Clinical Trials Register

Summary
EudraCT Number:	2015-004028-69
Sponsor's Protocol Code Number:	IRIBIL
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-10-04
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

Germany - BfArM

A.2

EudraCT number

2015-004028-69

A.3

Full title of the trial

5-Fluorouracil (5-FU), folinic acid and irinotecan (FOLFIRI) versus 5-FU and folinic acid as second-line chemotherapy in patients with biliary tract cancer (IRIBIL): a randomized open-label phase 2 study

5-Fluoruracil (5-FU), Folinsäure und Irinotecan (FOLFIRI) versus 5-FU und Folinsäure als Zweitlinienchemotherapie bei Patienten mit Karzinomen des biliären Systems: eine randomisierte offene Phase 2-Studie (IRIBIL)

A.3.1

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

A.4.1

Sponsor's protocol code number

IRIBIL

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	Goethe-Universität Frankfurt, PD Fabian Finkelmeier
B.1.3.4	Country	Germany
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	Medac
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Universitäres Centrum für Tumorerkrankungen Frankfurt
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medizinische Klinik 1, Universitätsklinikum der Goethe-Universität Frankfurt
B.5.2	Functional name of contact point	Studienambulanz Prof. Zeuzem
B.5.3	Address:
B.5.3.1	Street Address	Theodor-Stern-Kai 7
B.5.3.2	Town/ city	Frankfurt
B.5.3.3	Post code	60590
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49(0)696301-87769
B.5.5	Fax number	+49(0)6963016580
B.5.6	E-mail	Fabian.Finkelmeier@kgu.de

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.2.5	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	Irinotecan
D.3.4	Pharmaceutical form	Concentrate for 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	Irinotecan
D.3.9.1	CAS number	136572-09-3
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/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	180
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	Yes
D.3.11.13.1	Other medicinal product type	cytostatic drug
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Oncofolic
D.2.1.1.2	Name of the Marketing Authorisation holder	medac
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.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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	Comparator
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	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.3.4	Pharmaceutical form	Solution for injection
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	5-Fluorouracil
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/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

biliary tract cancer not amedable for curative resection with progressive disease after first-line chematherapy with gemcitabine and cisplatin

Metastasierte oder lokal fortgeschrittene, nicht operable Tumoren des biliären Systems (Gallengangs-, Gallenblasen- sowie Papillenkarzinome), die eine progrediente Erkrankung unter einer Erstlinienchemotherapie mit Gemcitabin- und platinhaltigen Chemotherapie zeigten.

E.1.1.1

Medical condition in easily understood language

Patients suffering from cholangiocarinoma or gallbladder cancer without possibility for resection and disease progress after therapy with gemcitabine and cisplatin.

Fortgeschrittener Tumor der Gallenblase oder -wege, der nicht operiert werden kann. Nach Chemotherapie mit Gemcitabin und einem Platinderivat kam es zu einem Voranschreiten der Erkrankung.

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

• Determination of the progression free survival (PFS) in FOLFIRI arm > 2 months

E.2.2

Secondary objectives of the trial

Determination of
• overall survival (OS)
• time to progression (TTP) by RECIST 1.1
• overall response rate (either complete response, CR, or partial response, as measured by RECIST 1.1
• safety profile
• quality of life (EORTC QLQ-C30 questionnaire)

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Translation Research Program (see section 12.3. in the protocol).

E.3

Principal inclusion criteria

• Written informed consent granted prior to initiation of any study specific screening procedures
• Patients with histologically confirmed CCA or GB-CA not suitable for resection or metastatic
• Progressive disease undergoing a systemic chemotherapy with a platin-derivate (Oxaliplatin, Cisplatin or Carboplatin) or progressive disease within 3 months after cessation of chemotherapy
• Age >= 18 years
• Performance status ECOG 0-2
• Normal organ and bone marrow function defined as:
o Hematopoetic: absolute neutrophil count >1,500/mm3, platelet count >75,000/mm3, hemoglobin >9 g/dL
o INR ≤ 1.5
o Hepatic: AST or ALT < 5 x ULN, bilirubin ≤ 2 mg/dl
o Renal: serum creatinine < 1.5 x ULN
• Child Pugh stage A in patients with cirrhosis
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the randomization
• Male or female patients of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received

E.4

Principal exclusion criteria

• CCA or GB-CA amendable for surgical resection
• Prior radiation therapy, chemoradiation, transarterial chemoembolisation (TACE), Radiofrequency ablation (RFA) or selective intraarterial Radiotherapy (SIRT) within the last 3 months, radiation of symptomatic bone metastasis is allowed
• Concomitant photodynamic therapy or intraductal radiofrequency ablation within the last 8 weeks
• Child Pugh stage B or C (> 6 points) in patients with cirrhosis (Appendix 21.3)
• Massive, uncontrolled ascites
• Systemic anticancer chemotherapy other than Gemcitabin and a platin derivate (Cisplatin, Carboplatin or Oxaliplatin)
• Cardiac disease: congestive heart failure > class II NYHA
• Known uncontrolled brain metastasis
• History of bone marrow or organ allograft
• Active clinically serious infections > CTCAE grade 2 beside of chronic hepatitis C virus infection
• Major surgery within 4 weeks of first dose of study drug, port implantation is allowed
• Known or suspected allergies to 5-FU, folinic acid or irinotecan
• Previous cancer that is distinct in primary site or histology from CCA or GB-CA except cervical cancer in situ, treated basal cell carcinoma, superficial bladder tumors or any cancer curatively treated 3 years prior to study entry
• Substance abuse, medical or psychological condition that may interfere with the patient´s participation in the study
• Participation in another clinical trial with any investigational study drug (whatever the use, curative, prophylactic or diagnostic intent) within 30 days prior to enrollment
• Pregnancy or breast feeding women
• Incapability to give valid informed consent (including patients who are dependent on the sponsor or the investigator)

E.5 End points

E.5.1

Primary end point(s)

Determination of the progression free survival (PFS) in FOLFIRI arm > 2 months

E.5.1.1

Timepoint(s) of evaluation of this end point

every 8 weeks

E.5.2

Secondary end point(s)

- overall survival (OS)
- time to progression (TTP) by RECIST 1.1
- overall response rate (either complete response, CR, or partial response, as measured by RECIST 1.1
- safety profile
- quality of life (EORTC QLQ-C30 questionnaire)

E.5.2.1

Timepoint(s) of evaluation of this end point

- overall survival (OS): every visit
- time to progression (TTP) by RECIST 1.1: every 8 weeks
- overall response rate (either complete response, CR, or partial response, as measured by RECIST 1.1: every 8 weeks
- safety Profile: every visit
- quality of life (EORTC QLQ-C30 questionnaire): every 2 weeks

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

Yes

E.6.13.1

Other scope of the trial description

Translational Research Program:
Additonal blood samples for translational research will be taken if patient gives consent.

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

comparison to standard therapy with 5-Fluorouracil (5-FU) and Folinicc Acid

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

The end of the trial is reached if all patients finished the follow-up period which starts 30 days after the last study treatment administration until death. survival Information will be collected every 6 weeks.

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)

None, since patients will be treated according to normal treatment of that condition.

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

2016-12-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-09-13

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

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