Last updated on July 2019

Activity Study of Bevacizumab With Temozolomide Irinotecan for Neuroblastoma in Children

Are you eligible to participate in this study?

You may be eligible for this study if you meet the following criteria:

  • Conditions: Neuroblastoma
  • Age: Between 1 - 21 Years
  • Gender: Male or Female

Inclusion Criteria

  • 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
  • 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 7.5 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 7.5 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

Exclusion Criteria:

  • 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
  • Prior severe arterial thrombo-embolic events (e.g. cardiac ischemia, cerebral vascular accident, peripheral arterial thrombosis)
  • Any ongoing arterial thrombo-embolic events
  • Patient <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 or meta-iodobenzylguanidine (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, <Two weeks from last administration of an investigational medicinal product (IMP) in an IMP-trial
  • Bleeding metastases
  • Invasion of major blood vessels
  • Use of enzyme inducing anticonvulsants within 72 hours of eligibility assessment
  • 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
  • Pregnant or lactating patient
  • Any uncontrolled medical condition that poses an additional risk to the patient
  • Low probability of treatment compliance
  • Planned immunisation with live vaccine

Recruitment Status: Open

Brief Description Eligibility Contact Research Team

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