A Phase 2 interventional study of Bevacizumab and Temozolomide in Neuroblastoma, sponsored by University of Birmingham. Completed at 10 sites in 10 countries. Open to participants aged 1 Year to 21 Years. Per ClinicalTrials.gov, last updated 2026-05-12.
Sponsored by University of Birmingham · Phase 2, Interventional, and Treatment
The purpose of this study is to investigate whether Bevacizumab (an anti-VEGF monoclonal antibody) added to a backbone chemotherapy regimen (Temozolomide, Irinotecan-Temozolomide or Topotecan-Temozolomide) demonstrates activity in children with relapsed or refractory neuroblastoma. Also, to investigate whether the addition of Irinotecan or Topotecan to Temozolomide increases the activity of chemotherapy.The primary objective of the study is the best response (Complete Response or Partial Response) while trial treatment, within 18 or 24 weeks depending on the arm of the trial the participant is randomised to. Secondary endpoints are assessing the side effects, the length of time before progression (Progression Free Survival) and overall survival (OS).
This trial will address two important questions:
Patients aged 1-21 years of age with relapsed or refractory high-risk neuroblastoma are randomised to one of two treatment arms: temozolomide-topotecan (TTo) or dinutuximab beta-temozolomide-topotecan (dBTTo). Temozolomide (T), irinotecan-temozolomide (IT), bevacizumab-T (BT), BIT (bevacizumab-IT), bevacizumab-temozolomide-topotecan (BTTo) and dinutuximab beta-temozolomide (dBT) are now closed to recruitment.
This is an international open-label, randomised, multicentre phase II trial of temozolomide ± irinotecan, with or without bevacizumab, for the treatment of patients with relapsed or refractory neuroblastoma. The study will evaluate the safety and activity of these combinations.
Patients will be registered into the trial and randomised at the same time to one of the following two arms (approximately 30 patients per arm):
TTo: Temozolomide + Topotecan dBTTo: Dinuximab beta + Temozolomide + Topotecan
Arms which have now closed to recruitment:
dBT: Dinutuximab beat + Temozolomide Closed 28 ]Jan 2020 T: Temozolomide - Closed 28 Jan 2020 BT: Bevacizumab + Temozolomide - Closed 7 Feb 2019 IT: Irinotecan + Temozolomide - Closed 21 June 2018 BIT: Bevacizumab + Irinotecan + Temozolomide - Closed 21 June 2018 BTTo: Bevacizumab + Temozolomide + Topotecan - Closed 7 Feb 2019
Randomisation will be via a secure on-line computer-based system at the Cancer Research Clinical Trial Unit (CRCTU), University of Birmingham, United Kingdom (UK) and patients will be allocated in a 2:1 ratio. Minimisation will be used to ensure balance across the arms for the important prognostic factors as described by London et al. [10]: a) relapsed, refractory disease, b) early (\< 18 months), late relapse (≥18 months) and c) measurable versus evaluable disease (i.e. disease evaluated according to RECIST versus disease detectable only by MIBG scanning with or without bone marrow involvement as detected by local morphology) Patients will receive treatment for 6 courses, lasting 24 weeks.
Patients with a response (CR, PR) or stable disease (SD) while on the BEACON-Neuroblastoma trial will receive 6 cycles of trial treatment. If the patient has achieved a satisfactory response (i.e. CR, PR or SD) with acceptable toxicity, treatment may be extended beyond 6 cycles (up to 12 cycles) after discussion with the Sponsor and the Chief Investigator (CI).
In addition, patients randomised to TTo may recieve an optional regimen of dinutuximab beta + topotecan + cyclophosphamide (up to 6 cycles).
625 studies on the registry are indexed under Neuroblastoma; 122 are open to participants now.
This study's enrollment of 225 is above the median of 32 across 475 interventional studies indexed under Neuroblastoma.
Browse Neuroblastoma studies →University of Birmingham is the lead sponsor of 179 studies on the registry; 30 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Temozolomide Days 1-5 every 4 weeks
Drug: Temozolomide
Bevacizumab Day 1 and 15 + Temozolomide Days 1-5 every 4 weeks
Drug: Bevacizumab · Drug: Temozolomide
Irinotecan Days 1-5 + Temozolomide Days 1-5 every 3 weeks
Drug: Temozolomide · Drug: Irinotecan
Bevacizumab Day 1 + Irinotecan Days 1-5 + Temozolomide Days 1-5 every 3 weeks
Drug: Temozolomide · Drug: Irinotecan · Drug: Bevacizumab
Temozolomide Days 1-5+ Topotecan Days 1-5 every 4 weeks
Drug: Topotecan · Drug: Temozolomide
Bevacizumab Day 1 and 15 + Temozolomide Days 1-5 + Topotecan Days 1-5 every 4 weeks
Drug: Bevacizumab · Drug: Topotecan · Drug: Temozolomide
Dinutuximab beta Days 1-7 + Temozolomide Days 1-5 every 4 weeks
Drug: Temozolomide · Drug: Dinutuximab Beta
Dinutuximab beta Days 1-7 + Temozolomide Days 1-5 + Topotecan Days 1-5 every 4 weeks
Drug: Temozolomide · Drug: Topotecan · Drug: Dinutuximab Beta
Dinutuximab beta Days 1-7 + Topotecan Days 1-5 + Cyclophosphamide Days 1-5 every 4 weeks
Drug: Topotecan · Drug: Dinutuximab Beta · Drug: Cyclophosphamide
10mg/kg IV (in the vein) on Days 1 and 15 of a 4 week cycle, for 6 cycles or until progression
Also known as: Avastin
200mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression
Also known as: Temodal
100mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 3 week cycle, for 6 cycles or until progression
Also known as: Temodal
50mg/m2/d IV (in the vein) on Days 1 to 5 of a 3 week cycle, for 6 cycles or until progression
Also known as: Campto
15mg/kg IV (in the vein) on Day 1 of a 3 week cycle, for 6 cycles or until progression
Also known as: Avastin
0.75mg/m2/d IV (in the vein) on Days 1-5 of a 4 week cycle, for 6 cycles or until progression
150mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression
Also known as: Temodal
10mg/m2/d IV (in the vein) on Days 1 to 7 of a 4 week cycle, for 6 cycles or until progression
Also known as: Qarziba
250mg/m2/d IV (in the vein) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression
Best response (Complete Response or Partial Response) while on trial treatment, within 18 or 24 weeks depending on the arm of the trial participant is randomised to.
* To test whether bevacizumab added to a backbone chemotherapy regimen (temozolomide, irinotecan-temozolomide or topotecan-temozolomide) demonstrates activity in children with relapsed or refractory neuroblastoma * To test whether the addition of irinotecan to temozolomide increases the activity of chemotherapy in children with relapsed or refractory neuroblastoma * To test whether the addition of topotecan to temozolomide increases the activity of chemotherapy in children with relapsed or refractory neuroblastoma ("topotecan randomisation") * To test whether dinutuximab beta added to a backbone chemotherapy regimen (temozolomide or temozolomide + topotecan) demonstrates activity in children with relapsed or refractory neuroblastoma ("dinutuximab beta randomisation)
Time frame: Within 18 or 24 weeks depending on the arm of the trial the participant is randomised to.
For the bevacizumab part 2 only; Progression-free survival (PFS)
Progression-free survival (PFS)
Time frame: Assessment will be after 30 days after treatment or end of trial
To evaluate the toxicity of the regimens
Safety of the regimens: Incidence and severity of Adverse Events (AE)s
Time frame: Assessment will be after 30 days after treatment or end of trial
To evaluate the safety of the regimens
Safety of the regimens: Progression-free survival (PFS)
Time frame: Assessment will be after 30 days after treatment or end of trial
To evaluate the overall safety of the regimens
Safety of the regimens: Overall survival (OS)
Time frame: Assessment will be after 30 days after treatment or end of trial
To evaluate the safety of the regimens
Safety of the regimens: Event-free survival (EFS)
Time frame: Assessment will be after 30 days after treatment or end of trial
Plan to share: No
This study is completed, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
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University of Birmingham