Clinical Trials Register

Summary
EudraCT Number:	2013-003830-34
Sponsor's Protocol Code Number:	415-13
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:	2013-09-25
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

2013-003830-34

A.3

Full title of the trial

Pleurectomy/decortication and hypterthermic intrathoracic chemotherapy compared to pleurectomy/decortication in patients with malignant pleural mesothelioma

Pleurektomie/Dekortikation und hypertherme intrathorakale Chemotherapie (HITHOC) versus Pleurektomie/Dekortikation bei malignem Pleuramesotheliom

A.3.1

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

Thoracic Mesothelioma: Surgery with or without subsequent lavage at high temperature with addition of chemotherapy

Pleuramesotheliom: Operation mit oder ohne anschließender Spülung bei erhöhter Temperatur mit Zusatz von Chemotherapeutika

A.3.2

Name or abbreviated title of the trial where available

HITHOC

A.4.1

Sponsor's protocol code number

415-13

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	Asklepios Fachkliniken München Gauting
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	Deutsches Zentrum für Lungenforschung
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	Asklepios Fachkliniken München-Gauting
B.5.2	Functional name of contact point	Klinik für Thoraxchirurgie
B.5.3	Address:
B.5.3.1	Street Address	Robert-Koch-Allee 2
B.5.3.2	Town/ city	Gauting
B.5.3.3	Post code	82131
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4989857914207
B.5.5	Fax number	+4989857914206
B.5.6	E-mail	m.lindner@asklepios.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	Cisplatin
D.2.1.1.2	Name of the Marketing Authorisation holder	Teva
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	Cisplatin Teva
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	Intrapleural use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Cisplatin
D.3.9.1	CAS number	15663-27-1
D.3.9.2	Current sponsor code	Cis
D.3.9.3	Other descriptive name	CISPLATIN
D.3.9.4	EV Substance Code	SUB07483MIG
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	1mg/ml
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

malignant pleuramesothelioma

malignes Pleuramesotheliom

E.1.1.1

Medical condition in easily understood language

malignant pleural mesothelioma

malignes Pleuramesotheliom

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	16.1
E.1.2	Level	PT
E.1.2	Classification code	10027407
E.1.2	Term	Mesothelioma malignant
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Malignant pleural mesothelioma is a yet uncurable disease, with a
median survival of 9 months after diagnosis. Treatment is usually
multimodulary, including operation, chemotherapy and radiation.
HITHOC (hyperthermic intrathrocic chemotherapy) with cisplatin and
doxorubicin is used to enhance lokal tumor control after pleurectomy
and decortication. In some patients, survival of 2 years can be achieved.
However, the chemotherapeutics can have severe lokal and systemic
side effects. No data exist to which extend hyperthermia and
chemotherapy add to the beneficial effect. The aim of this study is to compare the standard surgical procedure followed by HITHOC therapy to the standard surgery alone and thus identify the therapeutic
option of sufficient effectivity with reduced side effects. Disease-free
and overall survival, therapy induced morbidities and quality of life will
be documented.

Das Pleuramesotheliom ist eine unheilbare maligne Erkrankung, mit
einer mittleren Überlebenszeit von 9 Monaten nach Diagnose. Die
Behandlung erfolgt i.d.R. multimodular mit Operation, Chemotherapie
und Radiotherapie. HITHOCH (hypertherme, intrathorakale
Chemotherapie) mit Cisplatin und Doxorubin wird zur lokalen
Tumorkontrolle nach Operation (Pleurektomie und Dekortikation)
eingesetzt. In einigen Patienten können Überlebenszeiten bis zu 2
Jahren erreicht werden. Es gibt jedoch keine Daten darüber, welchen
Beitrag hierzu die Hyperthermie und welchen die Chemotherapie leistet. Das Ziel dieser Studie ist es, das Standard-OP-Verfahren gefolgt von HITHOC Therapie zur Standard Operation allein zu vergleichen und so eine ausreichend effektive Therapie mit den geringstmöglichen
Nebenwirkungen zu beschreiben. Krankheitsfreies und
Gesamtüberleben, Nebenwirkungen und Lebensqualität werden
dokumentiert.

E.2.2

Secondary objectives of the trial

not applicable

trifft nicht zu

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients age ≤ 80 years
epithelioid pleural mesothelioma
P3D is not possible or desired
Ph. I-II; Ph. III (T1-T2 N1/N2 no LK-bulks)
Diagnosis by biopsy VATS + Biopsy
ECOG performance status 0-1
Creatinine <1.2 mg / dl, GFR> 60 ml / min
no relevant KHK
no other primary therapy
signed consent form

Patientenalter ≤ 80 Jahre
epitheloides Pleuramesotheliom
P3D nicht möglich oder nicht gewünscht
Stad. I-II; Stad III (T1-T2 N1/N2 keine LK-bulks)
Diagnosestellung durch VATS + Biopsie
ECOG Performance-Status 0-1
Kreatinin < 1,2 mg/dl, GFR > 60 ml/min
keine relevante KHK
keine andere Primärtherapie
signierte Einverständniserklärung

E.4

Principal exclusion criteria

no signed informed consent
inoperable
Health does not allow the application of local chemotherapy and hyperthermia

Cisplatin is contraindicated in patients:
with a hypersensitivity to cisplatin, other platinum-containing drugs
or any of the excipients
with renal dysfunction (creatinine clearance <60ml/min)
which are in a dehydrated state (used to prevent serious
Impaired renal function before and after the application of a hydrogenation
required)
with myelosuppression
with a hearing impairment
with cisplatinbedingter neuropathy
the silent
in combination with yellow fever vaccine and prophylactic phenytoin inserted

keine Einverständniserklärung
nicht operabel
Gesundheitszustand lässt die Anwendung einer lokalen Chemotherapie und Hyperthermie nicht zu

Cisplatin ist kontraindiziert bei Patienten:
mit einer Überempfindlichkeit gegen Cisplatin, anderen platinhaltigen Arzneimitteln
oder einen der sonstigen Bestandteile
mit einer renalen Dysfunktion (Kreatinin-Clearance <60ml/min)
die sich in dehydriertem Zustand befinden (zur Vorbeugung einer schwerwiegenden
Nierenfunktionsstörung ist vor und nach der Anwendung eine Hydrierung
erforderlich)
mit einer Myelosuppression
mit einer Beeinträchtigung des Gehörs
mit cisplatinbedingter Neuropathie
die stillen
in Kombination mit Gelbfieberimpfstoff und prophylaktisch eingesetztem Phenytoin

E.5 End points

E.5.1

Primary end point(s)

overall survival

Gesamtüberleben

E.5.1.1

Timepoint(s) of evaluation of this end point

2 years after inclusion of the last patient

2 Jahre nach Einschluss des letzten Patienten

E.5.2

Secondary end point(s)

disease free survival
morbidiy
quality of life

krankheitsfreies Überleben
Morbidität
Lebensqualität

E.5.2.1

Timepoint(s) of evaluation of this end point

every 3 months

alle 3 Monate

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Surgery only

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

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

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)

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)

After the end of the study or after premature withdrawal patients will be treated according to the guideline for the treatment of malignant pleural mesothelioma and according to the progression of the disease. Subsequent treatment is independent of the participation in this study.

Nach Beendigung der Studie oder nach einem frühzeitige Ausscheiden aus der Studie werden die Patienten entsprechend den Richtlinien für die Behandlung eines malignen Pleuramesothelioms und entsprechend des Fortschreitens ihrer Erkrankung weiterbehandelt. Die Weiterbehandlung ist unabhängig von der Studienteilnahme.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Deutsches Zentrum für Lungenforschung - DZL
G.4.3.4	Network Country	Germany

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-05-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-12-16

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

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