Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
Searching Both is inclusive of interventional and observational studies.
|Eligible Ages||1 Year - 21 Years|
- - 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 ≥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+).
- - 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).
- - 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.
- - Blood pressure below 95th centile for age and sex.
- - 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.
- - 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.
- - 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) - 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.
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|University of Birmingham|
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Lucas Moreno, MD|
|Principal Investigator Affiliation||University of Birmingham|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
|Countries||Austria, Belgium, Denmark, France, Ireland, Italy, Netherlands, Spain, Switzerland, United Kingdom|
The disease, disorder, syndrome, illness, or injury that is being studied.
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.
Active Comparator: Temozolomide
Temozolomide Days 1-5 every 4 weeks
Experimental: Bevacizumab + Temozolomide
Bevacizumab Day 1 and 15 + Temozolomide Days 1-5 every 4 weeks
Experimental: Irinotecan + Temozolomide
Irinotecan Days 1-5 + Temozolomide Days 1-5 every 3 weeks
Experimental: Bevacizumab + Irinotecan + Temozolomide
Bevacizumab Day 1 + Irinotecan Days 1-5 + Temozolomide Days 1-5 every 3 weeks
Experimental: Temozolomide + Topotecan
Temozolomide Days 1-5+ Topotecan Days 1-5 every 4 weeks
Experimental: Bevacizumab + Temozolomide + Topotecan
Bevacizumab Day 1 and 15 + Temozolomide Days 1-5 + Topotecan Days 1-5 every 4 weeks
Experimental: Dinutuximab beta + Temozolomide
Dinutuximab beta Days 1-7 + Temozolomide Days 1-5 every 4 weeks
Experimental: Dinutuximab beta + Temozolomide + Topotecan
Dinutuximab beta Days 1-7 + Temozolomide Days 1-5 + Topotecan Days 1-5 every 4 weeks
Other: Dinutuximab beta + Topotecan + Cyclophosphamide
Dinutuximab beta Days 1-7 + Topotecan Days 1-5 + Cyclophosphamide Days 1-5 every 4 weeks
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
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: - 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: - 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
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.