Clinical trial • Phase II • Oncology

nimotuzumab for Diffuse intrinsic pontine glioma | Brain stem glioma

Phase II trial of nimotuzumab for Diffuse intrinsic pontine glioma | Brain stem glioma.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Diffuse intrinsic pontine glioma | Brain stem glioma
Trial Stage
Phase II
Drug Modality
Monoclonal antibody | Small molecule
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
29-04-2024
First CTIS Authorization Date
26-06-2024

Trial design

Randomised, open-label, two randomized arms: (1) conventional (standard) radiotherapy with concomitant nimotuzumab and vinorelbine; (2) experimental irradiation approach (re-irradiation at relapse / multiple elective radiotherapy courses) with concomitant vinorelbine and nimotuzumab. doses specified in product information: nimotuzumab maximum 150 mg/m2, navelbine (vinorelbine tartrate) maximum 25 mg/m2; specific schedules not stated in the record.-controlled Phase II trial across 5 sites in Italy.

Randomised
Yes
Open Label
Yes
Comparator
Two randomized arms: (1) conventional (standard) radiotherapy with concomitant nimotuzumab and vinorelbine; (2) experimental irradiation approach (re-irradiation at relapse / multiple elective radiotherapy courses) with concomitant vinorelbine and nimotuzumab. Doses specified in product information: NIMOTUZUMAB maximum 150 mg/m2, NAVELBINE (vinorelbine tartrate) maximum 25 mg/m2; specific schedules not stated in the record.
Target Sample Size
81
Trial Duration For Participant
252

Eligibility

Recruits 81 paediatric patients.

Pregnancy Exclusion
Organ dysfunction, pregnancy or breast-feeding
Vulnerable Population
Trial includes pediatric participants aged 2 to 21; isVulnerablePopulationSelected is true. Written and signed informed consent from parents or legal guardians will be obtained before starting the treatment. No specific mention of patient assent processes or age-specific consent documents or available languages.

Inclusion criteria

  • {"criterion_text":"- Patients from 2 to 21 years old will be eligible\n- No previous treatment consented apart from steroids\n- Strict eligibility criteria will radiologically-verified DIPG (an intrinsic, pontine-based infiltrative lesion hypointense on T1- and hyperintense on T2-weighted sequences, involving at least 2/3 of the pons) [Hargrave]\n- Symptoms lasting less than 6 months, life expectancy ≥4 weeks; Karnowski/Lansky performance status ≥ 40 %\n- No organ dysfunction; no pregnancy or breast-feeding\n- Patients undergo baseline cranial MRI with gadolinium, to be repeated if treatment begins more than 2 weeks; spinal MRI due to the occurrence of metastatic cases at diagnosis will also be mandatory\n- Written and signed informed consent from parents or legal guardians will be obtained before starting the treatment\n- For diffuse midline glioma observational arm, central reviewed pathology of the disease according to standard Italian procedure, i.e. referral to the Neuropathology at Sapienza University in Rome"}

Exclusion criteria

  • {"criterion_text":"- Patients below 2 years or over 21\n- Pre-treatment with radio or chemotherapy\n- Neurofibromatosis 1\n- Non-typical imaging\n- Symptoms duration over 6 months, Lansky/Karnowski scores below 40%\n- Metastatic disease as shown by MRI\n- Organ dysfunction, pregnancy or breast-feeding\n- Absence of parents, patient or tutor consent\n- Not central review diagnosis of diffuse midline glioma histone H3, K27 mutated"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Number of best responses (complete and partial responses) up to week 36 will be calculated in the conventional and experimental irradiation arms, and the comparison between the response rates will be performed","definition_or_measurement_approach":"Number of best responses (complete and partial responses, CR+PR) up to 36 weeks will be calculated per arm and response rates compared between conventional and experimental irradiation arms."}

Secondary endpoints

  • {"endpoint_text":"- First progression of desease, first recurrence, secondary malignancy, death","definition_or_measurement_approach":"Events comprising first disease progression, first recurrence, occurrence of secondary malignancy, and death will be recorded as secondary endpoints (time-to-event assessments such as PFS and OS implied in secondary objectives)."}

Recruitment

Planned Sample Size
81
Recruitment Window Months
119
Consent Approach
Written and signed informed consent from parents or legal guardians will be obtained before starting the treatment. Absence of parents, patient or tutor consent is listed as an exclusion. No details provided on assent procedures, age-specific consent documents, or languages available.

Geography

Total Number Of Sites
5
Total Number Of Participants
81

Italy

Earliest CTIS Part Ii Submission Date
07-05-2024
Latest Decision Or Authorization Date
26-06-2024
Processing Time Days
50
Number Of Sites
5
Number Of Participants
81

Sites

Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Pediatria Oncologica
Principal Investigator Name
Maura Massimino
Principal Investigator Email
maura.massimino@istitutotumori.mi.it
Contact Person Name
Maura Massimino
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
Oncoematologia Pediatrica
Principal Investigator Name
Franca Fagioli
Principal Investigator Email
franca.fagioli@unito.it
Contact Person Name
Franca Fagioli
Contact Person Email
franca.fagioli@unito.it
Site Name
L’Azienda Ospedaliera Di Rilievo Nazionale Santobono-Pausilipon
Department Name
UOC pediatria Oncologica
Principal Investigator Name
Lucia De Martino
Principal Investigator Email
demartinoluci@gmail.com
Contact Person Name
Lucia De Martino
Contact Person Email
demartinoluci@gmail.com
Site Name
IRCCS Istituto Giannina Gaslini
Department Name
Emato-Oncologia
Principal Investigator Name
Claudia Milanaccio
Principal Investigator Email
claudiamilanaccio@gaslini.org
Contact Person Name
Claudia Milanaccio
Contact Person Email
claudiamilanaccio@gaslini.org
Site Name
Bambino Gesu Childrens Hospital
Department Name
Neuro-Oncologia
Principal Investigator Name
Angela Mastronuzzi
Principal Investigator Email
angela.mastronuzzi@opbg.net
Contact Person Name
Angela Mastronuzzi
Contact Person Email
angela.mastronuzzi@opbg.net

Sponsor

Primary sponsor

Full Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Italy

Investigational products

Investigational Product Name
NIMOTUZUMAB
Active Substance
nimotuzumab
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS
Route
Intravenous
Orphan Designation
Yes
Maximum Dose
150 mg/m2
Investigational Product Name
NAVELBINE 10 mg/ml concentrato per soluzione per infusione
Active Substance
vinorelbine tartrate
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
Intravenous
Authorisation Status
Authorised in Italy (marketing authorisation 027865082)
Maximum Dose
25 mg/m2
Combination Treatment
Yes

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