≥ 18 and ≤ 75 years
 Presence of at least one target lesion according to RECIST
 Performance Status ECOG = 0-1
 Adequate bone marrow , hepatic and renal function
 Estimated life expectancy> 3 months
 Written informed consent

 Carcinoma of the esophagogastric junction Siewert type I and II sec locally advanced (T2-3-4, N +) documented by histology and / or cytology
 Age ≥ 18 years and ≤ 75 years
 Presence of measurable target lesions according to RECIST
 Performance Status ECOG = 0-1
 Lack of significant changes in bone marrow function, hepatic and renal
 estimated life expectancy> 3 months
 Written informed consent

 Carcinoma della giunzione esofago-gastrica tipo I e II sec Siewert localmente avanzato (T2-3-4, N+) documentato mediante esame istologico e/o citologico
 Età ≥ 18 anni e ≤ 75 anni
 Presenza di lesioni target misurabili secondo i criteri RECIST
 Performance Status secondo ECOG = 0-1
 Assenza di rilevanti alterazioni della funzionalità midollare, epatica e renale
 Aspettativa di vita stimata > 3 mesi
 Consenso informato scritto

E.4

Principal exclusion criteria

 Distant metastases
 Previous systemic medical treatment or radiotherapy for neoplastic disease
 Presence of concomitant and / or previous malignancies
 Presence of acute or chronic infectious states requiring systemic medical therapies.
 Significant cardiovascular disease (myocardial infarction, unstable angina, congestive heart failure, arrhythmias) occurred less than 18 months prior to the enrollment
 Cerebro-vascular disorders
 Venous or arterial thromboembolism in place
 Severe respiratory diseases
 Inflammatory Bowel diseases
 Known Seropositivity for HIV
 Acute or chronic HBV or HCV hepatitis
 Peripheral neuropathy of any etiology
 Hepatic or renal impairment
 Any other clinically significant systemic disease that can make the patient unsuitable for study treatment
- Major surgery less than 28 days, or minor surgical procedure practiced less than 14 days before the start of treatment (excluding the placement of CVC)
 Pregnant or breastfeeding
 Dementia or other significant condition of altered mental status that may affect the ability of understanding of the scope of the study by the patient and the proper granting of informed consent

 Metastasi a distanza
 Precedente trattamento medico sistemico o radioterapico per la malattia neoplastica
 Presenza di concomitanti e/o pregresse neoplasie maligne
 Presenza di stati infettivi acuti o cronici richiedenti terapie mediche sistemiche.
 Significative patologie cardiovascolari (infarto del miocardio, angina instabile, scompenso cardiaco congestizio, aritmie) occorse meno di 18 mesi prima dell’eventuale arruolamento
 Patologie cerebro-vascolari
 Tromboembolie venose o arteriose in atto
 Gravi patologie respiratorie
 Malattie infiammatorie croniche intestinali
 Sieropositività conosciuta per HIV
 Epatite acuta o cronica da HBV o HCV
 Neuropatia periferica di qualsiasi eziologia
 Insufficienza epatica o renale
 Qualsiasi altra patologia sistemica clinicamente rilevante che si ritenga possa rendere il paziente inidoneo al trattamento in studio
 Intervento di chirurgia maggiore effettuato meno di 28 giorni oppure procedura chirurgica minore praticata meno di 14 giorni prima dell’inizio del trattamento (escluso il posizionamento di CVC)
 Stato di gravidanza o allattamento
 Demenza o altra significativa condizione di alterazione dello stato mentale che possa inficiare la capacità di comprensione degli scopi dello studio da parte del paziente e la corretta concessione del consenso informato da parte dello stesso

E.5 End points

E.5.1

Primary end point(s)

rate of complete pathologic response

tasso di risposte patologiche complete

E.5.1.1

Timepoint(s) of evaluation of this end point

surgery (about 21 weeks from study start)

intervento chirurgico (circa 21 settimane dalla randomizzazione)

E.5.2

Secondary end point(s)

objective response rate
toxicity
R0 resection rate
PFS
OS

tasso di risposte obiettive; tossicità; tasso di resezioni R0; sopravvivenza libera da progressione (PFS); sopravvivenza globale (OS).

E.5.2.1

Timepoint(s) of evaluation of this end point

objective response rate: week 20
toxicity: every week
R0 resection rate: surgery (about week 21)
PFS: week 20 and every 3 months later
OS. death

tasso di risposte obiettive: settimana 20
tossicità: ogni settimana
tasso di resezioni R0: intervento chirurgico (circa 21 settimane dopo la randomizzazione)
sopravvivenza libera da progressione: settimana 20 e successivamente ogni 3 mesi
sopravvivenza globale: decesso

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

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

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

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.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)

not different from clinical practice for this condition

non diverso dalla pratica clinica per la specifica condizione

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

2013-07-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-26

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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