Clinical trial • Phase III • Oncology

ETOPOSIDE for Malignant extracranial germ cell tumours

Phase III trial of ETOPOSIDE for Malignant extracranial germ cell tumours.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Malignant extracranial germ cell tumours
Trial Stage
Phase III
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
16-09-2024
First CTIS Authorization Date
15-10-2024

Trial design

Randomised, randomized comparison of carboplatin (600 mg/m² per cycle / auc 7.9 mg/ml/min.) versus cisplatin (100 mg/m² per cycle).-controlled Phase III trial in Germany, Netherlands, Austria.

Randomised
Yes
Comparator
Randomized comparison of Carboplatin (600 mg/m² per cycle / AUC 7.9 mg/ml/min.) versus Cisplatin (100 mg/m² per cycle).
Target Sample Size
350

Eligibility

Recruits 350 paediatric patients.

Pregnancy Exclusion
Pregnancy
Vulnerable Population
The trial includes a paediatric population (patients up to 17 11/12 years and ovarian primaries up to 29 11/12 years). Written informed consent of patients and/or their parents according to national law is required prior to trial entry. Subject information and informed consent forms are available for different age groups (e.g. adults, parents/custodians, 12-17 years, 0-12 years) as documented in the submitted ICF/SIS documents for participating Member States.

Inclusion criteria

  • {"criterion_text":"- Confirmed extracranial MGCT up to 17 11/12 years of age or patients with ovarian primaries up to 29 11/12 years of age on the date of written informed consent\n- Diagnosis of a chemotherapy-naïve extracranial MGCT\n- Written informed consent of patients and/or their parents according to national law prior to trial entry\n- Karnofsky-Index of >70% or ECOG-Status 0-II\n- Negative pregnancy test within 7 days prior to starting treatment for female patients of childbearing potential, in case of ß-HCG secreting MGCT pregnancy has to be excluded by appropriate methods"}

Exclusion criteria

  • {"criterion_text":"- Pregnancy\n- Lactation\n- Incomplete data at trial entry preventing risk group allocation\n- HIV-positivity (does not apply to low risk patients, but must be available before randomisation)\n- Live vaccine immunization within two weeks before start of protocol treatment\n- Sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 12 months after end of chemotherapy\n- Current or recent (within 30 days prior to date of informed written consent) treatment with another investigational drug or participation in another interventional clinical trial, except trials with different end points than MAKEI V that can run in parallel to MAKEI V without influencing that trial, e.g., trials on antiemetics, antimycotics, antibiotics, strategies for psychosocial support, etc.\n- Any other medical, psychiatric or drug related condition, or social condition incompatible with protocol treatment\n- Actual audiometry not available ( does not apply to low risk patients)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Event-free survival, defined as minimum time from the date of randomization to the following events (EFSr): • Death from any cause • Progressive disease, defined as increase of standard tumour marker with or without expansion of tumour mass/metastases • Viable tumour cells at time of final surgery • Relapse • Second malignancy • or the date of the last follow-up This relates to patients randomized to Carboplatin or Cisplatin.","definition_or_measurement_approach":"EFSr defined as minimum time from date of randomization to any of: death from any cause; progressive disease (increase of standard tumour marker with or without expansion of tumour mass/metastases); viable tumour cells at time of final surgery; relapse; second malignancy; or date of last follow-up. Applies to patients randomized to Carboplatin or Cisplatin."}

Secondary endpoints

  • {"endpoint_text":"- Event-free survival (EFS), defined as minimum time from the date of diagnosis to any of the events described above or to last follow-up, of all patients included in MAKEI V in respect to the defined MAKEI V risk groups","definition_or_measurement_approach":"EFS defined from date of diagnosis to same events as primary EFS or last follow-up; analysed for all patients by defined MAKEI V risk groups."}
  • {"endpoint_text":"- Overall survival (OS), defined as minimum time from the date of diagnosis to death of any cause or to last follow-up, of all patients included in MAKEI V in respect to the defined MAKEI V risk groups","definition_or_measurement_approach":"OS defined from date of diagnosis to death from any cause or last follow-up; analysed across MAKEI V risk groups."}
  • {"endpoint_text":"- Health economic parameter, e.g. hospitalization days during treatment, number of blood transfusions, in respect to treatment with Carboplatin or Cisplatin","definition_or_measurement_approach":"Health economic measures include hospitalization days during treatment and number of blood transfusions, compared between Carboplatin and Cisplatin arms."}
  • {"endpoint_text":"- Short and late toxicities according to CTCAE v5.0","definition_or_measurement_approach":"Toxicity graded and recorded using CTCAE v5.0 for acute and late events."}
  • {"endpoint_text":"- Assessment of safety: Adverse events and laboratory abnormalitie, CTCAE v5.0 grade, timing, seriousness and relatedness.","definition_or_measurement_approach":"Safety assessed by recording adverse events and laboratory abnormalities with CTCAE v5.0 grading, timing, seriousness and causality."}
  • {"endpoint_text":"- Fertility relevant endocrine outcomes, e.g. Estrogen, AMH, LH, FSH, Inhibin B.","definition_or_measurement_approach":"Assessment of endocrine markers relevant to fertility (e.g. Estrogen, AMH, LH, FSH, Inhibin B) as specified in protocol."}
  • {"endpoint_text":"- Patient reported outcomes including HRQoL, fatigue, sexual function and fertility outcomes (in adult patients)","definition_or_measurement_approach":"PROs collected including health-related quality of life, fatigue; additional sexual function and fertility outcomes for adult patients."}
  • {"endpoint_text":"- Determination of risk for relapse in respect to used surgical intervention","definition_or_measurement_approach":"Analysis of relapse risk relative to surgical procedures used, using standardized surgical documentation."}
  • {"endpoint_text":"- Radiological response rate after two (and if applicable four) cycles of either Carboplatin or Cisplatin chemotherapy","definition_or_measurement_approach":"Radiological response assessed after two (and if applicable four) cycles of chemotherapy; response criteria as per protocol/radiology section."}
  • {"endpoint_text":"- Standard tumour marker levels after every cycle of either Carboplatin or Cisplatin chemotherapy","definition_or_measurement_approach":"Tumour marker kinetics measured after every chemotherapy cycle using standard tumour markers."}

Recruitment

Registry Or Advocacy Recruitment
True, Deutsche Krebshilfe; registered in DRKS (DRKS00019921)
Planned Sample Size
350
Recruitment Window Months
108
Consent Approach
Written informed consent of patients and/or their parents according to national law prior to trial entry. Age-specific subject information and informed consent forms are provided (examples: adults, parents/custodians, 12-17 years, 0-12 years) as documented in the submitted ICF/SIS materials for participating Member States.

Geography

Total Number Of Sites
67
Total Number Of Participants
350

Germany

Earliest CTIS Part Ii Submission Date
26-09-2024
Latest Decision Or Authorization Date
08-04-2026
Processing Time Days
559
Number Of Sites
61
Number Of Participants
320

Sites

Site Name
Universitaetsmedizin Goettingen
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Christof Kramm
Site Name
Gemeinschaftskrankenhaus Herdecke gGmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Alfred Laengler
Site Name
Universitaetsklinikum Muenster AöR
Department Name
Pediatric hematology/oncology
Contact Person Name
Birgit Froehlich
Site Name
Childrens Hospital Of Koblenz
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Rainer Misgeld
Contact Person Email
rainer.misgeld@gk.de
Site Name
HELIOS Klinikum Erfurt GmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Axel Sauerbrey
Site Name
Klinikum Kassel GmbH
Department Name
Pediatric hematology/oncology
Contact Person Name
Martina Rodehueser
Contact Person Email
martina.rodehueser@gnh.net
Site Name
Universitätsklinikum Frankfurt
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Konrad Bochennek
Contact Person Email
Kinderhaematologie@ukffm.de
Site Name
Rheinische Friedrich-Wilhelms-Universitaet Bonn
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Gabriele Calaminus
Contact Person Email
kho.studienbuero@ukbonn.de
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Nora Naumann-Bartsch
Contact Person Email
nora.naumann@uk-erlangen.de
Site Name
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Judith Lohse
Contact Person Email
ivonne.haase@ukdd.de
Site Name
Universitaetsklinikum Koeln AöR
Department Name
pediatric hematologie/Oncology
Contact Person Name
Thorsten Simon
Site Name
Universitätsmedizin Greifswald
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Torsten Ebeling
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Martin Ebinger
Site Name
SLK-Kliniken Heilbronn GmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Monika Streiter
Site Name
Justus-Liebig-Universitaet Giessen
Department Name
Pediatric hematology/oncology
Contact Person Name
Dieter Koerholz
Site Name
Medical Center - University Of Freiburg
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Alexander Puzik
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Beate Winkler
Contact Person Email
b.winkler@uke.de
Site Name
Gesundheit Nord gGmbH Klinikverbund Bremen
Department Name
pediatric hematologie/Oncology
Contact Person Name
Stefan Froehling
Site Name
Ludwig Maximilian University Of Munich
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Irene Schmid
Site Name
Staedtisches Klinikum Braunschweig gGmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Johanna Scheer-Preis
Contact Person Email
j.scheer-preiss@skbs.de
Site Name
Universitaetsklinikum Regensburg AöR
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Anja Troeger
Contact Person Email
Judith.reinberg@ukr.de
Site Name
HELIOS Kliniken Schwerin GmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Aram Prokop
Site Name
Universitaetsklinikum Essen AöR
Department Name
Pediatric hematology/oncology
Contact Person Name
Stefan Schoenberger
Contact Person Email
paedonko-studien@uk-essen.de
Site Name
Staedtisches Klinikum Karlsruhe gGmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Alfred Leipold
Site Name
University Of Luebeck
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Martin Demmert
Site Name
University Hospital Jena KöR
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Bernd Gruhn
Contact Person Email
Bernd.Gruhn@med.uni-jena.de
Site Name
Universitaet Leipzig
Department Name
Pediatric hematology/oncology
Contact Person Name
Lars Fischer
Site Name
Helios Klinikum Krefeld GmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Thomas Imschweiler
Site Name
Saarland University Hospital
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Marc Remke
Site Name
Center For Pediatric And Adolescent Medicine Of The Johannes Gutenberg University Mainz
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Joerg Faber
Site Name
Universitätsmedizin Rostock
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Carl-Friedrich Classen
Site Name
Universitaetsklinikum Magdeburg AöR
Department Name
Pediatric hematology/oncology
Contact Person Name
Antje Redlich
Contact Person Email
dokupho@med.ovgu.de
Site Name
Asklepios Klinik Sankt Augustin GmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Martin Irnich
Contact Person Email
onko.st.augustin@asklepios.com
Site Name
Universitaetsklinikum Schleswig-Holstein
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Simon Vieth
Site Name
Diakoneo Klinik Hallerwiese-Cnopfsche Kinderklinik
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Joerg Leyh
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Pediatric hematology/oncology
Contact Person Name
Theresa Thole-Kliesch
Contact Person Email
theresa.thole@charite.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Department of Gynaecology and Obstetrics
Contact Person Name
Fabinshy Thanarajah
Site Name
Universitaetsklinikum Duesseldorf AöR
Department Name
Gynecological Oncology
Contact Person Name
Tanja Fehm
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Stella Okouoyo
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
gynaecological oncology
Contact Person Name
Barbara Schmalfeldt
Contact Person Email
gynstudien@uke.de
Site Name
Hospital Munich Schwabing
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Irene Teichert von Luettichau
Site Name
Technical University Of Munich School Of Medicine
Department Name
Clinic and Polyclinic for Gynecology
Contact Person Name
Holger Bronger
Site Name
Evangelisches Klinikum Bethel gGmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Norbert Jorch
Contact Person Email
norbert.jorch@evkb.de
Site Name
Universitaetsklinikum Duesseldorf AöR
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Florian Babor
Site Name
Kaiserswerther Diakonie
Department Name
Gynecological Oncology
Contact Person Name
Saher Baransi
Site Name
Kliniken der Stadt Koeln gGmbH
Department Name
pediatric hematologie/Oncology
Contact Person Name
Stefan Balzer
Contact Person Email
BalzerSt@kliniken-koeln.de
Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Gerrit Weber
Contact Person Email
weber_g1@ukw.de
Site Name
Vestische Kinder- und Jugendklinik Datteln
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Thomas Wiesel
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
gynaecological oncology
Contact Person Name
Alexander Burges
Site Name
Universitaetsklinikum Aachen AöR
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Udo Kontny
Contact Person Email
Kinderonkodoku@ukaachen.de
Site Name
Johannes Wesling Klinikum Minden
Department Name
Pediatric hematology/oncology
Contact Person Name
Bernhard Erdlenbruch
Site Name
Universitaetsklinikum Mannheim GmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Matthias Duerken
Contact Person Email
matthias.duerken@umm.de
Site Name
Carl-Thiem-Klinikum Cottbus gGmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Georg Schwabe
Contact Person Email
g.schwabe@ctk.de
Site Name
HELIOS Klinikum Berlin-Buch GmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Patrick Hundsdoerfer
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Lisa Nonnenmacher
Contact Person Email
onko.kinder@uniklinik-ulm.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Gynecological Oncology
Contact Person Name
Jalid Sehouli
Contact Person Email
isil.yalcinkaya@charite.de
Site Name
Medizinische Hochschule Hannover
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Rebecca Schultze-Florey
Site Name
Universitaetsklinikum Augsburg
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Michael Fruehwald
Site Name
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
Department Name
Gynecological Oncology
Contact Person Name
Pauline Wimberger
Contact Person Email
studiensekretariat.gyn@ukdd.de
Site Name
Universtitätsklinikum Halle (Saale) AöR
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Caspar Kuehnoel
Contact Person Email
ped-studyoffice@uk-halle.de
Site Name
Klinikum Dortmund gGmbH
Department Name
Pediatric Hematology/Oncology
Contact Person Name
Dominik T. Schneider

Netherlands

Earliest CTIS Part Ii Submission Date
26-09-2024
Latest Decision Or Authorization Date
10-04-2026
Processing Time Days
561
Number Of Sites
1
Number Of Participants
10

Sites

Site Name
Prinses Maxima Centrum voor Kinderoncologie B.V.
Department Name
Solid Tumours
Contact Person Name
A.M.C. Mavinkurve-Groothuis

Austria

Earliest CTIS Part Ii Submission Date
26-09-2024
Latest Decision Or Authorization Date
13-04-2026
Processing Time Days
564
Number Of Sites
5
Number Of Participants
20

Sites

Site Name
Kepler Universitaetsklinikum GmbH
Department Name
Pädiatrische Hämatologie und Onkologie
Contact Person Name
Barbara Winkler
Site Name
St. Anna Kinderspital GmbH
Department Name
Pädiatrische Hämatologie und Onkologie
Contact Person Name
Gernot Engstler
Contact Person Email
Gernot.Engstler@stanna.at
Site Name
Gemeinnuetzige Salzburger Landeskliniken Betriebsgesellschaft mbH
Department Name
Pädiatrische Hämatologie und Onkologie
Contact Person Name
Neil Jones
Contact Person Email
n.jones@salk.at
Site Name
Medizinische Universitaet Innsbruck
Department Name
Pädiatrische Hämatologie und Onkologie
Contact Person Name
Roman Crazzolara
Contact Person Email
roman.crazzolara@i-med.ac.at
Site Name
Medical University Of Graz
Department Name
Pädiatrische Hämatologie und Onkologie
Contact Person Name
Martin Benesch

Sponsor

Primary sponsor

Full Name
Rheinische Friedrich-Wilhelms-Universitaet Bonn
Organisation Type
Educational Institution
Country Of Registered Address
Germany

Investigational products

Investigational Product Name
ETOPOSIDE
Active Substance
ETOPOSIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
2
Maximum Dose
300 mg/m2
Investigational Product Name
IFOSFAMIDE
Active Substance
IFOSFAMIDE
Modality
Small molecule
Routes Of Administration
INTRAVENIOUS INFUSION
Route
Intravenous
Authorisation Status
2
Maximum Dose
2000 mg/m2
Investigational Product Name
CISPLATIN
Active Substance
CISPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
2
Maximum Dose
20 mg/m2
Investigational Product Name
CARBOPLATIN
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
2
Maximum Dose
600 mg/m2
Combination Treatment
Yes

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