Last updated on July 2019

Activity Study of Bevacizumab With Temozolomide Irinotecan for Neuroblastoma in Children


Brief description of study

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:

  • does targeting blood vessel development using bevacizumab, (a monoclonal antibody against the Vascular Endothelial Growth Factor (VEGF)), add to the effect on a tumour when used with existing chemotherapy, compared to the effect of the existing chemotherapy alone (temozolomide)?
  • does the addition of a second chemotherapy drug (irinotecan or topotecan) increase the effect on a tumour compared to the effect of one alone (temozolomide) Patients aged 1-21 years of age with relapsed or refractory high-risk neuroblastoma are randomised to one of six treatment arms: Temozolomide (T), irinotecan-temozolomide (IT), bevacizumab-T (BT), BIT (bevacizumab-IT), temozolomide-topotecan (TTo) or bevacizumab-temozolomide-topotecan (BTTo).

Detailed Study Description

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 six arms (approximately 30 patients per arm):

T: Temozolomide BT: Bevacizumab + Temozolomide IT: Irinotecan + Temozolomide BIT: Bevacizumab + Irinotecan + Temozolomide TTo: Temozolomide + Topotecan BTTo: Bevacizumab + Temozolomide + Topotecan

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 1:1 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 18 or 24 weeks depending on the arm of the trial that they are randomised to.

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).

Clinical Study Identifier: NCT02308527

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