Brief description of trial (Data source: BASEC)
Bösartige Keimzelltumore treten meist in den Keimdrüsen, also Eierstöcken oder Hoden, auf, aber auch an anderen Orten des Körpers. Sie kommen in jeder Altersgruppe vor, vom Säuglings- bis ins junge Erwachsenenalter. Durch Operation und Chemotherapie konnten die Heilungschancen in den letzten Jahrzehnten drastisch verbessert werden. Diese Massnahmen sind jedoch nicht selten mit schweren Nebenwirkungen verbunden. Bei der Therapie von Keimzelltumoren kann die Therapie langfristige Folgen wie Schwerhörigkeit und Nierenschädigung nach sich ziehen. Angesichts der sehr guten Gesamtprognose bei bösartigen Keimzelltumoren ist die Qualität des Überlebens heute ein wichtiger Aspekt bei der Gestaltung der Behandlung geworden. Dementsprechend liegt zunehmend der Schwerpunkt auf der Verringerung der Behandlungslast bei gleichzeitiger Aufrechterhaltung der Wirksamkeit der Behandlung.
MAKEI V ist eine internationale Therapieoptimierungsstudie, welche bösartige, ausserhalb des Zentralnervensystems gelegene, Keimzelltumore bei Kindern und Jugendlichen sowie bei jungen erwachsenen Patientinnen untersucht. Ein Hauptziel der Studie liegt darin, die Wirksamkeit und Nebenwirkungen der zwei Substanzen Cisplatin und Carboplatin kontrolliert zu vergleichen.
Health conditions investigated(Data source: BASEC)
Bösartige, extrakranielle Keimzelltumore
Health conditions
(Data source: WHO)
Extracranial germ cell tumours of any malignant histology, primary site and stage;Therapeutic area: Diseases [C] - Cancer [C04]
Rare disease
(Data source: BASEC)
No
Intervention investigated (e.g. drug, therapy or campaign)
(Data source: BASEC)
Je nach Lokalisation und Ausbreitung der Erkrankung werden die Patientinnen und Patienten in verschiedene Risikogruppen eingeteilt. Die Bekämpfung der Keimzelltumoren erfolgt je nach Risikogruppe durch eine alleinige Operation oder durch eine Kombination von Operation und Chemotherapie:
• Niedriges Risiko: Operation
• Mittleres Risiko: Operation und 2 Kurse Chemotherapie
• Hohes Risiko: Operation und 4 Kurse Chemotherapie
• Höchstes Risiko: Operation und 4 Kurse Chemotherapie, davon 3 dosis-intensivierte Chemotherapie.
Falls die Patientinnen und Patienten mittels Chemotherapie behandelt werden, werden sie nach dem Zufallsprinzip in verschiedene Therapiegruppen eingeteilt (Randomisierung). Die zwei Therapiegruppen unterscheiden sich lediglich darin, ob die Substanz Carboplatin oder Cisplatin verabreicht wird. Beide Medikamente werden seit vielen Jahren erfolgreich zur Behandlung von Keimzelltumoren eingesetzt. Von Carboplatin weiss man, dass dies zu weniger Nebenwirkungen führt. Durch den kontrollierten Vergleich vom bisherigen Cisplatin mit Carboplatin im Rahmen der Studie kann untersucht werden, ob durch den Einsatz von Carboplatin gleich gute Überlebensraten mit geringeren therapiebedingten Nebenwirkungen erreicht werden.
Interventions
(Data source: WHO)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CISPLATIN
CAS Number: 15663-27-1
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: up to
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CARBOPLATIN
CAS Number: 41575-94-4
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: up to
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ETOPOSIDE
CAS Number: 33419-42-0
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: up to
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: IFOSFAMIDE
CAS Number: 3778-73-2
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: up to
Criteria for participation in trial
(Data source: BASEC)
• Alter bei Diagnose unter 18 Jahren (oder bei Patientinnen mit Eierstocktumoren unter 30 Jahren)
• Bestätigte Diagnose eines bösartigen, extrakraniellen Keimzelltumors
• Schriftliche Einwilligungsbestätigung zur Studienteilnahme
Exclusion criteria
(Data source: BASEC)
• Schwangerschaft oder Stillen
• HIV Positivität
• Impfung mit einem Lebendimpfstoff innerhalb zwei Wochen vor Beginn der Studienbehandlung
Inclusion/Exclusion Criteria
(Data source: WHO)
Inclusion criteria:
- 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
- Written informed consent prior to trial entry of parents and/or patient
- Diagnosis of a chemotherapy-naïve extracranial MGCT
- Karnofsky-Index of >70% or ECOG-Status 0-II
- Negative pregnancy test within 7 days prior to start of treatment for female patients of childbearing potential, in case of ß-HCG secreting MGCT pregnancy has to be excluded by appropriate methods
Note: Any patient who is of reproductive age should agree to use adequate contraception for the duration of the trial treatment and until at least 12 months after end of therapy.
Are the trial subjects under 18? yes
Number of subjects for this age range: 300
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Exclusion criteria:
Exclusion criteria in general:
- Pregnancy
- Lactation
- Incomplete data at trial entry preventing risk group allocation
- HIV-positivity
- Live vaccine immunization within two weeks before start of protocol treatment
- Sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 12 months after end of chemotherapy
- 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.
- Any other medical, psychiatric or drug related condition, or social condition incompatible with protocol treatment.
Exclusion criteria in special indication:
- Second malignancies
- Negative preoperative tumour markers AFP and ß-HCG and solely pure teratoma histology
- Known hypersensitivity against Cisplatin, Carboplatin, Etoposide, Ifosfamide or other ingredients of the medicinal product
- Hearing impairment Grade 3 and 4 (CTCAE Vers.4.03)
-
Further information on trial
Date trial registered
Apr 8, 2019
Incorporation of the first participant
Aug 12, 2019
Recruitment status
Authorised-recruitment may be ongoing or finished
Academic title
(Data source: WHO)
Multicentre prospective trial for extracranial malignant germ cell tumours including a randomized comparison of Carboplatin and Cisplatin - MAKEI V
Type of trial
(Data source: WHO)
Interventional clinical trial of medicinal product
Design of the trial
(Data source: WHO)
Controlled: yesRandomised: yesOpen: yesSingle blind: noDouble blind: noParallel group: yesCross over: noOther: noIf controlled, specify comparator, Other Medicinial Product: yesPlacebo: noOther: noNumber of treatment arms in the trial: 2
Phase
(Data source: WHO)
Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no
Primary end point
(Data source: WHO)
Main Objective: To assess in a randomized comparison whether the efficacy of Carboplatin is not inferior to Cisplatin in malignant germ cell tumours (MGCT) of intermediate, high and very high risk with regard to Event-free-survival (EFSr);Secondary Objective: 1. Evaluation of EFS/OS rates in the defined risk-groups compared to results of MAKEI 96 and published data
2. Evaluation of toxicity in randomized patients in respect to numbers of days in hospital, numbers of applied platelet and red blood cell transfusions
3. Evaluation of ototoxicity, nephrotoxicity, cardiotoxicity and fertility relevant endocrine outcomes under and after treatment chemotherapy
4. Evaluation of patient-reported-outcomes
5. Implementation of standardized documentation of surgical procedures and evaluation of potential impact of variations in procedures on EFS
6. Evaluation of risk stratification for therapy implemented in MAKEI V based on standardized staging and pathological evaluation in comparison to MAKEI 96
7. Evaluation of radiological response after two or four cycles of chemotherapy
8. Evaluation of standard tumour marker kinetics after every cycle of chemotherapy
;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: Any timepoint from the date of randomization to one of the defined events.
Secundary end point
(Data source: WHO)
Timepoint(s) of evaluation of this end point: Any timepoint from the date of randomization to one of the defined events or analysis.;Secondary end point(s): - 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
- 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
- Health economic parameter, e.g. hospitalization days during treatment, number of blood transfusions, in respect to treatment with Carboplatin or Cisplatin
- Short and late toxicities according to CTCAE v4.03
- Assessment of safety: Adverse events and laboratory abnormalities, CTCAE v4.03 grade, timing, seriousness and relatedness.
- Fertility relevant endocrine outcomes, e.g. Estrogen, AMH, LH, FSH, Inhibin B.
- Patient reported outcomes including HRQoL, fatigue, sexual function and fertility outcomes (in adult patients)
- Determination of risk for relapse in respect to used surgical intervention
- Radiological response rate after two (and if applicable four) cycles of either Carboplatin or Cisplatin chemotherapy
- Standard tumour marker levels after every cycle of either Carboplatin or Cisplatin chemotherapy
Contact information
(Data source: WHO)
Deutsche Krebshilfe
Trial results
(Data source: WHO)
Results summary
Multicentre prospective trial for extracranial malignant germ cell tumours including a randomized comparison of Carboplatin and Cisplatin
Link to the results in the primary register
no information available yet
Information on the availability of individual participant data
no information available yet
Trial sites
Trial sites in Switzerland
(Data source: BASEC)
Aarau, Basel, Bellinzona, Bern, Geneva, Lausanne, Luzern, St. Gallen, Zurich
Countries
(Data source: WHO)
Switzerland might not appear as site of trial if it has not yet been entered as such in the WHO primary registry.
Germany
Contact for further information on the trial
Details of contact in Switzerland
(Data source: BASEC)
KD Dr. med. Sabine Kroiss
+41 44 266 74 55
sabine.kroiss@kispi.uzh.ch
Contact for general information
(Data source: WHO)
Dr. Judith Schilling
Venusberg-Campus 1
Studienzentrale Studienzentrum Bonn (SZB)
004922828719037
studienzentrale-szb@ukbonn.de
Contact for scientific information
(Data source: WHO)
Dr. Judith Schilling
Venusberg-Campus 1
Studienzentrale Studienzentrum Bonn (SZB)
004922828719037
studienzentrale-szb@ukbonn.de
Authorisation by the ethics committee (Data source: BASEC)
Name of the authorising ethics committee (for multicentre studies only the lead committee)
Kantonale
Ethikkommission Zürich
Date of authorisation by the ethics committee
07.03.2023
Further trial identification numbers
Trial identification number of the ethics committee (BASEC-ID)
(Data source: BASEC)
2022-02264
Secondary ID (Data source: WHO)
PAED-201601
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