Clinical Trials Register

Summary
EudraCT Number:	2010-024595-26
Sponsor's Protocol Code Number:	287-11-201
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:	2011-09-05
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

2010-024595-26

A.3

Full title of the trial

Phase 2 Placebo-controlled Double-Blind Trial of Dasatinib Added to Gemcitabine for Subjects with Locally-Advanced Pancreatic Cancer

Studio di fase 2, controllato con placebo, in doppio cieco, su dasatinib in combinazione con gemcitabina in soggetti affetti da cancro pancreatico localmente avanzato

A.3.1

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

Study for people with locvally advanced pancreatic cancer (inoperable but without distant spread) of gemcitabine chemiotherapy plus either dasatinib or placebo

Studio in pazienti con tumore pancreatico localmente avanzato (non operabile ma in assenza di metastasi)sulla combinazione della terapia con gemcitabina piu' dasatinib o placebo.

A.4.1

Sponsor's protocol code number

287-11-201

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	OTSUKA PHARMACEUTICAL DEVELOPMENT AND COMMERCIALISATION INC
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	OTSUKA PHARMACEUTICAL DEVELOPMENT AND COMMERCIALISATION INC
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	Covance CAPS
B.5.2	Functional name of contact point	Konstantin Stoitchkov
B.5.3	Address:
B.5.3.1	Street Address	Ave. Marcel Thiry 77
B.5.3.2	Town/ city	Brussels
B.5.3.3	Post code	1200
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+32 2 779 1870
B.5.5	Fax number	+32 2 779 1870
B.5.6	E-mail	konstantin.stoitchkov@covance.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	Yes
D.2.1.1.1	Trade name	SPRYCEL
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL-MYERS SQUIBB PHARMA EEIG
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.3.4	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.3.9.3	Other descriptive name	DASATINIB MONOHYDRATE
D.3.9.4	EV Substance Code	SUB23159
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	20
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	SPRYCEL
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL-MYERS SQUIBB PHARMA EEIG
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.3.4	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.3.9.3	Other descriptive name	DASATINIB MONOHYDRATE
D.3.9.4	EV Substance Code	SUB23159
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	50
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

Locally-advanced Pancreatic Adenocarcinoma

Adenocarcinoma Pancreatico Localmente Avanzato

E.1.1.1

Medical condition in easily understood language

Locally advanced pancreatic cancer (inoperable but without distant spread)

Tumore pancreatico localmente avanzato non operabile, ma in assenza di metastasi)

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	14.0
E.1.2	Level	HLT
E.1.2	Classification code	10033633
E.1.2	Term	Pancreatic neoplasms malignant (excl islet cell and carcinoid)
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) of
subjects with locally advanced pancreatic cancer (LAPC) who are
randomized to receive dasatinib added to standard of care (gemcitabine
[GEM]) versus standard of care (GEM) plus placebo

•Confrontare la sopravvivenza generale dei soggetti affetti da cancro pancreatico localmente avanzato randomizzati a ricevere il dasatinib in combinazione allo standard di cura (gemcitabina [GEM]) rispetto allo standard di cura (GEM) più placebo.

E.2.2

Secondary objectives of the trial

- To compare progression-free survival (PFS) in subjects receiving dasatinib added to standard of care (gemcitabine [GEM]) versus standard of care (GEM) plus placebo.
- To compare safety in subjects receiving dasatinib added to standard of care (GEM) versus standard of care (GEM) plus placebo.

- Confrontare la sopravvivenza senza progressione dei soggetti che ricevono il dasatinib in combinazione allo standard di cura (gemcitabina [GEM]) rispetto allo standard di cura (GEM) più placebo.
- Confrontare la sicurezza dei soggetti che ricevono il dasatinib in combinazione allo standard di cura (GEM) rispetto allo standard di cura (GEM) più placebo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female subjects ≥ 18 years of age.
2. Histologic or cytologic documentation of adenocarcinoma of the pancreas.
3. Unresectable disease due to local extension or invasion, for example:
 Tumor extension precluding resection, eg, mesenteric or retroperitoneal structures, vascular encasement, etc, or
 Lymph node involvement beyond the surgical field.
4. Recovery from toxicity of previous procedures that establishes diagnosis of locally advanced disease (patients with previous pancreatic resection are excluded)
5. ECOG PS 0 or 1
6. Adequate organ function:
− Absolute neutrophil count ≥ 1,500/µL
− Platelets ≥ 100,000/µL
− Bilirubin ≤ 2.0 X upper limit of normal (ULN)
− Creatinine ≤ 1.5 mg/dL
− Aspartate transaminase ≤ 2.5 X ULN

1. Pazienti di sesso maschile e femminile ≥ 18 anni d'età
2. Documentazione istologica o citologica di adenocarcinoma del pancreas.
3. Malattia non resecabile a causa di invasione o estensione locale, ad esempio:
Estensione del tumore che preclude la resezione, ad esempio strutture mesenteriche o retroperitoneali, encasement vascolare, ecc, o
Coinvolgimento dei linfonodi oltre il campo chirurgico.
4. Recupero dalla tossicità di procedure precedenti che definisce la diagnosi di malattia localmente avanzata (i pazienti con precedente resezione pancreatica sono esclusi)
5. ECOG PS 0 o 1
6. Funzione degli organi adeguata:
- Conta assoluta dei neutrofili ≥ 1.500/µL
− Piastrine ≥ 100.000/µL
− Bilirubina ≤ 2,0 volte il limite superiore dell’intervallo normale di riferimento (upper limit of normal - ULN)
− Creatinina ≤ 1,5 mg/dL
− Aspartato transaminasi ≤ 2,5 volte il limite superiore dell’intervallo normale di riferimento

E.4

Principal exclusion criteria

1.Evidence of metastatic disease based on symptoms, laboratory values, or imaging studies ≤ 21 days prior to the first dose of IMP
2.Previous radiotherapy or chemoradiotherapy
3.History of or current pleural effusion (any cause, ≥ Grade 1) within 6 months prior to the first dose of IMP. An equivocal finding at the costophrenic angle is allowed
4.History of significant cardiovascular disease or the following events within 6 months prior to the first dose of IMP: coronary infarction, life-threatening arrhythmia, or QTc prolongation > 470 ms
5.Clinically significant bleeding disorder or coagulopathy (eg, von Willebrand’s disease)
6.Requirement for a concomitant medication that is a strong inhibitor of Cytochrome P450 (CYP) 3A4

1.Evidenza di malattia metastatica in base a sintomi, valori di laboratorio o studi di diagnostica per immagini ≤ 21 giorni prima della dose iniziale del farmaco sperimentale
2.Radioterapia o chemioterapia precedente
3.Effusione pleurica pregressa o corrente (qualsiasi causa, ≥ grado 1) entro 6 mesi prima della dose iniziale del farmaco sperimentale. È consentito un risultato equivoco a livello dell'angolo costofrenico
4.Anamnesi di malattia cardiovascolare significativa o dei seguenti eventi entro 6 mesi prima della dose iniziale del farmaco sperimentale: infarto coronario, aritmia potenzialmente letale o QTc prolungato > 470 ms
5.Coagulopatia o disturbo emorragico clinicamente significativo (ad esempio, malattia di von Willebrand)
6.Necessità di farmaco concomitante che è un forte inibitore del citocromo P450 (CYP) 3A4

E.5 End points

E.5.1

Primary end point(s)

Overall survival: The primary objective of this trial is to compare OS of subjects receiving standard of care treatment (GEM) plus dasatinib
versus GEM plus placebo. Subjects will be followed after discontinuation
of study therapy to record time to death. The final analysis will be conducted after 135 subject deaths.

Sopravvivenza globale: l'obiettivo principale di questo studio è confrontare la OS dei soggetti che ricevono il trattamento di cura standard (GEM) più dasatinib. rispetto a l trattamento GEM più placebo.
I pazienti saranno seguiti dopo la discontinuazione della terapia in studio per registrare la data del decesso. L'analisi finale sarà eseguita dopo che si sono verificati 135 decessi.

E.5.1.1

Timepoint(s) of evaluation of this end point

The final analysis will be conducted
after 135 subject deaths.

L'analisi finale sarà eseguita dopo che si sono verificati 135 decessi.

E.5.2

Secondary end point(s)

Progression Free Survival: Subjects will be assessed by imaging after
every 2 cycles (ie, Weeks 8, 16, 24, etc). Progression events will be
investigator determined according to Response
Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria. Worsening pain,
fatigue, ECOG PS, and/or CA19-9 are not by themselves considered
evidence of disease progression
but may be considered in the investigator's evaluation of disease.
• Safety: All AEs will be recorded with onset date, resolution or
stabilization date, severity grade, and relatedness to study treatment.

- Sopravvivenza libera da malattia: i soggetti saranno valutati mediante diagnostica per immagini dopo ogni 2 cicli (cioè, Settimane 8, 16, 24, ecc.) Gli eventi di progressione sarnno
determinati dallo sperimentatore in base alla Risposta.
Evaluation Criteria in Solid Tumor (RECIST) criterio 1.1. Peggioramento del dolore, affaticamento, ECOG PS, e / o CA19-9 non sono di per sé considerati evidenza di progressione di malattia, ma possono essere considerate nella valutazione della malattia da parte dello sperimentatore.
• Sicurezza: tutti eventi avversi saranno registrati con la data inizio, data di risoluzione o data di stabilizzazione, grado di gravità, e correlazione con il trattamento in studio.

E.5.2.1

Timepoint(s) of evaluation of this end point

Progression Free Survival: every 2 cycles

Sopravvivenza libera da malattia: ogni due cicli

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

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

CA19-9 response will be analyzed

sarà misurato il livello di CA19-9 nel siero

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)

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

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.8.5.1

Number of sites anticipated in the EEA

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

Canada

Russian Federation

South Africa

United States

E.8.7

Trial has a data monitoring committee

Yes

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

The End of Trial Date will be determined by the sponsor after at least 135 death events have occurred.

LA conclusione della sperimentazione sarà determinata dallo sponsor dopo che si sono verificati almeno 135 decesi

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:

120

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

F.3.3.2

Women of child-bearing potential using contraception

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

130

F.4.2.2

In the whole clinical trial

200

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)

Patients remaining on the study after the final study analysis is conducted, once 135 deaths have occured, will be offered commercially available Dasatinib depending on the availability within their country

I soggetti possono continuare a ricevere la terapia sperimentale fino all'esecuzione dell'analisi finale dello studio dopo che si sono verificati 135 decessi. I soggetti che hanno ricevuto la terapia sperimentale fino a quel momento, possono ricevere forniture commerciali a discrezione dello sperimentatore secondo le indicazioni cliniche.

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

2011-09-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-06-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-06-15

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