Clinical trial • Phase I • Oncology
VINCRISTINE SULFATE for Neuroblastoma
Phase I trial of VINCRISTINE SULFATE for Neuroblastoma. None/Not specified-controlled, adaptive. 39 participants.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Neuroblastoma
- Trial Stage
- Phase I
- Drug Modality
- Small molecule|Monoclonal antibody|Peptide/protein/enzyme
- Paediatric Trial
- Yes
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 01-03-2024
- First CTIS Authorization Date
- 22-06-2024
Trial design
None/Not specified-controlled, adaptive Phase I trial in Netherlands, France, Germany and others.
- Comparator
- None/Not specified
- Adaptive
- True, dose-escalation design to identify RP2D and MTD with DLT evaluation windows specified (GPOH: DLT evaluation cycles first N6 and second N5; rapid COJEC: first C and second B and A cycles). Interim safety-driven dose-escalation decisions implied though specific stopping/rule details are not provided in the available text.
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 39
Eligibility
Recruits 39 paediatric patients.
- Pregnancy Exclusion
- Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1
- Vulnerable Population
- Includes minors (patients aged ≥18 months and <18 years). Written informed consent required from parents/legal representative and from the patient, plus age-appropriate assent prior to any study-specific screening procedures, in accordance with local, regional or national law and legislation.
Inclusion criteria
- {"criterion_text":"- Established diagnosis of neuroblastoma Stage M, according to the SIOPEN modified International Neuroblastoma Risk Group (INRG) and to the INSS criteria"}
- {"criterion_text":"- Age ≥18 months and <18 years"}
- {"criterion_text":"- Body weight >12 kg."}
- {"criterion_text":"- Alanine transaminase (ALT) and aspartate aminotransferase (AST) <10 × upper limit of normal (ULN), total bilirubin <1.5 × ULN based on age specific reference ranges"}
- {"criterion_text":"- Calculated glomerular filtration rate (based on Schwartz formula; section 10.4.7) >60 mL/min/1.73 m2 or serum creatinine <1.5 × ULN corrected for age."}
- {"criterion_text":"- Shortening fraction (SF) ≥27% and/or left ventricular ejection fraction (LVEF) >50% as determined by echocardiography or MUGA."}
- {"criterion_text":"- Able to comply with scheduled follow-up and study procedures."}
- {"criterion_text":"- Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national law and legislation."}
Exclusion criteria
- {"criterion_text":"- Previous cancer-specific treatment for neuroblastoma"}
- {"criterion_text":"- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including conventional chemotherapeutics and dinutuximab beta."}
- {"criterion_text":"- Current use of a prohibited medication or requires any of these medications during the study (See Section 8.1.2 for details): a. Treatment with corticosteroids is not allowed within 2 weeks prior to the first treatment course and until 1 week after the last treatment course with dinutuximab beta, except for life-threatening conditions. b. Vaccinations (including seasonal influenza) are not allowed during administration of dinutuximab beta and until 10 weeks after last treatment course. c. Concomitant use of intravenous (IV) immunoglobulins is not allowed. d. Concomitant use of cardioprotectant dexrazoxane is not allowed."}
- {"criterion_text":"- Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1"}
- {"criterion_text":"- Breast feeding"}
- {"criterion_text":"- Sexually active participants not willing to use highly effective contraceptive method (pearl index <1) as defined in CTFG HMA 2020 (Appendix 2) during trial participation and until 6 months after end of protocol therapy"}
- {"criterion_text":"- Major surgery within 21 days prior to enrollment of the first treatment dose (open tumor biopsy or central line placement is not considered major surgery)."}
- {"criterion_text":"- History or documented evidence of severe acute or chronic infection or infectious illness requiring parenteral therapy unless fully healed (Grade <1) at least 4 weeks prior to start of treatment"}
- {"criterion_text":"- Patients with spinal cord involvement (symptomatic patients or if identified on imaging done to establish the diagnosis; there is no screening for spinal cord involvement for all patients)."}
- {"criterion_text":"- Patients with pre-existing grade 3-4 neurological toxicity."}
- {"criterion_text":"- Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Incidence of dose limiting toxicities (DLTs) associated with the combination of dinutuximab beta with GPOH (2 DLT evaluation cycles: first N6 and second N5 cycles) or rapid COJEC (first C and second B and A cycles) induction chemotherapy regimens.","definition_or_measurement_approach":"DLTs incidence assessed during specified DLT evaluation cycles: for GPOH regimen first N6 and second N5 cycles; for rapid COJEC first C and second B and A cycles."}
Secondary endpoints
- {"endpoint_text":"- Type, incidence, severity, seriousness and relationship to study medications for Grade 3 and 4 AEs, including laboratory abnormalities and severe adverse events (SAEs). • Cumulative incidence of treatment-related mortality and of disease-related mortality.","definition_or_measurement_approach":"Assessment of Grade 3 and 4 adverse events (including laboratory abnormalities and SAEs); cumulative incidence metrics for treatment-related and disease-related mortality."}
- {"endpoint_text":"- Overall response during and after induction (primary tumor, metastases).","definition_or_measurement_approach":"Overall response evaluated for primary tumour and metastases during induction and at end of induction (methods not further specified here)."}
- {"endpoint_text":"- mCR after induction treatment. mPR according to eligibility criteria to proceed to consolidation by HDC/ASCT: mPR for bone disease: MIBG uptake (or FDG-PET uptake for MIBG-non avid tumors) completely resolved or SIOPEN score ≤3 and at least 50% reduction in MIBG score (or ≤3 bone lesions and at least 50% reduction in number of FDG-PET-avid bone lesions for MIBG-non avid tumors). mPR for bone marrow disease: CR and/or MD according to INRC. mPR for other metastatic sites","definition_or_measurement_approach":"Definitions provided: mPR for bone disease based on MIBG/FDG-PET resolution or SIOPEN score ≤3 and ≥50% MIBG score reduction (or ≤3 bone lesions + ≥50% reduction in FDG-PET-avid lesions for MIBG-non avid tumors); mPR for bone marrow: CR and/or MD per INRC; mCR after induction measured per these response criteria."}
Recruitment
- Planned Sample Size
- 39
- Recruitment Window Months
- 72
- Consent Approach
- Written informed consent required from parents/legal representative and from the patient, plus age-appropriate assent, prior to any study-specific screening procedures, conducted according to local, regional or national law and legislation. No specific languages or age-specific document details provided in the record.
Geography
- Total Number Of Sites
- 13
- Total Number Of Participants
- 39
Netherlands
- Earliest CTIS Part Ii Submission Date
- 03-06-2024
- Latest Decision Or Authorization Date
- 22-06-2024
- Processing Time Days
- 19
- Number Of Sites
- 1
- Number Of Participants
- 8
Sites
- Site Name
- Prinses Maxima Centrum voor Kinderoncologie B.V.
- Department Name
- Specialisten SO
- Contact Person Name
- Miranda Dierselhuis
- Contact Person Email
- m.p.dierselhuis@prinsesmaximacentrum.nl
- Number Of Participants
- 8
France
- Earliest CTIS Part Ii Submission Date
- 01-04-2025
- Latest Decision Or Authorization Date
- 10-04-2025
- Processing Time Days
- 9
- Number Of Sites
- 3
- Number Of Participants
- 10
Sites
- Site Name
- Hopital de la Timone Enfants
- Department Name
- Pediatric oncology
- Contact Person Name
- Gabriel Revon-Riviere
- Contact Person Email
- Gabriel.revon-riviere@ap-hm.fr
- Site Name
- Institut Gustave Roussy
- Department Name
- Children and adolescent oncology
- Contact Person Name
- Pablo Berlanga
- Contact Person Email
- pablo.berlanga@gustaveroussy.fr
- Site Name
- Centre Oscar Lambret
- Department Name
- Pediatric unit - Oncology
- Contact Person Name
- Anne-Sophie Defachelles
- Contact Person Email
- as-defachelles@o-lambret.fr
Germany
- Earliest CTIS Part Ii Submission Date
- 17-03-2025
- Latest Decision Or Authorization Date
- 10-04-2025
- Processing Time Days
- 24
- Number Of Sites
- 3
- Number Of Participants
- 10
Sites
- Site Name
- Universitaetsmedizin Greifswald KöR
- Department Name
- Department of Pediatrics, Pediatric Hematology and Oncology/BMT
- Contact Person Name
- Holger Lode
- Contact Person Email
- holger.lode@med.uni-greifswald.de
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Klinik für Pädiatrie m.S. Onkologie und Hämatologie
- Contact Person Name
- Hedwig Deubzer
- Contact Person Email
- hedwig.deubzer@charite.de
- Site Name
- University Of Cologne
- Department Name
- Department of Pediatric Oncology and Hematology
- Contact Person Name
- Thorsten Simon
- Contact Person Email
- thorsten.simon@uk-koeln.de
Spain
- Earliest CTIS Part Ii Submission Date
- 06-02-2025
- Latest Decision Or Authorization Date
- 21-03-2025
- Processing Time Days
- 43
- Number Of Sites
- 2
- Number Of Participants
- 8
Sites
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- Oncologia Pediatrica
- Contact Person Name
- Maria Adela Cañete Nieto
- Contact Person Email
- canyete_ade@gva.es
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Oncologia Pediatrica
- Contact Person Name
- Lucas Moreno Martin Retortillo
- Contact Person Email
- lucas.moreno@vallhebron.cat
Austria
- Earliest CTIS Part Ii Submission Date
- 23-06-2025
- Latest Decision Or Authorization Date
- 14-07-2025
- Processing Time Days
- 21
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- St. Anna Kinderspital GmbH
- Department Name
- Hemato-Oncology Station 2B
- Contact Person Name
- Heidrun Boztug
- Contact Person Email
- heidrun.boztug@stanna.at
Italy
- Earliest CTIS Part Ii Submission Date
- 20-06-2025
- Latest Decision Or Authorization Date
- 10-07-2025
- Processing Time Days
- 20
- Number Of Sites
- 2
- Number Of Participants
- 1
Sites
- Site Name
- IRCCS Istituto Giannina Gaslini
- Department Name
- UOC Oncologia
- Contact Person Name
- Carla Manzitti
- Contact Person Email
- carlamanzitti@gaslini.org
- Site Name
- Ospedale Pediatrico Bambino Gesu
- Department Name
- UOC Oncoematologia, Trapianto Emopoietico, Terapie Cellulari e Trial
- Contact Person Name
- Franco Locatelli
- Contact Person Email
- franco.locatelli@opbg.net
Poland
- Earliest CTIS Part Ii Submission Date
- 05-06-2025
- Latest Decision Or Authorization Date
- 14-07-2025
- Processing Time Days
- 39
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Uniwersytecki Szpital Dzieciecy W Krakowie
- Department Name
- Pediatric Oncology and Hematology Department
- Contact Person Name
- Aleksandra Wieczorek
- Contact Person Email
- sekhem@usdk.pl
Sponsor
Primary sponsor
- Full Name
- Prinses Maxima Centrum voor Kinderoncologie B.V.
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- Netherlands
Third parties
- {"country":"","full_name":"EUSA Pharma","duties_or_roles":"Source of monetary support","organisation_type":""}
Investigational products
- Investigational Product Name
- Vincristine Sulfate 1 mg/ml Solution for Injection or Infusion
- Active Substance
- VINCRISTINE SULFATE
- Modality
- Small molecule
- Routes Of Administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route
- Intravenous (as solution for infusion)
- Authorisation Status
- Marketing authorisation
- Investigational Product Name
- Cisplatin 1 mg/ml Concentrate for Solution for Infusion
- Active Substance
- CISPLATIN
- Modality
- Small molecule
- Routes Of Administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route
- Intravenous (as solution for infusion)
- Authorisation Status
- Marketing authorisation
- Investigational Product Name
- Doxorubicin Teva 2 mg/ml Concentrate for Solution for Infusion
- Active Substance
- DOXORUBICIN HYDROCHLORIDE
- Modality
- Small molecule
- Routes Of Administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route
- Intravenous (as solution for infusion)
- Authorisation Status
- Marketing authorisation
- Investigational Product Name
- Eldisine Powder for Solution for Injection 5.0 mg
- Modality
- Small molecule
- Routes Of Administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route
- Intravenous (as solution for infusion)
- Authorisation Status
- Marketing authorisation
- Investigational Product Name
- Carboplatin 10 mg/ml concentrate for solution for infusion
- Active Substance
- CARBOPLATIN
- Modality
- Small molecule
- Routes Of Administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route
- Intravenous (as solution for infusion)
- Authorisation Status
- Marketing authorisation
- Investigational Product Name
- Qarziba 4.5 mg/mL concentrate for solution for infusion
- Active Substance
- DINUTUXIMAB BETA
- Modality
- Monoclonal antibody
- Routes Of Administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route
- Intravenous (as solution for infusion)
- Authorisation Status
- Marketing authorisation
- Orphan Designation
- Yes
- Investigational Product Name
- Mitoxana 1 g Powder for Sterile Concentrate
- Active Substance
- IFOSFAMIDE
- Modality
- Small molecule
- Routes Of Administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route
- Intravenous (as solution for infusion)
- Authorisation Status
- Marketing authorisation
- Investigational Product Name
- Cyclophosphamide 1000 mg Powder for Solution for Injection or Infusion
- Active Substance
- CYCLOPHOSPHAMIDE
- Modality
- Small molecule
- Routes Of Administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route
- Intravenous (as solution for infusion)
- Authorisation Status
- Marketing authorisation
- Investigational Product Name
- Etoposide 20 mg/ml Concentrate for Solution for Infusion
- Active Substance
- ETOPOSIDE
- Modality
- Small molecule
- Routes Of Administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route
- Intravenous (as solution for infusion)
- Authorisation Status
- Marketing authorisation
- Investigational Product Name
- Dacarbazine Lipomed 200 mg powder for solution for injection or infusion
- Active Substance
- DACARBAZINE
- Modality
- Small molecule
- Routes Of Administration
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route
- Intravenous (as solution for infusion)
- Authorisation Status
- Marketing authorisation
- Combination Treatment
- Yes
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