This study has been transitioned to CTIS with ID 2023-507582-25-00 check the CTIS register for the current data. PRIMARY OBJECTIVESThe primary objective of MAKEI V is to assess in a randomized comparison whether the efficacy of Carboplatin (600 mg/…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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
Background summary
Malignant Germ Cell Tumours (MGCTs) are a heterogeneous disease group and may
affect children, adolescents and young adults. Depending on the age at
diagnosis, MGCT vary significantly with regard to their primary site,
histologic diagnosis, biologic profile and clinical response to treatment. With
the introduction of Cisplatin-based chemotherapy combinations in the 1970*s,
overall prognosis of MGCT has dramatically improved with survival rates of up
to 90% in children.
For decades cisplatin has thus been the leading agent in the treatment of MGCT.
However, cisplatin is associated with potentially severe and long-lasting
toxicity, which affects outcome with considerable consequences especially in
young patients. In view of the very good overall prognosis in MGCT today,
quality of survival has become a leading aspect in treatment design.
Accordingly the current focus is on reduction of treatment burden whilst
maintaining treatment efficacy. Carboplatin is known to present with a more
favourable acute and long-term toxicity profile in comparison to cisplatin.
Yet, there is no definitive proof that carboplatin is not inferior to cisplatin
with regard to efficacy in MGCT. Particularly in children with MGCT randomized
studies addressing this issue are entirely lacking.
The MAKEI V trial examines for the first time this question for children,
adolescents and female young adults suffering from MGCT within a randomized
setting. In MAKEI V, four risk groups are defined based on stratification
according to localization, stage, age and resection status. This risk
stratification is derived from the results of the preceding study MAKEI 96 and
published data. MAKEI V patients with intermediate, high and very high risk
will be randomized to receive either carboplatin or cisplatin-based
combination chemotherapy as the primary objective in a non-inferiority
statistical design with event-free survival as the primary end point. Outcome
in the low risk groups will be analysed within the secondary objectives.
Study objective
This study has been transitioned to CTIS with ID 2023-507582-25-00 check the CTIS register for the current data.
PRIMARY OBJECTIVES
The primary objective of MAKEI V is 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 GCT (MGCT) of
intermediate, high and very high risk with regard to Event-free survival (EFSr).
SECONDARY- AND EXPLORATIVE OBJECTIVES
- Evaluation of EFS/OS-rates in the defined risk-groups compared to results of
preceding consecutive trials (MAKEI 96) and published data.
- Evaluation of toxicity under treatment with Carbo- or Cisplatin patients in
respect to numbers of days in hospital and numbers of applied transfusions of
platelets and red blood cells
- Evaluation of toxicity during and after treatment with Carboplatin or
Cisplatin in randomized patients with respect to ototoxicity, nephrotoxicity,
cardiotoxicity and fertility relevant endocrine outcomes.
- Evaluation of patient-reported-outcomes (PROs) including HRQoL, fatigue,
sexual function and subjective fertility outcome (in adult patients)
- Implementation of standardized documentation of surgical procedures and
evaluation of potential impact of variations in procedures on EFS.
- Evaluation of risk stratification for therapy implemented in MAKEI V based on
standardized staging and pathological evaluation in comparison to MAKEI 96
- Evaluation of radiological response after two (and if applicable four) cycles
of either Carboplatin or Cisplatin chemotherapy.
- Evaluation of standard tumour marker kinetics after every cycle of either
Carboplatin or Cisplatin Chemotherapy
- Correlation of miRNA levels with standard tumour marker levels and outcome
- Establishment of a biomaterial bank for tumour tissue and blood samples to
support biological studies of MGCT.
Study design
Prospective, multicentre phase III-trial in malignant extracranial germ cell
tumours including a randomization between Carboplatin- and
Cisplatin-combination standard chemotherapy based on a risk-stratification
derived from the preceding MAKEI 96 trial and published data
Intervention
Randomised treatment of participants with intermediate, high, or very high risk
disease with standard cisplatin (100 mg/m2 per cycle) or carboplatin (600 mg/m2
per cycle)
Study burden and risks
This protocol treatment with the cisplatin is also the standard treatment for
patients with this disease. All modifications are intended to show that
Cisplatin can be exchanged for Carboplatin aiming to reduce treatment burden
and decrease treatment related side effects without influence on the outcome.
Parents and participants are asked to fill in questionnaires at 4 time points.
This takes about 20-30 minutes each time. The burden of blood sampling is
negligible compared to standard care.
The potential risks of MAKEI V are:
- the possibility that Carboplatin is inferior to Cisplatin with regard to EFS
in the randomized risk groups.
- that the toxicity profile of Carboplatin displays higher myelotoxicity in
comparison to Cisplatin with the need for blood transfusions harboring risks of
transmitting infections and leading to prolongation of hospital visit.
- that the treatment intensification for very high risk patients leads to a
higher rate of death of complications
Venusberg-campus 1
Bonn 53127
DE
Venusberg-campus 1
Bonn 53127
DE
Listed location countries
Age
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.
- Diagnosis of a chemotherapy-naïve extracranial MGCT
- Written informed consent of patients and/or their parents according to
national law prior to trial entry
- Karnofsky-Index of >70% or ECOG-Status 0-II
- 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
- 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
- Any other medical, psychiatric or drug related condition, or social condition
incompatible with protocol treatment.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-507582-25-00 |
| Other | DRKS00019921 |
| EudraCT | EUCTR2016-001784-36-NL |
| CCMO | NL81795.041.22 |