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

Summary

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.

Conditions

• Neuroblastoma

Interventions

DRUG

Dinutuximab Beta

10mg/m2/d IV (in the vein) on Days 1 to 7 of a 4 week cycle, for 6 cycles or until progression

DRUG

Cyclophosphamide

250mg/m2/d IV (in the vein) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression

DRUG

Temozolomide

150mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression

DRUG

Irinotecan

50mg/m2/d IV (in the vein) on Days 1 to 5 of a 3 week cycle, for 6 cycles or until progression

DRUG

Bevacizumab

15mg/kg IV (in the vein) on Day 1 of a 3 week cycle, for 6 cycles or until progression

DRUG

Topotecan

0.75mg/m2/d IV (in the vein) on Days 1-5 of a 4 week cycle, for 6 cycles or until progression

DRUG

Bevacizumab

10mg/kg IV (in the vein) on Days 1 and 15 of a 4 week cycle, for 6 cycles or until progression

DRUG

Temozolomide

200mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression

DRUG

Temozolomide

100mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 3 week cycle, for 6 cycles or until progression

Sponsors & Collaborators

• Cancer Research UK

  collaborator OTHER

• Roche Pharma AG

  collaborator INDUSTRY

• Imagine for Margo

  collaborator UNKNOWN

• EUSA Pharma, Inc.

  collaborator INDUSTRY

• University of Birmingham

  lead OTHER

Principal Investigators

• Lucas Moreno, MD · University of Birmingham

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

1 Year

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-07-31

Primary Completion

2021-08-01

Completion

2026-02-18

Countries

• Austria
• Belgium
• Denmark
• France
• Ireland
• Italy
• Netherlands
• Spain
• Switzerland
• United Kingdom

Study Locations