Clinical Trials Register

Summary
EudraCT Number:	2017-004675-31
Sponsor's Protocol Code Number:	AMCmedonc17-010
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-10-15
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

Austria - BASG

A.2

EudraCT number

2017-004675-31

A.3

Full title of the trial

A randomized Phase II study of second line treatment with liposomal irinotecan and S1 versus liposomal irinotecan and 5-fluorouracil in patients with metastatic pancreatic cancer who failed on first line gemcitabine-based chemotherapy

Een gerandomiseerd fase II onderzoek met liposomaal irinotecan in combinatie met S1 in vergelijking met liposomaal irinotecan en 5-Fluorouracil bij patiënten die eerder behandeling hebben gehad met een op gemcitabine gebaseerd regime voor alvleesklierkanker

A.3.1

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

Randomised study for second line treatment with nal-IRI and S1 in pancreatic cancer.

2e lijns studie met nal-IRI en S1 voor patiënten met alvleesklierkanker

A.4.1

Sponsor's protocol code number

AMCmedonc17-010

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	Academic Medical Center
B.1.3.4	Country	Netherlands
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 of Amsterdam
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Academic Medical Center
B.5.2	Functional name of contact point	Eva van Daalen
B.5.3	Address:
B.5.3.1	Street Address	Meibergdreef 9
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1105 AZ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31205668229
B.5.5	Fax number	+31206919743
B.5.6	E-mail	trialmedonc@amc.nl

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	ONIVYDE
D.2.1.1.2	Name of the Marketing Authorisation holder	Les Laboratoires Servier
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	onivyde
D.3.2	Product code	EMA/515476/2016
D.3.4	Pharmaceutical form	Powder for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Auricular use Intraamniotic use Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Irinotecanhydrochlorid
D.3.9.1	CAS number	97682-44-5
D.3.9.2	Current sponsor code	Irinotecanhydrochlorid
D.3.9.3	Other descriptive name	IRINOTECAN HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB02772MIG
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	4,3
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	Teysuno
D.2.1.1.2	Name of the Marketing Authorisation holder	Nordic Group BV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	teysuno
D.3.2	Product code	EMA/20503/2012
D.3.4	Pharmaceutical form	Capsule
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	TEGAFUR
D.3.9.1	CAS number	150863-82-4
D.3.9.2	Current sponsor code	tegafur
D.3.9.4	EV Substance Code	SUB10870MIG
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	15
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GIMERACIL
D.3.9.1	CAS number	103766-252
D.3.9.3	Other descriptive name	GIMERACIL
D.3.9.4	EV Substance Code	SUB21055
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	4,35
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OTERACIL POTASSIUM
D.3.9.1	CAS number	2207-75-2
D.3.9.3	Other descriptive name	OTERACIL POTASSIUM
D.3.9.4	EV Substance Code	SUB21056
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	11,8
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: 3
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	fluorouracil
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare Limited,
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	5 fluorouracil
D.3.2	Product code	EMA/706456
D.3.4	Pharmaceutical form	Solution 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	fluorouracil
D.3.9.1	CAS number	51-21-8
D.3.9.2	Current sponsor code	fluorouracil accord
D.3.9.3	Other descriptive name	FLUOROURACIL
D.3.9.4	EV Substance Code	SUB07721MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

pancreatic cancer

pancreas kanker

E.1.1.1

Medical condition in easily understood language

pancreatic cancer

alvleesklier kanker

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

Run in phase: Dose limiting toxicity (DLT) and Maximal tolerated dose (MTD) of nal-IRI when co-administered with fixed dose S1 in patients with metastatic pancreatic cancer.
Phase II part: Efficacy between the treatment arms in terms of progression free survival.

fase I deel: vaststellen maximaal tolereerbare dosis en dosis limiterende bijwerkingen, als nal-IRO wordt toegevoegd aan S1
fase II deel: effectiviteit van de behandeling met nal-IRI en S1, uitgedrukt in progressie vrije overleving

E.2.2

Secondary objectives of the trial

Overall survival
Response rate according to RECIST 1.1
Adverse events according to NCI CTC version 4.0
Quality of life

Overall survival
Response rate volgens RECIST 1.1
Adverse events volgens NCI CTC versie 4.0
Kwaliteit van leven

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Able to understand and provide written informed consent
≥ 18 years of age
Histologically or cytologically confirmed adenocarcinoma of exocrine pancreas
Documented metastatic disease
Previously treated with gemcitabine or gemcitabine containing therapy, or progression within 6 months of adjuvant gemcitabine treatment
Adequate hepatic, renal and hematological function
Caucasian

In staat zijn een informed consent te begrijpen en te tekenen
≥ 18 jaar
Histologisch of cytologisch bewezen adenocarcinoom van de pancreas
Gemetastaseerde ziekte
Eerder behandeld met gemcitabine of een gemcitabine bevattende therapie, of binnen 6 maanden na stop adjuvant gemcitabine progressie van ziekte
Goede lever-, nier en beenmergfunctie
Caucasisch

E.4

Principal exclusion criteria

KPS < 70
Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 2
Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months
NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings
Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician’s opinion might compromise the patient’s health
Current use or any use in last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
Known hypersensitivity to any of the components of liposomal irinotecan (nal-IRI) other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.
Hypersensitivity to any of the active substances (tegafur, gimeracil, and oteracil)
History of severe and unexpected reactions to fluoropyrimidine therapy
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use a reliable method of birth control, during therapy and for 3 months following the last dose of liposomal irinotecan (nal-IRI).
Treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine

KPS < 70
Klinisch significante gastro-intestinale aandoening (o.a. hepatitis, bloedingen, inflammatie, diarree > graad 2)
Ernstige arteriele thromboembolische gebeurtenissen in de afgelopen 6 maanden (myocard infarct, instabiele angina pectoris, herseninfarct)
NYHA klasse III or IV congestief hartfalen, ventriculaire arrhythmieen of oncontroleerbare bloeddruk, afwijkend ECG, wat klinisch significant Active infectie of niet verklaarde temperatuur >38.5°C (excluding tumor feverexclusief tumor koorts)
CYP3A-enzym inducers/inhibitors en/of sterke UGT1A inhibitors
Bekende overgevoeligheid voor (een onderdeel van) liposomaal irinotecan (nal-IRI), irinotecan, fluoropyrimidines, en/ of leucovorin.
Hypersensitivity to any of the active substances (tegafur, gimeracil, and oteracil)
In de voorgeschiedenis onverwachte reactie op fluoropyrimidine behandeling
Bekende dihydropyrimidine dehydrogenase (DPD) deficientie
Borst voeding, zwangerschap, postieve zwangerschapstest, niet bereid om voorzorgsmaatregelen te nemen om zwangerschap te voorkomen.
Behandeling met DPD emmers in de afgelopen 4 weken.

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluation with CTscan/ MRI will take place every 2 months

Evaluatie met behulp van en CTscan/ MRI vindt iedere 2 weken plaats

E.5.2

Secondary end point(s)

Overall survival
Response rate according to RECIST 1.1
Adverse events according to NCI CTC version 4.0
Quality of life

Overall survival
Response rate volgens RECIST 1.1
Adverse events volgens NCI CTC versie 4.0
Kwaliteit van leven

E.5.2.1

Timepoint(s) of evaluation of this end point

Evaluation with CTscan/ MRI will take place every 2 months
Adverse events will be evaluated every 2 weeks
Quality of life will be evaluated every 2 months

Evaluatie met behulp van en CTscan/ MRI vindt iedere 2 weken plaats
Bijwerkingen worden iedere 2 weken geevalueerd
Kwaliteit van leven wordt iedere 2 maanden geevalueerd

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

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

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

Yes

E.8.2.3.1

Comparator description

liosomal irinotecan and 5-fluorouracil

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.8.4.1

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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

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:

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

F.4.2.2

In the whole clinical trial

120

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)

Follow up for late toxicity every 8 weeks and report date of death

Volgen voor late toxiciteit elke 8 weken en datum van overlijden rapporteren

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

2019-11-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-10-25

P. End of Trial
P.	End of Trial Status	Ongoing

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