Clinical Trials Register

Summary
EudraCT Number:	2019-000922-23
Sponsor's Protocol Code Number:	IRITACE
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-01-31
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

Germany - BfArM

A.2

EudraCT number

2019-000922-23

A.3

Full title of the trial

Transarterial chemoembolization (TACE) with Irinotecan and Mitomycin C versus TACE with Doxorubicin in patients with Hepatocellular carcinoma not amenable to curative treatment - IRITACE- a randomized multicenter phase 2 trial. A trial of the German Alliance for Liver Cancer (GALC)

Transarterielle Chemoembolization (TACE) mit Irinotecan und Mitomycin C im Vergleich zu TACE mit Doxorubicin bei Patienten mit nicht kurativ behandelbarem Hepatozellulärem Karzinom - IRITACE - eine randomisierte Multizentrische Phase 2 Studie. Eine Studie der „German Alliance for Liver Cancer“ (GALC).

A.3.1

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

Image-guided, non-surgical procedure in combination with different chemotherapeutics in patients with Hepatocellular carcinoma not amenable to curative treatment

Minimalinvasives, radiologisches Verfahren in Kombination mit verschiedenen Chemotherapeutika zur Behandlung von Patienten mit nicht heilbarem Hepatozellulärem Karzinom

A.3.2

Name or abbreviated title of the trial where available

TACE with Irinotecan and Mitomycin C in HCC

TACE mit Irinotecan und Mitomycin C in HCC

A.4.1

Sponsor's protocol code number

IRITACE

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
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	Else-Kröner-Fresenius-Stiftung
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	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	Steinbacher Hohl 2-26
B.5.3.2	Town/ city	Frankfurt
B.5.3.3	Post code	60488
B.5.3.4	Country	Germany
B.5.6	E-mail	iritace@ikf-khnw.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.2.1.2	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	Irinotecan
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	Local use (Noncurrent)
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	97682-44-5
D.3.9.4	EV Substance Code	SUB08295MIG
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.2.1.2	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	Mitomycin C
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	Local use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MITOMYCIN
D.3.9.1	CAS number	50-07-7
D.3.9.4	EV Substance Code	SUB09006MIG
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.2.1.2	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	Doxorubicin
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	Local use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DOXORUBICIN
D.3.9.1	CAS number	23214-92-8
D.3.9.4	EV Substance Code	SUB06391MIG
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 Hepatocellular carcinoma not amenable to curative treatment

E.1.1.1

Medical condition in easily understood language

Patients with Hepatocellular carcinoma not amenable to curative treatment

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	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10029104
E.1.2	Term	Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10007416
E.1.2	Term	Carcinoma liver
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10019828
E.1.2	Term	Hepatocellular carcinoma non-resectable
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

Determination of the progression free survival (PFS) time

E.2.2

Secondary objectives of the trial

Determination of
– overall survival (OS)
– response/disease control rate (DCR) (either complete response, CR, or partial response, as measured by mRECIST for HCC)
– time to progression
– time to macrovascular invasion/extrahepatic spread (MVI/EHS)
– time to unTACEable progression
– safety profile
– quality of life (as measured by FACT-Hep and FACT-G7 questionnaires)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent granted prior to initiation of any study specific screening procedures
2. Patients with histologically confirmed HCC primarily not suitable for resection, ablation or liver transplantation. A combined therapy with TACE and subsequent ablation is possible.
3. Availability of Biopsy for translational research, if patients give their consent
4. Absence of extrahepatic spread
5. Age >/= 18 years
6. Patients with measurable disease according to mRECIST
7. Performance status ECOG 0 and 1 (Appendix 20)
8. Normal organ and bone marrow function defined as:
– Hematopoetic: absolute neutrophil count ≥ 1,500/mm3, platelet count ≥ 60 x 109/l, hemoglobin ≥ 9 g/dL
– INR ≤ 1.5 x ULN
– Hepatic: AST and ALT < 5 x ULN, bilirubin ≤ 2 mg/dl
– Renal: serum creatinine ≤ 1.5 x ULN
9. Child-Pugh stage A
10. Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to enrolment
11. Male or female patients of child-bearing potential must agree to use oral contraception, intrauterine device, bilateral tubal occlusion, vasectomized partner or avoidance of intercourse during the study and for 180 days after last investigational drug dose received

E.4

Principal exclusion criteria

1. Extrahepatic tumor manifestation
2. Tumor infiltration of more than 50% of the whole liver mass
3. Infiltration or thrombosis of the main portal vein or the main left or right intrahepatic branches
4. Child Pugh status B or C > 6 points according to Child Pugh classification (Appendix 20)
5. Prior TACE or selective intraarterial Radiotherapy (SIRT)
6. Prior systemic anticancer therapy for HCC
7. Life expectancy of less than 12 weeks
8. Esophageal varices grade III (any) or esophageal varices grade II with increased risk for bleeding (red wale signs, cherry spots, red coloration, hematocystic spots) without prophylactic band ligation
9. Known or suspected manifest hyperthyroidism
10. Congestive heart failure > class II NYHA (Appendix 20)
11. Cardiac ventricular arrhythmias requiring antiarrhythmic therapy, acute myocardial infarction, myocardial infarction, acute inflammatory heart disease > CTCAE grade 2 within the past 6 months (Appendix 20)
12. Previous treatment with doxorubicin up to the maximum lifetime dose of 550mg/m2
13. History of organ allograft or bone marrow transplantation
14. Active uncontrolled clinically serious infections > CTCAE grade 2 except chronic hepatitis C infection (Appendix 20)
15. Severe restrictive or obstructive lung disease
16. Clinically apparent chronic inflammatory bowel disease and/or ileus
17. Hemorrhage/bleeding event or variceal bleeding > CTCAE grade 2 within 4 weeks of first dose of study drug (Appendix 20)
18. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug
19. Known or suspected allergies to Iodine-containing or Gadolinum-containing contrast medium, Irinotecan, Mitomycin C, Doxorubicin or other inactive ingredients of the drugs
20. Previous cancer that is distinct in primary site or histology from HCC except cervical cancer in situ, treated basal cell carcinoma, superficial bladder tumors or any cancer curatively treated 3 years prior to study entry
21. Concomitant treatment with St. John's wort
22. Substance abuse, medical, psychological or social condition that may interfere with the patient´s participation in the study
23. Participation in another clinical trial with any investigational study drug (whatever the use, curative, prophylactic or diagnostic intent) within 30 days prior to enrollment
24. Incapability to give valid informed consent (including patients who are dependent on the sponsor or the investigator)
25. Pregnancy or breast-feeding women

E.5 End points

E.5.1

Primary end point(s)

Progression free survival (PFS) time

E.5.1.1

Timepoint(s) of evaluation of this end point

continuously

E.5.2

Secondary end point(s)

– overall survival (OS)
– response/disease control rate (DCR) (either complete response, CR, or partial response, as measured by mRECIST for HCC)
– time to progression
– time to macrovascular invasion/extrahepatic spread (MVI/EHS)
– time to unTACEable progression
– safety profile
– quality of life (as measured by FACT-Hep and FACT-G7 questionnaires)

E.5.2.1

Timepoint(s) of evaluation of this end point

continuously

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

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

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

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

Database closure is defined as the end of the trial: Sites need to collect
survival data of patients and are involved in the data cleaning process
actively (e.g. additional source data may be requested and additonal
monitoring visits may be neccessary). Therefore, database closure is
considered the end of the trial.

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

104

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 will continue with TACE treatment every 8 weeks as long as there is a benefit and dynamic imaging shows hypervascularity of the tumor nodules for up to 18 months. After termination of the study treatment due to whatever reason, treatment of the individual patient will be continued outside the trial at the treating physician’s discretion

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

2020-02-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-01-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-11-22

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