Comparison of Carboplatin and Cisplatin in patients with extracranial malignant germ cell tumours

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Aug 2019 → ongoing

Decision date (initial)

2024-10-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Deutsche Krebshilfe

External identifiers

EU CT number

2023-507582-25-00

EudraCT number

2016-001784-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

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)

Secondary objectives 8

1. Evaluation of EFS/OSrates in the defined risk-groups compared to results of MAKEI 96 and published data
2. Evaluation of toxicity under treatment with Carboplatin or Cisplatin in the randomized patients in respect to numbers of days in hospital, numbers of applied platelet and red blood cell transfusions
3. Evaluation of toxicity under and after treatment with Carboplatin or Cisplatin in the randomized patients with respect to ototoxicity, nephrotoxicity, cardiotoxicity and fertility relevant endocrine outcomes
4. Evaluation of patient-reported-outcomes (PROs) including Health related Quality of Life (HRQoL) and fatigue. In adult patients: sexual function and fertility outcome
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. Low risk MGCT: Evaluation of extended use of watch & wait strategy in localized disease, including testicular tumours pT2N0M0, pT3-4N0M0 and ovarian tumours FIGO IC1/IC2 (without vascular/lymphatic invasion for both sites). Evaluation of prognosis after organ sparing surgery in localized gonadal GCT. Intermediate risk MGCT: Evaluation of a reduction of chemotherapy cycles in testicular tumours pT1-T4N1M0 and in pT2-T4N0M0 (with vascular/lymphatic invasion). Very high risk MGCT: Evaluation of treatment intensification for non-gonadal metastatic MGCT >10 years, testicular tumours pTx T2-T4, Any T, M1b and ovarian tumours FIGO IV.
7. Evaluation of radiological response after two (and if applicable four) cycles of either Carboplatin or Cisplatin chemotherapy
8. Evaluation of standard tumour marker kinetics after every cycle of either Carboplatin or Cisplatin chemotherapy

Conditions and MedDRA coding

Malignant Extracranial Germ Cell Tumours (MGCT)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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
2. Diagnosis of a chemotherapy-naïve extracranial MGCT
3. Written informed consent of patients and/or their parents according to national law prior to trial entry
4. Karnofsky-Index of >70% or ECOG-Status 0-II
5. 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 9

1. Pregnancy
2. Lactation
3. Incomplete data at trial entry preventing risk group allocation
4. HIV-positivity (does not apply to low risk patients, but must be available before randomisation)
5. Live vaccine immunization within two weeks before start of protocol treatment
6. Sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 12 months after end of chemotherapy
7. 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.
8. Any other medical, psychiatric or drug related condition, or social condition incompatible with protocol treatment
9. Actual audiometry not available ( does not apply to low risk patients)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 10

1. 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
2. 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
3. Health economic parameter, e.g. hospitalization days during treatment, number of blood transfusions, in respect to treatment with Carboplatin or Cisplatin
4. Short and late toxicities according to CTCAE v5.0
5. Assessment of safety: Adverse events and laboratory abnormalitie, CTCAE v5.0 grade, timing, seriousness and relatedness.
6. Fertility relevant endocrine outcomes, e.g. Estrogen, AMH, LH, FSH, Inhibin B.
7. Patient reported outcomes including HRQoL, fatigue, sexual function and fertility outcomes (in adult patients)
8. Determination of risk for relapse in respect to used surgical intervention
9. Radiological response rate after two (and if applicable four) cycles of either Carboplatin or Cisplatin chemotherapy
10. Standard tumour marker levels after every cycle of either Carboplatin or Cisplatin chemotherapy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Sponsor organisation

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Address

Venusberg-Campus 1, Venusberg Venusberg

City

Bonn

Postcode

53127

Country

Germany

Scientific contact point

Organisation

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Contact name

Gabriele Calaminus

Public contact point

Organisation

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Contact name

Gabriele Calaminus

Locations

3 EU/EEA countries · 69 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications