An international trial for children with atypical teratoid/rhabdoid tumours (ATRT)
- Conditions
- atypical teratoid/rhabdoid tumours (ATRT)MedDRA version: 21.0Level: PTClassification code 10006131Term: Brain neoplasm malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003335-29-DK
- Lead Sponsor
- German Pediatric Oncology Group, GPOH gGmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 152
Registration Into Umbrella Trial
- Age at diagnosis less than 18 years
- Pathology compatible with ATRT and INI1 loss or SMARCB1 or SMARCA4 deficiency confirmed by local pathology lab
- Written informed consent and/or assent for study participation according to national legislation
- Patient agrees to use effective contraception whilst on treatment (patients of childbearing potential)
Part A:
1 Enrolled in the umbrella trial
2. Received 3 courses of induction chemotherapy according to the protocol and following induction in SD or better
3. Expected age 12-35 months at time of consolidation therapy (RT or HDCT)
4. Written informed consent and/or assent for randomization according to national legislation
5. Central review of pathology confirmed ATRT
6. MRI and CSF examination after 3 courses of chemotherapy and, if applicable, later showing SD or better (central review – national or regional centre)
7. ALT or AST =3.0 x ULN, bilirubin = 1.5 x ULN
8. Creatinine = 1.5 x ULN and measured GFR within published defined age-related values according to national standard methods.
9. EF =50% or FS =29% by echocardiography.
Part B:
1. Enrolled in the umbrella trial
2. Received 3 courses of induction chemotherapy according to the protocol
3. Radiotherapy not admissible (e.g. <12 months or other contraindications)
4. Not eligible for the randomized trial (Part A) (e.g. refusal of randomization)
5. Written informed consent and/or assent for inclusion according to national legislation
6. Central review of pathology confirmed ATRT
7. 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)
8. ALT or AST =3.0 x ULN, bilirubin = 1.5 x ULN
9. Creatinine = 1.5 x ULN and measured GFR within published defined age-related values according to national standard methods.
10. EF =50% or FS =29% by echocardiography.
Part C:
1. Enrolled in the umbrella trial
2. Received 3 courses of induction chemotherapy according to the protocol
3. Aged 36 months or above OR
4. HDCT not possible OR
5. Not eligible for the randomized trial (Part A)
6. Written informed consent and/or assent for inclusion according to national legislation
7. Central review of pathology confirmed ATRT
8. MRI and CSF examination after 3 courses of chemotherapy and, if applicable, later showing SD or better (central review – national or regional centre)
9. ALT or AST =3.0 x ULN, bilirubin = 1.5 x ULN
10. Creatinine = 1.5 x ULN and measured GFR within published defined age-related values according to national standard methods.
11. EF =50% or FS =29% by echocardiography
Are the trial subjects under 18? yes
Number of subjects for this age range: 152
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Part A:
1. Previous or concomitant tumour directed chemotherapy, RT or small molecule therapy, other than within the SIOPE ATRT01 trial
2. Metastatic disease at primary diagnosis
3. At time of inclusion Diarrhoea grade 3 or worse according to the CTCAE v5.0, if uncontrolled despite optimal supportive therapy
4. 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,
5. 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
6. Pulmonary hypertension as diagnosed by a paediatric cardiologist with indirect (echocardiography) or direct signs (pulmonary artery pressure =25mmHg)
7. Any contraindication to any planned chemotherapy drug according to SmPC
8. Known active HBV, HCV or HIV infection
9. Participation in another interventional therapeutic clinical trial
10. Patients on coumarin-derivative anticoagulants
11. History of thrombosis or SOS
12. Any ongoing, uncontrolled, clinically significant infection (viral, bacterial or fungal)
13. Neutropenia (ANC <0.5 x109/L) lasting 6 weeks from the start of the previous course of chemotherapy
14. Synchronous multifocal rhabdoid tumours
15. Hypersensitivity to the active compounds or other
Part B:
1. Previous or concomitant tumour directed chemotherapy, radiotherapy or small molecule therapy, other than within the SIOPE ATRT01 trial
2. At time of inclusion Diarrhoea grade 3 or worse according to the CTCAE v5.0, if uncontrolled despite optimal supportive therapy
3. 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
4. Pulmonary hypertension as diagnosed by a paediatric cardiologist with indirect (echocardiography) or direct signs (pulmonary artery pressure =25mmHg)
5. Any contraindication to any planned chemotherapy drug according to SmPC
6. Known active HBV, HCV or HIV infection
7. Participation in another interventional therapeutic clinical trial
8. Patients on coumarin-derivative anticoagulants
9. History of thrombosis or SOS
10. Any ongoing, uncontrolled, clinically significant infection (viral, bacterial or fungal)
11. Neutropenia (ANC <0.5 x109/L) lasting 6 weeks from the start of the previous course of chemotherapy
12. Hypersensitivity to the active substance or other excipients contained in one of the investigational medical products listed in the SmPC.
Part C:
1. Previous or concomitant tumour directed chemotherapy, RT or small molecule therapy, other than within the SIOPE ATRT01 trial
2. Any contraindication to any planned chemotherapy drug according to SmPC
3. Participation in another interventional therapeutic clinical trial
4. Any ongoing, uncontrolled, clinically significant infection (viral, bacterial or fungal)
5. Hypersensitivity to the active substance or other excipients contained in one of the investigational medical products listed in the SmPC.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method