Clinical trial • Phase III • Oncology

IFOSFAMIDE for Germ cell tumor (relapsed or refractory)

Phase III trial of IFOSFAMIDE for Germ cell tumor (relapsed or refractory).

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Germ cell tumor (relapsed or refractory)
Trial Stage
Phase III
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
05-08-2024
First CTIS Authorization Date
27-08-2024

Trial design

Randomised, randomized comparison of conventional-dose chemotherapy tip (paclitaxel + ifosfamide + cisplatin) versus high-dose chemotherapy ti-ce (mobilizing paclitaxel + ifosfamide followed by high-dose carboplatin and etoposide with autologous stem cell transplant). dose and schedule details not specified in the provided record.-controlled Phase III trial in Netherlands, Belgium, Denmark and others.

Randomised
Yes
Comparator
Randomized comparison of conventional-dose chemotherapy TIP (paclitaxel + ifosfamide + cisplatin) versus high-dose chemotherapy TI-CE (mobilizing paclitaxel + ifosfamide followed by high-dose carboplatin and etoposide with autologous stem cell transplant). Dose and schedule details not specified in the provided record.
Target Sample Size
219

Stratification factors

  • Modified IPFSG risk category

Eligibility

Recruits 219 paediatric patients.

Vulnerable Population
Written informed consent is required according to ICH/GCP and national/local regulations. Age-specific subject information and consent forms are provided (including forms for patients 14-15 years old, forms for patients 16-17, and forms for parents or legal representatives). Country-specific/local language ICFs and addenda are included in the dossier; assent/parental consent processes are supported by dedicated documents for minors.

Inclusion criteria

  • {"criterion_text":"- Confirmation of GCT histology (both seminoma and nonseminoma) on pathologic review at the center of enrollment. Tumor may have originated in any primary site.\n- Negative Serology (antibody test) for the following infectious diseases: a. Human Immunodeficiency Virus (HIV) type 1 and 2; b. Human T-cell Leukemia Virus (HTLV) type 1 and 2 (mandatory in US but optional in Canada and Europe); c. Hepatitis B surface antigen; d. Hepatitis C antibody\n- Reproductive risk: patient must not father a baby while in this study. The treatment could affect sperm or semen. Therefore, patient and his partner must use an appropriate and effective contraceptive method during the study period and for approximately 6 months after taking the last dose of study drug. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently.\n- Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.\n- Must have evidence of progressive or recurrent GCT (measurable or non-measurable) following one line of cisplatin-based chemotherapy, defined as meeting at least one of the following criteria: * Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT (enrollment on this study for adjuvant treatment after macroscopically complete resection of viable GCT is not allowed). In the event of an incomplete gross resection where viable GCT is found, patients will be considered eligible for the study. * Consecutive elevated serum tumor markers (HCG or AFP) that are increasing. Increase of an elevated LDH alone does not constitute progressive disease. * Development of new or enlarging lesions in the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to increase.\n- Must have received 3-6 cycles of cisplatin-based chemotherapy as part of first-line (initial) chemotherapy. Prior POMBACE, CBOP-BEP, or GAMEC are allowed.\n- No more than one prior line of chemotherapy for GCT (other than the 1 cycle of salvage chemotherapy).\n- Must have adequate recovery from prior surgery (e.g., healed scar, resumption of diet, etc.).\n- Age ≥ 14 years (≥ 15 years in France, ≥ 16 years in Ireland, ≥ 18 years in Germany, Denmark, Switzerland, the Netherlands, Slovenia and Italy)\n- ECOG Performance Status 0 to 2\n- Male gender\n- Required Initial Laboratory Values: Absolute Neutrophil Count (ANC) ≥ 1,500/mm3; Platelet Count ≥ 100,000/mm3; Calc. Creatinine Clearance ≥ 50 mL/min; Bilirubin ≤ 2.0 x upper limits of normal (ULN); AST/ALT ≤ 2.5 x upper limits of normal (ULN)"}

Exclusion criteria

  • {"criterion_text":"- Prior treatment with high-dose chemotherapy (defined as treatment utilizing stem cell rescue).\n- Contraindications to the use of paclitaxel, ifosfamide, cisplatine, carboplatine and etoposide as per summary of product characteristics (SPC).\n- Prior treatment with TIP with the exception when given as a bridge to treatment on protocol for patients with rapidly progressive disease who cannot wait to complete the eligibility screening process. Only one cycle is allowed.\n- Concurrent treatment with other cytotoxic drugs or targeted therapies.\n- Radiation therapy (other than to the brain) within 14 days of day 1 of protocol chemotherapy except radiation to brain metastases, which must be completed 7 days prior to start of chemotherapy.\n- Previous chemotherapy within 16 days prior to enrollment except for bleomycin which cannot have been given within 5 days prior to enrollment.\n- Concurrent malignancy other than non-melanoma skin cancer, superficial noninvasive (pTa or pTis) TCC of the bladder, contralateral GCT, or intratubular germ cell neoplasia. Patients with a prior malignancy, but at least 2 years since any evidence of disease are allowed.\n- Late relapse with completely surgically resectable disease. Patients with late relapses (defined as relapse ≥ 2 years from the date of completion of the last chemotherapy regimen) whose disease is completely surgically resectable are not eligible. Patients with late relapses who have unresectable disease are eligible.\n- Large (≥ 2 cm) hemorrhagic or symptomatic brain metastases until local treatment has been administered (radiation therapy or surgery). Treatment may begin ≥ 7 days after completion of local treatment. Patients with small (< 2 cm) and asymptomatic brain metastases are allowed and may be treated with radiation therapy and/or surgery concurrently with Arm A or cycles 1 and 2 of Arm B if deemed medically indicated. Radiation therapy should not be given concurrently with highdose carboplatin or etoposide.\n- Secondary somatic malignancy arising from teratoma (e.g., teratoma with malignant transformation) when it is actively part of the disease recurrence or progression."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Progression Free Survival (PFS)\n- Favorable Response Rate (FRR)\n- Treatment-related mortality\n- Toxicity","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
219
Recruitment Window Months
142
Consent Approach
Written informed consent is required prior to registration/randomization according to ICH/GCP and national/local regulations. Age-specific information and consent/assent forms are provided (adult forms; forms for patients aged 14-15; forms for patients aged 16-17; forms for parents or legal representatives). Country-specific/local language consent documents and addenda are included in the trial documents.

Geography

Total Number Of Sites
25
Total Number Of Participants
201

Netherlands

Earliest CTIS Part Ii Submission Date
20-08-2024
Latest Decision Or Authorization Date
27-08-2024
Processing Time Days
7
Number Of Sites
1
Number Of Participants
20

Sites

Site Name
Netherlands Cancer Institute
Department Name
Medical Oncology
Principal Investigator Name
Martijn Kerst
Principal Investigator Email
j.kerst@nki.nl
Contact Person Name
Martijn Kerst
Contact Person Email
j.kerst@nki.nl

Belgium

Earliest CTIS Part Ii Submission Date
20-08-2024
Latest Decision Or Authorization Date
28-08-2024
Processing Time Days
8
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Institut Jules Bordet
Department Name
Chemotherapy
Principal Investigator Name
Thierry Gil
Principal Investigator Email
thierry.gil@hubruxelles.be
Contact Person Name
Thierry Gil
Contact Person Email
thierry.gil@hubruxelles.be

Denmark

Earliest CTIS Part Ii Submission Date
20-08-2024
Latest Decision Or Authorization Date
30-08-2024
Processing Time Days
10
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Rigshospitalet
Department Name
Medical Oncology
Principal Investigator Name
Gedske Daugaard
Principal Investigator Email
kirsten.gedske.daugaard@regionh.dk
Contact Person Name
Gedske Daugaard

France

Earliest CTIS Part Ii Submission Date
20-08-2024
Latest Decision Or Authorization Date
03-09-2024
Processing Time Days
14
Number Of Sites
5
Number Of Participants
35

Sites

Site Name
Institut Gustave Roussy
Department Name
Hematology
Principal Investigator Name
Cristina Castilla Llorente
Contact Person Name
Cristina Castilla Llorente
Site Name
Centre Leon Berard
Department Name
Medical Oncology
Principal Investigator Name
Aude Flechon
Principal Investigator Email
aude.flechon@lyon.unicancer.fr
Contact Person Name
Aude Flechon
Contact Person Email
aude.flechon@lyon.unicancer.fr
Site Name
Oncopole Claudius Regaud
Department Name
Medical Oncology
Principal Investigator Name
Loic Mourey
Principal Investigator Email
mourey.loic@iuct-oncopole.fr
Contact Person Name
Loic Mourey
Contact Person Email
mourey.loic@iuct-oncopole.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Medical Oncology
Principal Investigator Name
Jean-Pierre Lotz
Principal Investigator Email
jean-pierre.lotz@tnn.aphp.fr
Contact Person Name
Jean-Pierre Lotz
Contact Person Email
jean-pierre.lotz@tnn.aphp.fr
Site Name
Institut Paoli Calmettes
Department Name
Medical Oncology
Principal Investigator Name
Gwenelle Gravis
Principal Investigator Email
gravisg@ipc.unicancer.fr
Contact Person Name
Gwenelle Gravis
Contact Person Email
gravisg@ipc.unicancer.fr

Germany

Earliest CTIS Part Ii Submission Date
20-08-2024
Latest Decision Or Authorization Date
27-08-2024
Processing Time Days
7
Number Of Sites
10
Number Of Participants
72

Sites

Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Medical Oncology
Principal Investigator Name
Sebastian Ochsenreither
Principal Investigator Email
sebastian.ochsenreither@charite.de
Contact Person Name
Sebastian Ochsenreither
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Medical Oncology
Principal Investigator Name
Carsten Bokemeyer
Principal Investigator Email
c.bokemeyer@uke.de
Contact Person Name
Carsten Bokemeyer
Contact Person Email
c.bokemeyer@uke.de
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Internal Medicine
Principal Investigator Name
Miriam Kull
Principal Investigator Email
miriam.kull@uniklinik-ulm.de
Contact Person Name
Miriam Kull
Contact Person Email
miriam.kull@uniklinik-ulm.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Medical Oncology
Principal Investigator Name
Viktor Gruenwald
Principal Investigator Email
Viktor.Gruenwald@uk-essen.de
Contact Person Name
Viktor Gruenwald
Contact Person Email
Viktor.Gruenwald@uk-essen.de
Site Name
Philipps-Universitaet Marburg
Department Name
Internal Medicine
Principal Investigator Name
Andreas Burchert
Principal Investigator Email
Andreas.Burchert@med.uni-marburg.de
Contact Person Name
Andreas Burchert
Site Name
Technische Universitaet Dresden
Department Name
Medical Oncology
Principal Investigator Name
Stephan Richter
Principal Investigator Email
stephan.richter@uniklinikum-dresden.de
Contact Person Name
Stephan Richter
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Medical Oncology
Principal Investigator Name
Stefanie Zschaebitz
Principal Investigator Email
Stefanie.Zschaebitz@med.uni-heidelberg.de
Contact Person Name
Stefanie Zschaebitz
Site Name
Klinikum Nuernberg
Department Name
Medical Oncology
Principal Investigator Name
Kerstin Schaefer-Eckart
Principal Investigator Email
schaefer@klinikum-nuernberg.de
Contact Person Name
Kerstin Schaefer-Eckart
Contact Person Email
schaefer@klinikum-nuernberg.de
Site Name
Universitaetsklinikum Duesseldorf AöR
Department Name
Internal Oncology
Principal Investigator Name
Guido Kobbe
Principal Investigator Email
kobbe@med.uni-duesseldorf.de
Contact Person Name
Guido Kobbe
Contact Person Email
kobbe@med.uni-duesseldorf.de
Site Name
Rotkreuzklinikum Muenchen gGmbH
Department Name
Oncology
Principal Investigator Name
Marcus Hentrich
Principal Investigator Email
Harry.Reisch@swmbrk.de
Contact Person Name
Marcus Hentrich
Contact Person Email
Harry.Reisch@swmbrk.de

Ireland

Earliest CTIS Part Ii Submission Date
20-08-2024
Latest Decision Or Authorization Date
27-08-2024
Processing Time Days
7
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
St James's Hospital
Department Name
Medical Oncology
Principal Investigator Name
Dearbhaile O'Donnell
Principal Investigator Email
dodonnell@stjames.ie
Contact Person Name
Dearbhaile O'Donnell
Contact Person Email
dodonnell@stjames.ie

Spain

Earliest CTIS Part Ii Submission Date
20-08-2024
Latest Decision Or Authorization Date
09-09-2024
Processing Time Days
20
Number Of Sites
4
Number Of Participants
16

Sites

Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Medical Oncology
Principal Investigator Name
Pablo Maroto
Principal Investigator Email
jmaroto@santpau.cat
Contact Person Name
Pablo Maroto
Contact Person Email
jmaroto@santpau.cat
Site Name
Institut Catala D'oncologia
Department Name
Medical Oncology
Principal Investigator Name
Xavier Garcia Del Muro
Principal Investigator Email
garciadelmuro@iconcologia.net
Contact Person Name
Xavier Garcia Del Muro
Contact Person Email
garciadelmuro@iconcologia.net
Site Name
Hospital Universitario 12 De Octubre
Department Name
Medical Oncology
Principal Investigator Name
Enrique Gonzalez Billalabeitia
Principal Investigator Email
enrique.gonzalezbilla@gmail.com
Contact Person Name
Enrique Gonzalez Billalabeitia
Site Name
Hospital General Universitario Morales Meseguer
Department Name
Medical Oncology
Principal Investigator Name
Marta Zafra Poves
Principal Investigator Email
martazafrap@gmail.com
Contact Person Name
Marta Zafra Poves
Contact Person Email
martazafrap@gmail.com

Italy

Earliest CTIS Part Ii Submission Date
20-08-2024
Latest Decision Or Authorization Date
04-09-2024
Processing Time Days
15
Number Of Sites
2
Number Of Participants
46

Sites

Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Medical Oncology
Principal Investigator Name
Massimo Di Nicola
Principal Investigator Email
massimo.dinicola@istitutotumori.mi.it
Contact Person Name
Massimo Di Nicola
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
Medical Oncology
Principal Investigator Name
Paolo Pedrazzoli
Principal Investigator Email
p.pedrazzoli@smatteo.pv.it
Contact Person Name
Paolo Pedrazzoli
Contact Person Email
p.pedrazzoli@smatteo.pv.it

Sponsor

Primary sponsor

Full Name
Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi
Organisation Type
Patient organisation/association
Country Of Registered Address
Belgium

Third parties

  • {"country":"Ireland","full_name":"Cancer Trials Ireland","duties_or_roles":"","organisation_type":"Patient organisation/association"}
  • {"country":"United States","full_name":"The Ohio State University","duties_or_roles":"Tumor genetic analysis, pharmacogenomics","organisation_type":"Educational Institution"}
  • {"country":"France","full_name":"Unicancer","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"Sample shipment, biobanking","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"OncoDrugConsult B.V.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Philipps-Universitaet Marburg","duties_or_roles":"","organisation_type":"Educational Institution"}
  • {"country":"Luxembourg","full_name":"Luxembourg Institute Of Health","duties_or_roles":"Biobanking","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
IFOSFAMIDE
Active Substance
IFOSFAMIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS USE
Authorisation Status
2
Maximum Dose
6000
Investigational Product Name
CARBOPLATIN
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS USE
Authorisation Status
2
Maximum Dose
3600
Investigational Product Name
CISPLATIN
Active Substance
CISPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS USE
Authorisation Status
2
Maximum Dose
400
Investigational Product Name
ETOPOSIDE
Active Substance
ETOPOSIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS USE
Authorisation Status
2
Maximum Dose
3600
Investigational Product Name
PACLITAXEL
Active Substance
PACLITAXEL
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS USE
Authorisation Status
2
Maximum Dose
1000
Combination Treatment
Yes

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