Phase 2 open label randomized study of radiotherapy, concomitant nimotuzumab and vinorelbine and re-irradiation at relapse versus radiotherapy and multiple elective radiotherapy courses with concomitant vinorelbine and nimotuzumab for newly diagnosed childhood and adolescence diffuse intrinsic pontine glioma (DIPG).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione IRCCS Istituto Nazionale Dei Tumori

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Nov 2015 → ongoing

Decision date (initial)

2024-06-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-513654-30-00

EudraCT number

2015-002185-23

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Others, Efficacy, Safety, Therapy

Primary aim of this study will be compare the best response up to 36 weeks (CR+PR) between conventional and experimental irradiation.

Secondary objectives 5

1. Compare the disease stabilization rate (considering SD only) up to week 36 between the two arms. The evaluation will be done according to radiological and clinical criteria
2. Compare PFS and OS between the two arms
3. Assess safety of radiotherapy
4. Assess the quality of life and life situation
5. Assess PFS and OS of diffuse midline glioma with K27 mutation using the standard arm of the main protocol

Conditions and MedDRA coding

Diffuse intrinsic pontine glioma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients from 2 to 21 years old will be eligible
2. No previous treatment consented apart from steroids
3. 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]
4. Symptoms lasting less than 6 months, life expectancy ≥4 weeks; Karnowski/Lansky performance status ≥ 40 %
5. No organ dysfunction; no pregnancy or breast-feeding
6. 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
7. Written and signed informed consent from parents or legal guardians will be obtained before starting the treatment
8. 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 9

1. Patients below 2 years or over 21
2. Pre-treatment with radio or chemotherapy
3. Neurofibromatosis 1
4. Non-typical imaging
5. Symptoms duration over 6 months, Lansky/Karnowski scores below 40%
6. Metastatic disease as shown by MRI
7. Organ dysfunction, pregnancy or breast-feeding
8. Absence of parents, patient or tutor consent
9. Not central review diagnosis of diffuse midline glioma histone H3, K27 mutated

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 1

1. First progression of desease, first recurrence, secondary malignancy, death

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS Istituto Nazionale Dei Tumori

Sponsor organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Address

Via Giacomo Venezian 1

City

Milan

Postcode

20133

Country

Italy

Scientific contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Pediatria Oncologica

Public contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Public Relation Office

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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