NeuroblastomaPhase 2BEACONNCT02308527
Activity Study of Bevacizumab With Temozolomide ± Irinotecan for Neuroblastoma in Children
A Phase 2 study testing Bevacizumab, Temozolomide and Irinotecan in people with Neuroblastoma, run by University of Birmingham at 10 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Bevacizumab, Temozolomide and Irinotecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 225 participants
- Where
- 10 sitesin 10 countries
- Study dates
- Jul 2013to 18 Feb 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically proven neuroblastoma as per International Neuroblastoma Staging System (INSS) definition
- Relapsed: any relapsed or progressed high-risk neuroblastoma
- Refractory high risk disease: Lack of adequate response to frontline therapy that precludes the patient from proceeding to consolidation therapies
- Measurable disease by cross sectional imaging (RECIST) or evaluable disease
- Age ≥1 to ≤21 years
- Informed consent from patient, parent or guardian
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- Performance Status:Lansky ≥ 50%, Karnofsky ≥ 50% or Eastern Cooperative Oncology Group ≤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)
- Life expectancy of ≥12 weeks
- No bone marrow disease: Platelets ≥75 x 10^9/L (unsupported for 72 hours), absolute neutrophil count ≥0.75 x10^9/L (no G-cerebrospinal fluid support for 72 hours), Haemoglobin ≥8 g/dL (transfusions allowed) Bone marrow disease: Platelets ≥50 x10^9/L (unsupported for 72 hours), absolute neutrophil count (ANC) ≥0.5 x 10^9/L (no granulocyte colony stimulating factor (G-CSF) for 72 hours), Haemoglobin ≥8 g/dL (transfusions allowed)
- Renal function (within 72 hours of eligibility assessment): 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
- Serum creatinine ≤ 1.5 upper limit of normal for age, if higher, a calculated glomerular filtration rate (radioisotope) must be ≥60 ml/min/1.73 m2
- Liver function (within 72 hours of eligibility assessment): aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) ≤2.5 ULN and Total bilirubin ≤1.5 upper limit of normal (ULN). In case of liver metastases, AST or ALT ≤5 ULN and Total bilirubin ≤2.5 ULN
- Cardiac function, shortening fraction ≥29% on echocardiogram
- Coagulation, patients not on anticoagulation must have an international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5 ULN for age. Anti-coagulation 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
- 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
- No dyspnoea at rest and pulse oximetry > 94% in room air
- Availability and willingness to place a double central venous access if needed for trial treatment and supportive care in case of treatment with chemo-immunotherapy
Who cannot join
- Previous treatment with bevacizumab, temozolomide, irinotecan or any combination of these drugs
- Known hypersensitivity to: Any study drug or component of the formulation, Chinese hamster ovary products or other recombinant human or humanised antibodies, Dacarbazine
- Prior severe arterial thrombo-embolic events (e.g. cardiac ischemia, cerebral vascular accident, peripheral arterial thrombosis)
- Any ongoing arterial thrombo-embolic events
- Patient less than (at point of planned date of randomisation): 48 hours post bone marrow aspirate/trephine, 48 hours post central line insertion, Four weeks post major surgery, One week post core biopsy, Two weeks from prior chemotherapy, Six weeks from prior craniospinal radiotherapy or MIBG therapy and two weeks from radiotherapy to the tumour bed, Eight weeks from prior myeloablative therapy with haematopoietic stem cell rescue (autologous stem cell transplant), Three months from prior allogeneic stem cell transplant, 14 days or 5 half-lives (whichever occurs later) from last administration of an IMP in an IMP-trial, 6 months from presentation of lung haemorrhage/haemoptysis
- Bleeding metastases (patients with CNS metastases can be enrolled as long as the metastases are not bleeding)
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- Invasion of major blood vessels
- Use of enzyme inducing anticonvulsants within 72 hours of randomisation
- History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation)
- History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to study enrolment
- Current chronic intestinal inflammatory disease/bowel obstruction
- Intolerance to galactose and fructose, lactase deficiency, and/or defect of absorption of galactose and fructose
- Pregnant or lactating patient
- Any uncontrolled medical condition that poses an additional risk to the patient (i.e. haemoptysis, non-healing, bone fracture, wound/ulcer)
- Low probability of treatment compliance
- Any uncontrolled medical condition that poses an additional risk to the patient
- Planned immunisation with live vaccine
Trial locations and contacts
10 sites in 10 countries.
10 sites in 10 countries
Austria1 site
St Anna Children's Hospital and CCRI/Studies and Statistics
Vienna, A-1090
United Kingdom1 site
The Royal Marsden NHS Foundation Trust and Institute of Cancer Research
Sutton, Surrey, SM2 5PT
About this study
Official title: A Randomised Phase IIb Trial of Bevacizumab Added to Temozolomide ± Irinotecan for Children With Refractory/Relapsed Neuroblastoma - BEACON-Neuroblastoma Trial
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:
Read more
- 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.
Read the detailed 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 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).
- Conditions
- Neuroblastoma
- Being tested
- Bevacizumab, Temozolomide, Irinotecan, Topotecan, Dinutuximab Beta
- Keywords
- Children, Young adults
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
10mg/kg IV (in the vein) on Days 1 and 15 of a 4 week cycle, for 6 cycles or until progression
TemozolomideDrug
Also called Temodal
200mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression
TemozolomideDrug
Also called Temodal
100mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 3 week cycle, for 6 cycles or until progression
IrinotecanDrug
Also called Campto
50mg/m2/d IV (in the vein) on Days 1 to 5 of a 3 week cycle, for 6 cycles or until progression
BevacizumabDrug
Also called Avastin
15mg/kg IV (in the vein) on Day 1 of a 3 week cycle, for 6 cycles or until progression
TopotecanDrug
0.75mg/m2/d IV (in the vein) on Days 1-5 of a 4 week cycle, for 6 cycles or until progression
TemozolomideDrug
Also called Temodal
150mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression
Dinutuximab BetaDrug
Also called Qarziba
10mg/m2/d IV (in the vein) on Days 1 to 7 of a 4 week cycle, for 6 cycles or until progression
CyclophosphamideDrug
250mg/m2/d IV (in the vein) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression
| Study group | Role | What they receive |
|---|---|---|
| Temozolomide | Active comparator | Temozolomide Days 1-5 every 4 weeks Receives: Drug: Temozolomide |
| Bevacizumab + Temozolomide | Experimental | Bevacizumab Day 1 and 15 + Temozolomide Days 1-5 every 4 weeks Receives: Drug: Bevacizumab; Drug: Temozolomide |
| Irinotecan + Temozolomide | Experimental | Irinotecan Days 1-5 + Temozolomide Days 1-5 every 3 weeks Receives: Drug: Temozolomide; Drug: Irinotecan |
| Bevacizumab + Irinotecan + Temozolomide | Experimental | Bevacizumab Day 1 + Irinotecan Days 1-5 + Temozolomide Days 1-5 every 3 weeks Receives: Drug: Temozolomide; Drug: Irinotecan; Drug: Bevacizumab |
| Temozolomide + Topotecan | Experimental | Temozolomide Days 1-5+ Topotecan Days 1-5 every 4 weeks Receives: Drug: Topotecan; Drug: Temozolomide |
| Bevacizumab + Temozolomide + Topotecan | Experimental | Bevacizumab Day 1 and 15 + Temozolomide Days 1-5 + Topotecan Days 1-5 every 4 weeks Receives: Drug: Bevacizumab; Drug: Topotecan; Drug: Temozolomide |
| Dinutuximab beta + Temozolomide | Experimental | Dinutuximab beta Days 1-7 + Temozolomide Days 1-5 every 4 weeks Receives: Drug: Temozolomide; Drug: Dinutuximab Beta |
| Dinutuximab beta + Temozolomide + Topotecan | Experimental | Dinutuximab beta Days 1-7 + Temozolomide Days 1-5 + Topotecan Days 1-5 every 4 weeks Receives: Drug: Temozolomide; Drug: Topotecan; Drug: Dinutuximab Beta |
| Dinutuximab beta + Topotecan + Cyclophosphamide | Other | Dinutuximab beta Days 1-7 + Topotecan Days 1-5 + Cyclophosphamide Days 1-5 every 4 weeks Receives: Drug: Topotecan; Drug: Dinutuximab Beta; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: Assessment will be after 30 days after treatment or end of trial
Secondary outcomes (4)
To evaluate the toxicity of the regimens
Safety of the regimens: Incidence and severity of Adverse Events (AE)s
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Assessment will be after 30 days after treatment or end of trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2014 (estimated)
- Study startJul 2013
- Primary completion1 Aug 2021
- Study completion18 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 225 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK, Roche Pharma AG, Imagine for Margo, EUSA Pharma, Inc.
- Responsible party
- Sponsor
- Investigators
- Lucas Moreno, MD, Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02308527
- Sponsor's protocol ID
- RG_11-087
- Other IDs
- 2012-000072-42
- Acronym
- BEACON
- Status last verified
- Apr 2026
- First submitted
- 10 Sep 2014
- Last updated
- 12 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Moreno L, Weston R, Owens C, Valteau-Couanet D, Gambart M, Castel V, Zwaan CM, Nysom K, Gerber N, Castellano A, Laureys G, Ladenstein R, Rossler J, Makin G, Murphy D, Morland B, Vaidya S, Thebaud E, van Eijkelenburg N, Tweddle DA, Barone G, Tandonnet J, Corradini N, Chastagner P, Paillard C, Bautista FJ, Gallego Melcon S, De Wilde B, Marshall L, Gray J, Burchill SA, Schleiermacher G, Chesler L, Peet A, Leach MO, McHugh K, Hayes R, Jerome N, Caron H, Laidler J, Fenwick N, Holt G, Moroz V, Kearns P, Gates S, Pearson ADJ, Wheatley K; Innovative Therapies for Children with Cancer (ITCC) and European Association for Neuroblastoma Research (SIOPEN). Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial. J Clin Oncol. 2024 Apr 1;42(10):1135-1145. doi: 10.1200/JCO.23.00458. Epub 2024 Jan 8.
PubMed 38190578
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Phase IIb Trial of Bevacizumab Added to Temozolomide ± Irinotecan for Children With Refractory/Relapsed Neuroblastoma - BEACON-Neuroblastoma Trial
- ClinicalTrials.gov ID
- NCT02308527
- Acronym / sponsor ID
- BEACON / RG_11-087
- Conditions
- Neuroblastoma
- Keywords
- Children, Young adults
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 225 participants (actual)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- Cancer Research UK, Roche Pharma AG, Imagine for Margo, EUSA Pharma, Inc.
- Study start
- Jul 2013 (actual)
- Primary completion
- 1 Aug 2021 (actual)
- Study completion
- 18 Feb 2026 (actual)
- First posted
- 4 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Temozolomide | Active comparator | Drug: TemozolomideTemozolomide Days 1-5 every 4 weeks |
| Bevacizumab + Temozolomide | Experimental | Drug: Bevacizumab, Drug: TemozolomideBevacizumab Day 1 and 15 + Temozolomide Days 1-5 every 4 weeks |
| Irinotecan + Temozolomide | Experimental | Drug: Temozolomide, Drug: IrinotecanIrinotecan Days 1-5 + Temozolomide Days 1-5 every 3 weeks |
| Bevacizumab + Irinotecan + Temozolomide | Experimental | Drug: Temozolomide, Drug: Irinotecan, Drug: BevacizumabBevacizumab Day 1 + Irinotecan Days 1-5 + Temozolomide Days 1-5 every 3 weeks |
| Temozolomide + Topotecan | Experimental | Drug: Topotecan, Drug: TemozolomideTemozolomide Days 1-5+ Topotecan Days 1-5 every 4 weeks |
| Bevacizumab + Temozolomide + Topotecan | Experimental | Drug: Bevacizumab, Drug: Topotecan, Drug: TemozolomideBevacizumab Day 1 and 15 + Temozolomide Days 1-5 + Topotecan Days 1-5 every 4 weeks |
| Dinutuximab beta + Temozolomide | Experimental | Drug: Temozolomide, Drug: Dinutuximab BetaDinutuximab beta Days 1-7 + Temozolomide Days 1-5 every 4 weeks |
| Dinutuximab beta + Temozolomide + Topotecan | Experimental | Drug: Temozolomide, Drug: Topotecan, Drug: Dinutuximab BetaDinutuximab beta Days 1-7 + Temozolomide Days 1-5 + Topotecan Days 1-5 every 4 weeks |
| Dinutuximab beta + Topotecan + Cyclophosphamide | Other | Drug: Topotecan, Drug: Dinutuximab Beta, Drug: CyclophosphamideDinutuximab beta Days 1-7 + Topotecan Days 1-5 + Cyclophosphamide Days 1-5 every 4 weeks |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (18 listed)
- Histologically proven neuroblastoma as per International Neuroblastoma Staging System (INSS) definition
- Relapsed: any relapsed or progressed high-risk neuroblastoma
- Refractory high risk disease: Lack of adequate response to frontline therapy that precludes the patient from proceeding to consolidation therapies
- Measurable disease by cross sectional imaging (RECIST) or evaluable disease
- Age ≥1 to ≤21 years
Key exclusion criteria (17 listed)
- Previous treatment with bevacizumab, temozolomide, irinotecan or any combination of these drugs
- Known hypersensitivity to: Any study drug or component of the formulation, Chinese hamster ovary products or other recombinant human or humanised antibodies, Dacarbazine
- Prior severe arterial thrombo-embolic events (e.g. cardiac ischemia, cerebral vascular accident, peripheral arterial thrombosis)
- Any ongoing arterial thrombo-embolic events
- Patient less than (at point of planned date of randomisation): 48 hours post bone marrow aspirate/trephine, 48 hours post central line insertion, Four weeks post major surgery, One week post core biopsy, Two weeks from prior chemotherapy, Six weeks from prior craniospinal radiotherapy or MIBG therapy and two weeks from radiotherapy to the tumour bed, Eight weeks from prior myeloablative therapy with haematopoietic stem cell rescue (autologous stem cell transplant), Three months from prior allogeneic stem cell transplant, 14 days or 5 half-lives (whichever occurs later) from last administration of an IMP in an IMP-trial, 6 months from presentation of lung haemorrhage/haemoptysis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: Avastin10mg/kg IV (in the vein) on Days 1 and 15 of a 4 week cycle, for 6 cycles or until progression | Drug | Bevacizumab + Temozolomide, Bevacizumab + Temozolomide + Topotecan |
| TemozolomideAlso: Temodal200mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression | Drug | Bevacizumab + Temozolomide, Dinutuximab beta + Temozolomide, Dinutuximab beta + Temozolomide + Topotecan, Temozolomide |
| TemozolomideAlso: Temodal100mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 3 week cycle, for 6 cycles or until progression | Drug | Bevacizumab + Irinotecan + Temozolomide, Irinotecan + Temozolomide |
| IrinotecanAlso: Campto50mg/m2/d IV (in the vein) on Days 1 to 5 of a 3 week cycle, for 6 cycles or until progression | Drug | Bevacizumab + Irinotecan + Temozolomide, Irinotecan + Temozolomide |
| BevacizumabAlso: Avastin15mg/kg IV (in the vein) on Day 1 of a 3 week cycle, for 6 cycles or until progression | Drug | Bevacizumab + Irinotecan + Temozolomide |
| Topotecan0.75mg/m2/d IV (in the vein) on Days 1-5 of a 4 week cycle, for 6 cycles or until progression | Drug | Bevacizumab + Temozolomide + Topotecan, Dinutuximab beta + Temozolomide + Topotecan, Dinutuximab beta + Topotecan + Cyclophosphamide, Temozolomide + Topotecan |
| TemozolomideAlso: Temodal150mg/m2/d PO (capsule taken orally) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression | Drug | Bevacizumab + Temozolomide + Topotecan, Temozolomide + Topotecan |
| Dinutuximab BetaAlso: Qarziba10mg/m2/d IV (in the vein) on Days 1 to 7 of a 4 week cycle, for 6 cycles or until progression | Drug | Dinutuximab beta + Temozolomide, Dinutuximab beta + Temozolomide + Topotecan, Dinutuximab beta + Topotecan + Cyclophosphamide |
| Cyclophosphamide250mg/m2/d IV (in the vein) on Days 1 to 5 of a 4 week cycle, for 6 cycles or until progression | Drug | Dinutuximab beta + Topotecan + Cyclophosphamide |
Primary outcome
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.
* 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)
For the bevacizumab part 2 only; Progression-free survival (PFS)
Time frame: Assessment will be after 30 days after treatment or end of trial
Progression-free survival (PFS)
4 secondary outcomes
To evaluate the toxicity of the regimens
Time frame: Assessment will be after 30 days after treatment or end of trial
To evaluate the safety of the regimens
Time frame: Assessment will be after 30 days after treatment or end of trial
To evaluate the overall safety of the regimens
Time frame: Assessment will be after 30 days after treatment or end of trial
To evaluate the safety of the regimens
Time frame: Assessment will be after 30 days after treatment or end of trial
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
- Derived from this study: PubMed 38190578Moreno L, Weston R, Owens C, Valteau-Couanet D, Gambart M, Castel V, Zwaan CM, Nysom K, Gerber N, Castellano A, Laureys G, Ladenstein R, Rossler J, Makin G, Murphy D, Morland B, Vaidya S, Thebaud E, van Eijkelenburg N, Tweddle DA, Barone G, Tandonnet J, Corradini N, Chastagner P, Paillard C, Bautista FJ, Gallego Melcon S, De Wilde B, Marshall L, Gray J, Burchill SA, Schleiermacher G, Chesler L, Peet A, Leach MO, McHugh K, Hayes R, Jerome N, Caron H, Laidler J, Fenwick N, Holt G, Moroz V, Kearns P, Gates S, Pearson ADJ, Wheatley K; Innovative Therapies for Children with Cancer (ITCC) and European Association for Neuroblastoma Research (SIOPEN). Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial. J Clin Oncol. 2024 Apr 1;42(10):1135-1145. doi: 10.1200/JCO.23.00458. Epub 2024 Jan 8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lucas Moreno, MD principal investigator
University of Birmingham
10 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab, Temozolomide and Irinotecan in people with Neuroblastoma, run by University of Birmingham at 10 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Austria, Belgium, Denmark, France, Ireland and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02308527, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026.