An international trial for children with atypical teratoid/rhabdoid tumours (ATRT)

Trial details

Who runs it

GPOH gGmbH

Trial code

EU 2022-501456-28-00

Record updated

2026. szeptember 14.

Original description

Part A: To test the non-inferiority, as evaluated by OS, of three courses of HDCT compared to focal RT plus conventional chemotherapy as consolidation therapy following conventional chemotherapy in children with ATRT aged 12 – 35 months at consolidation therapy. Part B: To assess the efficacy, as evaluated by OS, of three courses of HDCT as a consolidation measure following conventional-type chemotherapy in children with ATRT aged <12 months at the time of HDCT and not eligible for randomization within Part A of this protocol, compared to historical controls. Part C: To assess the efficacy, as evaluated by overall survival, of RT as a consolidation measure combined with conventional-type chemotherapy in children aged ≥36 months with ATRT, compared to historical controls.Read full original descriptionShow less

An international prospective umbrella trial for children with atypical teratoid/rhabdoid tumours (ATRT) including a randomized phase III study evaluating the non-inferiority of three courses of high-dose chemotherapy (HDCT) compared to focal radiotherapy as consolidation therapy

Part A: To test the non-inferiority, as evaluated by OS, of three courses of HDCT compared to focal RT plus conventional chemotherapy as consolidation therapy following conventional chemotherapy in children with ATRT aged 12 – 35 months at consolidation therapy. Part B: To assess the efficacy, as evaluated by OS, of three courses of HDCT as a consolidation measure following conventional-type chemotherapy in children with ATRT aged <12 months at the time of HDCT and not eligible for randomization within Part A of this protocol, compared to historical controls. Part C: To assess the efficacy, as evaluated by overall survival, of RT as a consolidation measure combined with conventional-type chemotherapy in children aged ≥36 months with ATRT, compared to historical controls.

Inclusion: Umbrella: Age at diagnosis less than 18 years; Part A: MRI and CSF examination after 3 courses of chemotherapy and, if applicable, later showing SD or better (central review – national or regional centre); Part A: ALT or AST ≤3.0 x ULN, bilirubin ≤ 1.5 x ULN; Part A: Creatinine ≤ 1.5 x ULN and measured GFR within normal published defined age-related values according to national standard methods; Part A: EF ≥50% or FS ≥29% by echocardiography; Part B: Enrolled in the umbrella trial; Part B: Received 3 courses of induction chemotherapy according to the protocol; Part B: Radiotherapy not admissible (e.g. <12 months or other contraindications); Part B: Not eligible for the randomized trial (Part A) (e.g. refusal of randomization); Part B: Written informed consent and/or assent for inclusion according to national legislation; Part B: Central review of pathology confirmed ATRT; Umbrella: Pathology compatible with ATRT and INI1 loss or SMARCB1 or SMARCA4 deficiency confirmed by local pathology lab; Part B: MRI and CSF examination after 3 courses of chemotherapy and, if applicable, later showing clinically significant sensitivity to chemotherapy (central review – national or regional centre); Part B: ALT or AST ≤3.0 x ULN, bilirubin ≤ 1.5 x ULN; Part B: Creatinine ≤ 1.5 x ULN and measured GFR within normal published defined age-related values according to national standard methods; Part B: EF ≥50% or FS ≥29% by echocardiography; Part C: Enrolled in the umbrella trial; Part C: Received 3 courses of induction chemotherapy according to the protocol; Part C: Aged 36 months or above OR HDCT not possible OR Not eligible for the randomized trial (Part A); Part C: Written informed consent and/or assent for inclusion according to national legislation; Part C: Central review of pathology confirmed ATRT; Part C: MRI and CSF examination after 3 courses of chemotherapy and, if applicable, later showing SD or better (central review – national or regional centre); Umbrella: Written informed consent and/or assent for trial participation according to national legislation; Part C: ALT or AST ≤3.0 x ULN, bilirubin ≤ 1.5 x ULN; Part C: Creatinine ≤ 1.5 x ULN and measured GFR within normal published defined age-related values according to national standard methods; Part C: EF ≥50% or FS ≥29% by echocardiography; Umbrella: Patient agrees to use effective contraception whilst on treatment; Part A: Enrolled in the umbrella trial; Part A: Received 3 courses of induction chemotherapy according to the protocol and following induction in SD or better; Part A: Expected age 12-35 months at time of consolidation therapy (RT or HDCT); Part A: Written informed consent and/or assent for randomization according to national legislation; Part A: Central review of pathology confirmed ATRT.

Exclusion: Part A: Previous or concomitant tumour directed chemotherapy, RT or small molecule therapy, other than within the SIOPE ATRT01 trial; Part B: Any contraindication to any planned chemotherapy drug according to SmPC; Part C: Previous or concomitant tumour directed chemotherapy, RT or small molecule therapy, other than within the SIOPE ATRT01 trial; Part C: Any contraindication to any planned chemotherapy drug according to SmPC; Part A: Any contraindication to any planned chemotherapy drug according to SmPC; Umbrella: Any contraindications to any planned conventional chemotherapy drug according to SmPC; Umbrella: Previous or concomitant tumour directed chemotherapy (more than one course of standard treatment), RT or small molecule therapy, other than within the SIOPE ATRT01 trial; Umbrella: Receipt of a live attenuated vaccine 30 days or fewer prior to inclusion or planned vaccination with a live attenuated vaccine during treatment or within 3 months after the last dose administration; Part A: Receipt of a live attenuated vaccine 30 days or fewer prior to inclusion or planned vaccination with a live attenuated vaccine during treatment or within 3 months after the last dose administration; Part B: Receipt of a live attenuated vaccine 30 days or fewer prior to inclusion or planned vaccination with a live attenuated vaccine during treatment or within 3 months after the last dose administration; Part C: Receipt of a live attenuated vaccine 30 days or fewer prior to inclusion or planned vaccination with a live attenuated vaccine during treatment or within 3 months after the last dose administration; Part B: Previous or concomitant tumour directed chemotherapy, radiotherapy or small molecule therapy, other than within the SIOPE ATRT01 trial; Part B: At time of inclusion Diarrhoea grade 3 or worse according to the CTCAE v5.0, if uncontrolled despite optimal supportive therapy; Part B: Pulmonary hypertension as diagnosed by a paediatric cardiologist with indirect (echocardiography) or direct signs (pulmonary artery pressure ≥25mmHg); Part A: Metastatic disease at primary diagnosis; Part B: Known active HBV, HCV or HIV infection; Part B: History of thrombosis or SOS; Part B: Any ongoing, uncontrolled, clinically significant infection (viral, bacterial or fungal); Part B: Hypersensitivity to the active substance or other excipients contained in one of the investigational medical products listed in the SmPC; Part A: History of thrombosis or SOS; Part A: History or presence of clinically significant cardiac disease, including, but not limited to, any of the following, if uncontrolled despite optimal supportive care: a. Sustained ventricular tachyarrhythmia b. Any ventricular fibrillation or torsade de pointes; Part C: Any ongoing, uncontrolled, clinically significant infection (viral, bacterial or fungal); Part C: Hypersensitivity to the active substance or other excipients contained in one of the investigational medical products listed in the SmPC; Part A: At time of inclusion bradycardia defined as persistent heart rate < 50/minute if uncontrolled despite optimal supportive therapy Screening ECG with a QTcB >450msec minute if uncontrolled despite optimal supportive therapy; Part A: Pulmonary hypertension as diagnosed by a paediatric cardiologist with indirect (echocardiography) or direct signs (pulmonary artery pressure ≥25mmHg); Part A: Known active HBV, HCV or HIV infection; Part A: Any ongoing, uncontrolled, clinically significant infection (viral, bacterial or fungal); Umbrella: Hypersensitivity to the active compounds or other excipients contained in one of the investigational medical products listed in the SmPC; Umbrella: Any ongoing, uncontrolled, clinically significant infection (viral, bacterial or fungal); Umbrella: History or presence of non-infectious pneumonitis requiring steroids; Part A: History or presence of non-infectious pneumonitis requiring steroids; Part B: History or presence of non-infectious pneumonitis requiring steroids; Part C: History or presence of non-infectious pneumonitis requiring steroids; Part A: Hypersensitivity to the active compounds or other; Part B: History or presence of clinically significant cardiac disease, including, but not limited to, any of the following, if uncontrolled despite optimal supportive therapy: a. Sustained ventricular tachyarrhythmia b. Any ventricular fibrillation or torsade de pointes c. Current bradycardia defined as heart rate < 50/minute d. Screening ECG with a QTcB >450msec; Part B: Neutropenia (ANC <0.5 x109/L) lasting 6 weeks from the start of the previous course of chemotherapy; Part A: Neutropenia (ANC <0.5 x109/L) lasting 6 weeks from the start of the previous course of chemotherapy; Part B: Participation in another interventional therapeutic clinical trial; Part B: Patients on coumarin-derivative anticoagulants; Part C: Participation in another interventional therapeutic clinical trial; Part A: Participation in another interventional therapeutic clinical trial; Part A: Patients on coumarin-derivative anticoagulants; Umbrella: Participation in another interventional therapeutic clinical trial; Umbrella: Pregnancy or breastfeeding; Part A: Pregnancy or breastfeeding; Part B: Pregnancy or breastfeeding; Part C: Pregnancy or breastfeeding; Part A: Synchronous multifocal rhabdoid tumours.

EU CTIS 2022-501456-28-00