Clinical Trials Register

Summary
EudraCT Number:	2013-001096-20
Sponsor's Protocol Code Number:	1169/2013
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-01-31
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

2013-001096-20

A.3

Full title of the trial

ASSOCIATION BETWEEN PROTON-PUMP INHIBITORS (PPI) and METRONOMIC CAPECITABINE (mCAP) AS SALVAGE TREATMENT FOR PATIENTS WITH ADVANCED GASTRO-INTESTINAL TUMOURS: A RANDOMIZED PHASE II STUDY

Inibitori di pompa protonica in associazione a Capecitabina metronomica nei pazienti con neoplasie gastrointestinali non eleggibili per un trattamento chemioterapico convenzionale: studio di fase II randomizzato

A.3.1

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

Salvage chemotherapy with daily, low, continuously administered dose of capecitabine and proton-pump inhibitors in advanced gastro-intestinal
tumours

Terapia di salvataggio con basse dosi di Capecitabina, giornaliera, continuativa, associata ad inibitori di pompa protonica nei tumori
gastrointestinali avanzati

A.3.2

Name or abbreviated title of the trial where available

metroCAP+PPI

CAPmetro+PPI

A.4.1

Sponsor's protocol code number

1169/2013

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	Department of Molecular and Clinical Medicine; "Sapienza" University of Rome
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	Department of Molecular and Clinical Medicine; "Sapienza" University of Rome
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	Sant'Andrea Hospital
B.5.2	Functional name of contact point	Medical Oncology
B.5.3	Address:
B.5.3.1	Street Address	via di grottarossa 1035
B.5.3.2	Town/ city	rome
B.5.3.3	Post code	00189
B.5.3.4	Country	Italy
B.5.4	Telephone number	00390633775800

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	Pariet
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag Spa
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	Pariet
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	RABEPRAZOLE
D.3.9.1	CAS number	117976-89-3
D.3.9.2	Current sponsor code	1169/2013
D.3.9.4	EV Substance Code	SUB10229MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
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 Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Xeloda
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	capecitabine
D.3.9.1	CAS number	158798-73-3
D.3.9.2	Current sponsor code	1169/2013
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 milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1500
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

Patients with gastrointestinal malignancies ineligible for conventional chemotherapy

Pazienti con neoplasie gastrointestinali non eleggibili per un trattamento chemioterapico convenzionale

E.1.1.1

Medical condition in easily understood language

Patients with advanced tumors of the gastrointestinal tract

Pazienti con tumori del tratto gastroenterico avanzati

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

This is a single centre, open label, randomized fase II study to determine safety and activity of a combination of the PPI Rabeprazolo (1.5 mg/kg)
and mCAP (1500 mg/die) compared to mCAP.

Questo è uno studio di fase II monocentrico, aperto, randomizzato per determinare la sicurezza e l'attività di una combinazione del PPI Rabeprazolo (1,5 mg / kg)
e capecitabina metronomica (1500 mg / die) rispetto a MCAP.

E.2.2

Secondary objectives of the trial

To evaluate the clinical benefit rate (CBR), defined as the sum of complete responses (CR), partial responses (PR) and prolonged stabilization of disease (PSD), ie, lasting ≥ 24 weeks

valutare il tasso di Beneficio Clinico (CBR), definito come la somma delle risposte complete (CR), delle risposte parziali (PR) e delle stabilizzazioni di malattia prolungate (pSD), cioè di durata ≥ 24 settimane

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. pre-treated patients with advanced gastro-intestinal tumours 2. performance status (ECOG) ≤2
3. life espectancy > 3 months
4. adequate organ (liver, kidney, heart and bone marrow) function 5. patients must sign the consent form prior to registration
6. patients must be accessible for treatment and follow up

1. pazienti pre-trattati con tumori gastro-intestinali avanzate
2. performance status (ECOG) ≤ 2
3. aspettativa di vita> 3 mesi
4. adeguata funzionalità d'organo (fegato, rene, cuore e midollo osseo) funzione
5. i pazienti devono firmare il modulo di consenso prima della registrazione
6. i pazienti devono essere accessibili per il trattamento e il follow-up

E.4

Principal exclusion criteria

1. Gastrointestinal tumours that can be treated with standard treatments
2. Cardiovascular or CNS disease.
3. Previously untreated CNS metastases.
4. Pregnant or breast-feeding patients.
5. Organ dysfunctions that usually hinder the use of cytotoxic drugs 6. Substance abuse and any other condition which may interfere with patient's participation in the study or evaluation of study results

1. Tumori gastrointestinali che possono essere trattati con trattamenti standard
2. Malattie cardiovascolari o malattie del sistema nervoso centrale.
3. Metastasi al SNC precedentemente non trattati.
4. Gravidanza o allattamento pazienti.
5. Disfunzioni d'organo che di solito impediscono l'uso di farmaci citotossici
6. Abuso di sostanze e qualsiasi altra condizione che potrebbe interferire con la partecipazione del paziente allo studio o valutazione dei risultati dello studio

E.5 End points

E.5.1

Primary end point(s)

1. 3-months progression-free survival (PFS).PFS is defined as the interval from the first dose of study drug to the date of the first
documented disease progression or death for any reason, with censoring at the date of last contact for alive patients.
2. Safety (CTCAE v.4.03)

1. sopravvivenza libera da progressione (PFS) a 4 mesi. La PFS è definito come l'intervallo dalla prima dose del farmaco in studio alla data della prima
documentata progressione di malattia o morte per qualsiasi motivo, censurando i pazienti vivi alla data dell'ultimo controllo.
2. Sicurezza (CTCAE v.4.03)

E.5.1.1

Timepoint(s) of evaluation of this end point

4 months

4 mesi

E.5.2

Secondary end point(s)

evaluate the clinical benefit rate, overall survival (OS), the pharmacokinetics of capecitabine monotherapy and in combination with rabeprazole

valutare il tasso di Beneficio Clinico; la sopravvivenza globale (OS); la farmacocinetica della Capecitabina in monoterapia ed in combinazione con il Rabeprazolo

E.5.2.1

Timepoint(s) of evaluation of this end point

24 months

24 mesi

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

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

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

Yes

E.8.4

The trial involves multiple sites in the 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

fino all'ultima visita dell'ultimo paziente reclutato

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