A randomised phase IIb trial of bevacizumab added to temozolomide ± irinotecan for children with refractory/relapsed neuroblastoma - BEACON-Neuroblastoma Trial
- Conditions
- Neuroblastoma10027655
- Registration Number
- NL-OMON50504
- Lead Sponsor
- The University of Birmingham
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 25
Disease specific• Histologically proven neuroblastoma as per International
Neuroblastoma Staging System (INSS) definition • Relapsed or refractory
neuroblastomao Relapsed: any relapsed or progressed high-risk neuroblastoma o
Refractory high risk disease: Lack of adequate response to frontline therapy
that precludes the patient from proceeding to consolidation therapies (e.g
myeloablative chemotherapy)• Measurable disease by cross sectional imaging
(RECIST) or evaluable disease (uptake on MIBG scan with or without bone marrow
histology). Patients with only bone marrow detectable disease (bone marrow
aspirate or trephine) are NOT eligible for the studyGeneral• Age >=1 to <=21
years• Informed consent from patient, parent or guardianPerformance and organ
function• Performance Status:o Lansky >= 50%, Karnofsky >= 50% or ECOG <=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• Bone
marrow function (within 72 hours of randomisation):o No bone marrow disease: *
Platelets >= 75 x 10e9/L (unsupported for 72 hours) * ANC >= 0.75 x 10e9/L (no
G-CSF support for 72 hours)* Haemoglobin >= 8 g/dL (transfusions allowed)o Bone
marrow disease: * Platelets >= 50 x109/L (unsupported for 72 hours) * ANC >=0.5
x 10e9/L (no G-CSF for 72 hours)* Haemaglobin >= 8 g/dL (transfusions allowed) •
Renal function (within 7 days of randomisation):o Serum creatinine <=1.5 ULN for
age, if higher, a calculated GFR (radioisotope or 24 hour urine calculated
creatinine clearance) must be >= 60 ml/min/1.73 m2 • Liver function (within 72
hours of randomisation): AST and ALT <=3 ULN and total bilirubin <=1.5 ULN. In
case of liver metastases, AST and ALT <=5 ULN and total bilirubin <=2.5 ULN•
Cardiac function measured by echocardiogram within 4 weeks of randomization or
within 12 weeks if the patient has not received anthracyclines or cardiotoxics
in between, shortening fraction >=29% on echocardiogram • • Adequate lung
function: no dyspnea at rest and pulse oximetry > 94% in room air
• Females of childbearing potential must have a negative serum or urine
pregnancy test within 72 hours prior to initiation of treatment. Sexually
active women of childbearing potential must agree to use acceptable and
appropriate contraception during the study and for at least 6 months after the
last study treatment administration. Sexually active male patients must agree
to use condoms during the study for at least 6 months after the last study
treatment administration.
• 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
(neuronen, perifere pijn vezels, huid) aanwezig is. Dinut
• Previous treatment with temozolomide
• Previous treatment with chemotherapy in combination with anti-GD2 directed
therapy (*chemo immunotherapy*) with any anti-GD2 antibody. Prior treatment
with anti-GD2 directed therapy alone with/without cytokines is allowed provided
a 4 week wash-out period is met
• Known hypersensitivity to:o Any study drug or component of the formulation
o Patients with mild previous hypersensitivity reactions to anti-GD2 antibodies
may be included, but those with severe (or G4) hypersensitivity reactions to
anti-GD2 antibodies will be excluded• Clinically significant neurological
deficit, uncontrolled seizures or objective peripheral neuropathy ( >grade 2).
(Unresolved neurological deficits from spinal cord compression are acceptable)
• Uncontrolled infection
• Inadequate recovery from prior surgery with no ongoing >= grade 3 surgical
complications. For core biopsies, no less than 24 hours; for open excisional
biopsies, no less than 48 hours; for major surgery , no less than 2 weeks•
Patient less than (at point of planned date of randomisation):o Two weeks from
prior chemotherapy. One week from prior oral metronomic chemotherapy (i.e. oral
etoposide or oral cyclophosphamide)o Six weeks from prior craniospinal
radiotherapy or MIBG therapy and two weeks from radiotherapy to the tumour bed.
No washout is required for palliative radiotherapyo Eight weeks from prior high
dose chemotherapy with autologous haempoietic stem cell rescue o Three months
from prior allogeneic stem cell transplant, no ongoing treatment with
immunosuppressive agents and no signs of >=grade 2 acute graft versus host
diseaseo 14 days or 5 half-lives (whichever occurs later) from last
administration of an IMP in an IMP-trialo 14 days or 5 half-lives (whichever
occurs later) from last administration of any other biological/targeted
anticancer agent• Bleeding metastases (Patients with CNS metastases can be
enrolled as long as the metastases are not bleeding)• Pregnant or lactating
patient• Any uncontrolled medical condition that poses an additional risk to
the patient • Low probability of treatment compliancet geen anthracyclines of
cardi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>- Best response (Complete Response [CR], or Partial Response [PR][1] at any<br /><br>time during the first 6 cycles of trial treatment</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>- Safety of the regimens: Incidence and severity of Adverse Events (AE)s<br /><br>- Progression-free survival (PFS)<br /><br>- Event-free survival (EFS)<br /><br>- Overall survival (OS)<br /><br><br /><br><br /><br>Exploratory/Tertiary Endpoints:<br /><br>- Changes in magnetic resonance imaging (MRI) derived functional imaging<br /><br>biomarkers of angiogenesis: this will not take place in the NL due to lack of<br /><br>financing<br /><br>- Changes in circulating mRNA levels for TH, PHOX2B and DCX in bone marrow and<br /><br>blood samples<br /><br>- Pharmacokinetics of bevacizumab</p><br>