Activity Study of Bevacizumab With Temozolomide ± Irinotecan for Neuroblastoma in Children

Sponsor
University of Birmingham
Study ID
NCT02308527
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
1 Year - 21 Years
Healthy Volunteers
Not accepted

Interventions

  • Bevacizumab — DRUG
    10mg/kg IV (in the vein) on Days 1 and 15 of a 4 week cycle, for 6 cycles or until progression
  • Temozolomide — DRUG
    200mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression
  • Temozolomide — DRUG
    100mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 3 week cycle, for 6 cycles or until progression
  • Irinotecan — DRUG
    50mg/m2/d IV (in the vein) on Days 1 to 5 of a 3 week cycle, for 6 cycles or until progression
  • Bevacizumab — DRUG
    15mg/kg IV (in the vein) on Day 1 of a 3 week cycle, for 6 cycles or until progression
  • Topotecan — DRUG
    0.75mg/m2/d IV (in the vein) on Days 1-5 of a 4 week cycle, for 6 cycles or until progression
  • Temozolomide — DRUG
    150mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression
  • Dinutuximab Beta — DRUG
    10mg/m2/d IV (in the vein) on Days 1 to 7 of a 4 week cycle, for 6 cycles or until progression
  • Cyclophosphamide — DRUG
    250mg/m2/d IV (in the vein) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression

Study Details

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)? NOTE- This question has been completed. * 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) NOTE - This question has been completed. * does the addition of dinutuximab beta added to a backbone chemotherapy (temozolomide or temozolomide + topotecan) increase the effect of backbone alone. 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.

Key Dates

Start date
Jul 31, 2013
Status verified
Apr 2026
Primary completion
Aug 1, 2021
Completion
Feb 18, 2026

Study Design

Enrollment
225 participants (actual)
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Temozolomide
    Temozolomide Days 1-5 every 4 weeks
  • Experimental: Bevacizumab + Temozolomide
    Bevacizumab Day 1 and 15 + Temozolomide Days 1-5 every 4 weeks
  • Experimental: Irinotecan + Temozolomide
    Irinotecan Days 1-5 + Temozolomide Days 1-5 every 3 weeks
  • Experimental: Bevacizumab + Irinotecan + Temozolomide
    Bevacizumab Day 1 + Irinotecan Days 1-5 + Temozolomide Days 1-5 every 3 weeks
  • Experimental: Temozolomide + Topotecan
    Temozolomide Days 1-5+ Topotecan Days 1-5 every 4 weeks
  • Experimental: Bevacizumab + Temozolomide + Topotecan
    Bevacizumab Day 1 and 15 + Temozolomide Days 1-5 + Topotecan Days 1-5 every 4 weeks
  • Experimental: Dinutuximab beta + Temozolomide
    Dinutuximab beta Days 1-7 + Temozolomide Days 1-5 every 4 weeks
  • Experimental: Dinutuximab beta + Temozolomide + Topotecan
    Dinutuximab beta Days 1-7 + Temozolomide Days 1-5 + Topotecan Days 1-5 every 4 weeks
  • Other: Dinutuximab beta + Topotecan + Cyclophosphamide
    Dinutuximab beta Days 1-7 + Topotecan Days 1-5 + Cyclophosphamide Days 1-5 every 4 weeks

Primary Outcome Measure

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. [ Time Frame: Within 18 or 24 weeks depending on the arm of the trial the participant is randomised to. ]

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