Trial document



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  DRKS00019921

Trial Description

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Title

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

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Trial Acronym

MAKEI V

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URL of the Trial

[---]*

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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.

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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.

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Do you plan to share individual participant data with other researchers?

Yes

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Description IPD sharing plan:

On request to the sponsor.

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Organizational Data

  •   DRKS00019921
  •   2019/11/19
  •   [---]*
  •   yes
  •   Approved
  •   140/19-AMG-ff, Ethik-Kommission der Medizinischen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn
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Secondary IDs

  •   2016-001784-36 
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Health Condition or Problem studied

  •   C80 -  Malignant neoplasm, without specification of site
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Interventions/Observational Groups

  •   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
  •   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
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Factorial
  •   III
  •   No
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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

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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

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
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Recruitment

  •   Actual
  •   2019/12/03
  •   360
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   no minimum age
  •   29   Years
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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

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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)

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Addresses

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    • Medizinische Fakultät der Universität Bonn Rheinische Friedrich-Wilhelms Universität Bonn
    • Mr.  Prof. Dr.  Bernd  Weber 
    • Venusberg-Campus 1
    • 53127  Bonn
    • Germany
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    • Universitätsklinikum Bonn Zentrum für Kinder- und Jugendmedizin Abt. Päd. Hämatologie/Onkologie
    • Ms.  Dr.  Gabriele  Calaminus 
    • Adenauerallee119
    • 53113  Bonn
    • Germany
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    • Universitätsklinikum Bonn Zentrum für Kinder- und Jugendmedizin Abt. Päd. Hämatologie/Onkologie
    • Ms.  Dr.  Gabriele  Calaminus 
    • Adenauerallee119
    • 53113  Bonn
    • Germany
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Sources of Monetary or Material Support

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    • Deutsche Krebshilfe
    • Gerd  Nettekoven 
    • Buschstr. 32
    • 53113  Bonn
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.