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ISRCTN40708286

A trial of BEvACizumab added to temozolomide +/- irinOtecan for children with refractory/relapsed Neuroblastoma

Datenbasis: WHO (Import vom 14.04.2019)
Geändert: 14.04.2019
Krankheitskategorie:

Health conditions (Datenquelle: WHO)

Neuroblastoma in children aged =1 to =21 years
Cancer
Malignant neoplasm of adrenal gland

Interventions (Datenquelle: WHO)


Current intervention as of 25/03/2019:
Investigational medicinal products: bevacizumab, irinotecan, temozolomide, topotecan, dinutuximab beta, cyclophosphamide

Arm T:
Temozolomide 200 mg/m2 per day oral on days 1-5 every 4 weeks
Duration of intervention: 24 weeks

Arm BT:
Temozolomide 200 mg/m2 per day oral on days 1-5 every 4 weeks
Bevacizumab 10mg/kg intravenous on days 1 and 15 every 4 weeks
Duration of intervention: 24 weeks

Arm IT:
Temozolomide 100 mg/m2 per day oral on days 1-5 every 3 weeks
Irinotecan 50 mg/m2 per day intravenous on days 1-5 every 3 weeks
Duration of intervention: 18 weeks

Arm BIT:
Temozolomide 100 mg/m2 per day oral on days 1-5 every 3 weeks
Irinotecan 50 mg/m2 per day intravenous on days 1-5 every 3 weeks
Bevacizumab 15 mg/kg intravenous on day 1 every 3 weeks
Duration of intervention: 18 weeks

Arm TTo:
Topotecan 0.75 mg/m2/day intravenous on days 1-5 every 4 weeks
Temozolomide 200 mg/m2 per day oral on days 1-5 every 4 weeks
Duration of intervention: 24 weeks

Arm BTTo:
Topotecan 0.75 mg/m2/day intravenous on days 1-5 every 4 weeks
Temozolomide 200 mg/m2 per day oral on days 1-5 every 4 weeks
Bevacizumab 10mg/kg intravenous on days 1 and 15 every 4 weeks
Duration of intervention: 24 weeks

Arm dBT
Dinutuximab beta 10 mg/m2/day 24-h infusion on days 1-7 every 4 weeks
Temozolomide 200 mg/m2/day oral on days 1-5 every 4 weeks
Duration of intervention: 24 weeks

Arm dBTTo
Dinutuximab beta 10 mg/m2/day 24-h infusion on da

Inclusion/Exclusion Criteria (Datenquelle: WHO)

Inclusion criteria:
Disease specific
1. Histologically proven neuroblastoma as per International Neuroblastoma Staging System (INSS) [1] definition
2. Relapsed or refractory neuroblastoma
2.1. Relapsed: any relapsed or progressed high-risk neuroblastoma
2.2. Refractory high risk disease: Lack of adequate response to frontline therapy that precludes the patient from proceeding to consolidation therapies (e.g myeloablative chemotherapy)
3. Measurable disease by cross sectional imaging (RECIST) or evaluable disease (uptake on MIBG scan with or without bone marrow histology). Patients with only bone marrow detectable disease (bone marrow aspirate or trephine) are NOT eligible for the study

General
1. Age =1 to =21 years
2. Informed consent from patient, parent or guardian

Performance and organ function
1. Performance Status:
1.1. Lansky = 50%, Karnofsky = 50% or ECOG =3
(Patients who are unable to walk because of paralysis, but who are able to sit upright unassisted in a wheelchair, will be considered ambulatory for the purpose of assessing performance score)
2. Life expectancy of =12 weeks
3. Bone marrow function (within 72 hours of eligibility assessment):
No bone marrow disease:
1. Platelets = 75 x 109/L (unsupported for 72 hours)
2. ANC = 0.75 x 109/L (no G-CSF support for 72 hours)
3. Haemoglobin > 7.5 g/dL (transfusions allowed)
Bone marrow disease:
1. Platelets = 50 x109/L (unsupported for 72 hours)
2. ANC =0.5 x 109/L (no G-CSF for 72 hours)
3. Haemoglobin > 7.5 g/dL (transfusions allowed)
4. Renal function (within 72 hours of eligibility assessment):
4.1. Absence of clinically significant proteinuria (early morning urine dipstick =2+). When the dipstick urinalysis shows a proteinuria > 2+, a protein:creatinine (Pr/Cr) ratio must be < 0.5 or a 24 hour protein excretion must be < 0.5g
4.2. Serum creatinine =1.5 ULN for age, if higher, a calculated GFR (radioisotope) must be = 60 ml/min/1.73 m2
5. Liver function (within 72 hours of eligibility assessment): AST and ALT =2.5 ULN and total bilirubin =1.5 ULN. In case of liver metastases, AST and ALT =5 ULN and total bilirubin =2.5 ULN
6. Cardiac function, shortening fraction =29% on echocardiogram
7. Coagulation, patients not on anticoagulation must have an INR =1.5 and APTT =1.5 ULN for age. Anticoagulation is permitted as long as the INR or APTT is within therapeutic limits (according to the medical standard of the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of study enrolment. Blood pressure below 95th centile for age and sex. Use of antihypertensive medication is permitted
8. Males or females of reproductive potential may not participate unless they agree to use an effective contraceptive method, for the duration of study therapy and for up to 6 months after the last dose of trial drugs. A negative urine pregnancy test must be obtained within 72 hours prior to dosing in females who are post-menarche

Exclusion criteria:
1. Previous treatment with bevacizumab, temozolomide, irinotecan or any combination of these drugs
2. Known hypersensitivity to:
2.1. Any study drug or component of the formulation
2.2. Chinese hamster ovary products or other recombinant human or humanised antibodies
3. Prior severe arterial thrombo-embolic events (e.g. cardiac ischemia, cerebral vascular accident, peripheral arterial thrombosis)
4. Any ongoing arterial thrombo-embolic events
5. Patient less than (at point of eligibility assessment):
5.1. 48 hours post bone marrow aspirate/trephine
5.2. 48 hours post central line insertion
5.3. Four weeks post major surgery
5.4. One week post core biopsy
5.5. Two weeks from prior chemotherapy
5.6. Six weeks from prior craniospinal or MIBG therapy and two weeks from radiotherapy to the tumour bed
5.7. Eight weeks from prior myeloablative therapy with haematopoeitic stem cell rescue (autologous stem cell transplant)
5.8. Three months from prior allogeneic stem cell transplant
5.9. Two weeks from last administration of an IMP in an IMP-trial
6. Bleeding metastases (patients with CNS metastases can be enrolled as long as the metastases are not bleeding)
7. Invasion of major blood vessels
8. Use of enzyme inducing anticonvulsants within 72 hours of eligibility assessment
9. History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation)
10. History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to study enrolment
11. Pregnant or lactating patient
12. Any uncontrolled medical condition that poses an additional risk to the patient (i.e. haemoptysis, non-healing, bone fracture, wound/ulcer)
13. Low probability of treatment compliance
14. Planned immunisation with live vaccine

Weitere Angaben zur Studie im WHO-Primärregister

http://isrctn.com/ISRCTN40708286

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN40708286

Weitere Informationen zur Studie

Registrationsdatum der Studie

24.04.2013

Einschluss der ersten teilnehmenden Person

01.04.2013

Rekrutierungsstatus

Completed

Wissenschaftlicher Titel (Datenquelle: WHO)

A randomised phase IIb trial of BEvACizumab added to temozolomide +/- irinOtecan for children with refractory/relapsed Neuroblastoma

Studientyp (Datenquelle: WHO)

Interventional

Design der Studie (Datenquelle: WHO)

Interventional phase II randomised open label international multicentre 2x2 factorial trial (Treatment)

Phase (Datenquelle: WHO)

Phase II

Primäre Endpunkte (Datenquelle: WHO)

Best response (Complete Response [CR], or Partial Response [PR][1] at any time during the first 6 cycles of trial treatment

Sekundäre Endpunkte (Datenquelle: WHO)


1. Safety of the regimens: Incidence and severity of Adverse Events (AEs)
2. Progression-free survival (PFS)
3. Overall survival (OS)

Kontakt für Auskünfte (Datenquelle: WHO)

Cancer Research UK (UK) - Clinical Trials Awards & Advisory Committee: C1536/A14426

Studiendurchführungsorte

Durchführungsländer (Datenquelle: WHO)

Austria, Belgium, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, Switzerland, United Kingdom

Kontakt für weitere Auskünfte zur Studie

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Lucas
Moreno
CNIO-HNJ Clinical Trials Unit Hospital Infantil Universitario Niño Jesús Av Menendez Pelayo 65
+44 21 414 8040
lucas.moreno@salud.madrid.org

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

University of Birmingham

Weitere Studienidentifikationsnummern

Secondary ID (Datenquelle: WHO)

2012-000072-42