Neuroblastoma
Conditions
Interventions
Study medication as described above depending on the cohort the pt is
randomized in.
Sponsors
The University of Birmingham
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: 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 = 50%, Karnofsky >= 50% or ECOG =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 = 60 ml/min/1.73 m2 • Liver function (within 72 hours of randomisation): AST and ALT =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
Exclusion criteria
Exclusion criteria: • 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: - Best response (Complete Response [CR], or Partial Response [PR][1] at any time during the first 6 cycles of trial treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: - Safety of the regimens: Incidence and severity of Adverse Events (AE)s - Progression-free survival (PFS) - Event-free survival (EFS) - Overall survival (OS) Exploratory/Tertiary Endpoints: - Changes in magnetic resonance imaging (MRI) derived functional imaging biomarkers of angiogenesis: this will not take place in the NL due to lack of financing - Changes in circulating mRNA levels for TH, PHOX2B and DCX in bone marrow and blood samples - Pharmacokinetics of bevacizumab | — |
Countries
Netherlands
Outcome results
None listed