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Multicentre prospective trial for extracranial malignant germ cell tumours including a randomized comparison of Carboplatin and Cisplatin

Organizational Data

DRKS-ID:
DRKS00019921
Recruitment Status:
Recruiting ongoing
Date of registration in DRKS:
2019-11-19
Last update in DRKS:
2023-09-15
Registration type:
Prospective

Acronym/abbreviation of the study

MAKEI V

URL of the study

No Entry

Brief summary in lay language

MAKEI V aims to further improve the situation for patients with malignant germ cell tumors. Evaluations of previous studies have shown that certain criteria have an influence on the course of the disease and are important for risk assessment. These criteria include, for example, tumor localization, extension/metastasis, tissue type, and patient age. Thus a classification into defined risk groups is possible, which in turn define the type of treatment, so that a risk-adapted therapy can be carried out. Depending on the risk group, germ cell tumours are treated either by surgery alone or by a combination of surgery and chemotherapy. By comparing two chemotherapeutic agents (cisplatin and carboplatin), MAKEI V aims to check whether the use of carboplatin allows the same survival rates with lower therapy-related toxicity and fewer side effects as with the previous therapy with cisplatin.

Brief summary in scientific language

Prospective, multicentre phase III-trial in malignant extracranial germ cell tumours including a randomization between Carboplatin- and Cisplatin-combination standard chemotherapy (CTx) based on a risk-stratification derived from the preceding MAKEI 96 trial and published data. The treatment will be administered after risk stratification and within the specific risk groups, which are defined by tumour site, stage, age and resection status.

Health condition or problem studied

ICD10:
C80 - Malignant neoplasm, without specification of site
Healthy volunteers:
No Entry

Interventions, Observational Groups

Arm 1:
Each cycle of CarboPE consists of: Carboplatin 600 mg/m² Etoposid 300 mg/m² Each cycle of CarboPEI consists of: Carboplatin 600 mg/m² Etoposid 300 mg/m² Ifosfamid 7500 mg/m² Each cycle of Carbo-di-PEI consists of: Carboplatin 600 mg/m² Etoposid 1500 mg/m² Ifosfamid 10000 mg/m²
Arm 2:
Each cycle of PE consists of: Carboplatin 600 mg/m² Etoposid 300 mg/m² Each cycle of PEI consists of: Carboplatin 600 mg/m² Etoposid 300 mg/m² Ifosfamid 7500 mg/m² Each cycle of di-PEI consists of: Carboplatin 600 mg/m² Etoposid 1500 mg/m² Ifosfamid 10000 mg/m²

Endpoints

Primary outcome:
To assess in a randomized comparison whether the efficacy of Carboplatin (600 mg/m² per cycle / AUC 7.9 mg/ml/min.) is not inferior to Cisplatin (100 mg/m² per cycle) in malignant germ cell tumours (MGCT) of intermediate, high and very high risk with regard to Event-free-survival (EFSr). 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
Secondary outcome:
• 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 abnormalitie, 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

Study Design

Purpose:
Treatment
Allocation:
Randomized controlled study
Control:
  • Active control (effective treatment of control group)
Phase:
III
Study type:
Interventional
Mechanism of allocation concealment:
No Entry
Blinding:
No
Assignment:
Factorial
Sequence generation:
No Entry
Who is blinded:
No Entry

Recruitment

Recruitment Status:
Recruiting ongoing
Reason if recruiting stopped or withdrawn:
No Entry

Recruitment Locations

Recruitment countries:
  • Austria
  • Germany
  • Netherlands
  • Switzerland
Number of study centers:
Multicenter study
Recruitment location(s):
  • Medical center Helios Klinikum Krefeld Krefeld
  • University medical center Universitäts-Kinderklinik Würzburg
  • University medical center Universitätsklinik für Kinder- und Jugendmedizin Greifswald
  • Medical center Helios Klinikum Krefeld Krefeld
  • University medical center Universitäts-Kinderklinik Würzburg
  • University medical center Universitätsklinik für Kinder- und Jugendmedizin Greifswald
  • Medical center Evangelisches Krankenhaus Bielefeld gGmbH Bielefeld
  • University medical center Klinik für Kinder- u. Jugendmedizin Aachen
  • Medical center Asklepios Klinik Sankt Augustin St. Augustin
  • Medical center Cnopf'sche Kinderklinik Nürnberg
  • Medical center Kinderkrankenhaus Riehl Köln
  • University medical center Päd. Hämatologie / Onkologie Gießen
  • University medical center Zentrum für Kinder- und Jugendmedizin Frankfurt a.M.
  • University medical center Kinderklinik - Päd. Hämatologie/Onkologie Bonn
  • University medical center Zentrum für Geburtshilfe, Kinder- und Jugendmedizin Hamburg
  • University medical center Klinik für Kinder- und Jugendmedizin Jena
  • Medical center Klinikum Kassel GmbH, Pädiatrische Hämatologie und Onkologie Kassel
  • Medical center Helios Klinikum Berlin-Buch, Klinik für Kinder- und Jugendmedizin Berlin
  • Medical center Klinik für Kinder und Jugendliche Augsburg
  • University medical center Klinik für Kinder- und Jugendmedizin I Kiel
  • Medical center Johannes Wesling Klinikum Minden Minden
  • University medical center Kinder- und Jugendklinik Erlangen
  • University medical center Kinder- und Jugendklinik Rostock
  • University medical center Klinikum rechts der Isar: Frauenklinik München
  • Medical center Städtisches Klinikum Karlsruhe Karlsruhe
  • University medical center Klinik für Kinder- und Jugendmedizin Mannheim
  • University medical center Klinik für Kinder- und Jugendmedizin Ulm
  • University medical center Pädiatrische Hämatologie und Onkologie Münster
  • University medical center Klinik und Poliklinik für Gynäkologie Hamburg
  • Medical center Vestische Kinder- und Jugendklinik Datteln Datteln
  • University medical center Zentrum für Kinder- und Jugendmedizin Mainz
  • University medical center Pädiatrie I / Päd. Onkologie und Hämatologie Göttingen
  • Medical center Städtisches Klinikum Braunschweig gGmbH Braunschweig
  • Medical center Helios Klinikum Erfurt Erfurt
  • Medical center Kliniken Essen Mitte Evang. Huyssens-Stiftung Essen
  • University medical center Kinderheilkunde I Tübingen
  • University medical center Päd. Hämatologie und Onkologie Hannover
  • University medical center Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe Dresden
  • Medical center Klinikum Stuttgart - Olgahospital Stuttgart
  • Medical center Klinikum Oldenburg gGmbH Oldenburg
  • University medical center Zentrum für Kinder- und Jugendmedizin Freiburg
  • University medical center Zentrum für Kinder- und Jugendmedizin Essen
  • Medical center SLK Kliniken Heilbronn GmbH Heilbronn
  • University medical center Klinik für Frauenheilkunde und Geburtshilfe Essen
  • University medical center Charité - Klinik f. Pädiatrie m.S. Hämat./Onkologie Berlin
  • Medical center Klinikum Bremen Mitte Bremen
  • University medical center Klinik für Kinder- und Jugendmedizin Lübeck
  • University medical center Klinik und Poliklinik für Kinder- und Jugendmedizin Dresden
  • University medical center Poliklinik für Kinder und Jugendmedizin Halle Saale
  • Medical center Westfälisches Kinderzentrum Klinikum Dortmund
  • University medical center Charité - Klinik für Gynäkologie Berlin
  • Medical center Gemeinschaftskrankenhaus Herdecke Herdecke
  • University medical center Zentrum für Kinder‐ und Jugendmedizin Heidelberg
  • University medical center Päd. Hämatologie und Onkologie Magdeburg
  • University medical center Klinik und Poliklinik für Kinder‐ und Jugendmedizin Leipzig
  • Medical center Medizinische Hochschule Hannover Hannover
  • Medical center Kliniken der Stadt Köln gGmbH Köln
  • Medical center Helios Kliniken Schwerin GmbH Schwerin
  • Medical center GK Mittelrhein gGmbh Koblenz
  • University medical center Abteilung für Päd. Hämatologie und Onkologie und Stammzellentransplantation Regensburg

Recruitment period and number of participants

Planned study start date:
2019-11-26
Actual study start date:
2019-12-03
Planned study completion date:
No Entry
Actual Study Completion Date:
No Entry
Target Sample Size:
360
Final Sample Size:
No Entry

Inclusion Criteria

Sex:
All
Minimum Age:
no minimum age
Maximum Age:
29 Years
Additional 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

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. Note: Patients excluded from the trial based on the presence of exclusion criteria may be eligible for registration as follow-up patients. They shall receive adequate treatment and will not be evaluated for primary and secondary objectives. 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)

Addresses

Primary Sponsor

Medizinische Fakultät der Universität Bonn Rheinische Friedrich-Wilhelms Universität Bonn
Prof. Dr. Bernd Weber
Venusberg-Campus 1
53127 Bonn
Germany
Telephone:
No Entry
Fax:
No Entry
Contact per E-Mail
URL:
No Entry
Investigator Sponsored/Initiated Trial (IST/IIT):
Yes

Contact for Scientific Queries

Universitätsklinikum Bonn Zentrum für Kinder- und Jugendmedizin Abt. Päd. Hämatologie/Onkologie
Dr. Gabriele Calaminus
Adenauerallee119
53113 Bonn
Germany
Telephone:
0228-287-33389
Fax:
No Entry
Contact per E-Mail
URL:
No Entry

Contact for Public Queries

Universitätsklinikum Bonn Zentrum für Kinder- und Jugendmedizin Abt. Päd. Hämatologie/Onkologie
Dr. Gabriele Calaminus
Adenauerallee119
53113 Bonn
Germany
Telephone:
0228-287-33389
Fax:
No Entry
Contact per E-Mail
URL:
No Entry

Principal Investigator

Universitätsklinikum Bonn Zentrum für Kinder- und Jugendmedizin Abt. Päd. Hämatologie/Onkologie
Dr. Gabriele Calaminus
Adenauerallee119
53113 Bonn
Germany
Telephone:
0228-287-33389
Fax:
No Entry
Contact per E-Mail
URL:
No Entry

Sources of Monetary or Material Support

Private sponsorship (foundations, study societies, etc.)

Deutsche Krebshilfe
Buschstr. 32
53113 Bonn
Germany
Telephone:
02 28/7 29 90-0
Fax:
No Entry
Contact per E-Mail
URL:
http://www.krebshilfe.de

Ethics Committee

Address Ethics Committee

Ethik-Kommission Medizinische Fakultät Bonn
Venusberg Campus 1, Geb. 02
53105 Bonn
Germany
Telephone:
+49-228-28751282
Fax:
+49-228-28751932
Contact per E-Mail
URL:
No Entry

Vote of leading Ethics Committee

Date of ethics committee application:
2019-04-03
Ethics committee number:
140/19-AMG-ff
Vote of the Ethics Committee:
Approved
Date of the vote:
2019-08-12

Further identification numbers

Other primary registry ID:
No Entry
EudraCT Number:
2016-001784-36
UTN (Universal Trial Number):
No Entry
EUDAMED Number:
No Entry

IPD - Individual Participant Data

Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
Yes
IPD Sharing Plan:
On request to the sponsor.

Study protocol and other study documents

Study protocols:
No Entry
Study abstract:
No Entry
Other study documents:
No Entry
Background literature:
No Entry
Related DRKS studies:
No Entry

Publication of study results

Planned publication:
No Entry
Publikationen/Studienergebnisse:
No Entry
Date of first publication of study results:
No Entry
DRKS entry published for the first time with results:
No Entry

Basic reporting

Basic Reporting / Results tables:
No Entry
Brief summary of results:
No Entry