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BEACON: A randomised phase IIb trial of BEvACizumab added to Temozolomide ± IrinOtecan for children with refractory/relapsed Neuroblastoma
EU CTIS ID: 2024-518931-12-00
What this study is testing
- 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
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Histologically proven neuroblastoma as per International Neuroblastoma Staging System (INSS) (Brodeur et al. 1988) definition
- Cardiac function, measured using echocardiogram prior to 4 weeks of randomisation date or 12 weeks if patient has not received anthracyclines or cardiotoxics. Shortening fraction ≥29% on echocardiogram
- Adequate lung function; no dyspnoea 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 males patients must agree to use condom during the study and 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
- Relapsed or refractory neuroblastoma o 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)
You likely can't join if
- Previous treatment with temozolomide drugs
- Current chronic intestinal inflammatory disease/bowel obstruction (Bevacizumab randomisation only)
- Known intolerance to galactose and fructose, lactase deficiency, and/or defect of absorption of galactose and fructose (Bevacizumab randomisation only)
- 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
See the full eligibility criteria
Who can join
- Histologically proven neuroblastoma as per International Neuroblastoma Staging System (INSS) (Brodeur et al. 1988) definition
- Cardiac function, measured using echocardiogram prior to 4 weeks of randomisation date or 12 weeks if patient has not received anthracyclines or cardiotoxics. Shortening fraction ≥29% on echocardiogram
- Adequate lung function; no dyspnoea 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 males patients must agree to use condom during the study and 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
- Relapsed or refractory neuroblastoma o 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 study
- Age ≥1 to ≤21 years
- Informed consent from patient, parent or guardian
- Performance Status: o Lansky ≥ 50%, Karnofsky ≥ 50% or ECOG ≤3 o (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)
- Bone marrow function (prior to 72 hours of planed randomisation date): o No bone marrow disease: Platelets ≥ 75 x 109/L (unsupported for 72 hours) ANC ≥ 0.75 x 109/L (no G-CSF support for 72 hours) Haemoglobin > 7.5 g/dL (transfusions allowed) o Bone marrow disease: Platelets ≥ 50 x109/L (unsupported for 72 hours) ANC ≥0.5 x 109/L (no G-CSF for 72 hours) Haemoglobin > 7.5 g/dL (transfusions allowed) Dinutuximab beta arm only: • Bone marrow function (within 72 hours of randomisation): o No bone marrow disease: Platelets ≥75 x 109/L (unsupported for 72 hours) ANC ≥ 0.75 x109/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 109/L (no G-CSF for 72 hours) Haemoglobin ≥ 8 g/dL (transfusions allowed)
- Renal function (prior to 7 days of randomisation date):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 (prior to 72 hours of randomisation date): AST or ALT ≤3 ULN and total bilirubin ≤1.5 ULN. In case of liver metastases, AST or ALT ≤5 ULN and total bilirubin ≤2.5 ULN.
What rules you out
- Previous treatment with temozolomide drugs
- Current chronic intestinal inflammatory disease/bowel obstruction (Bevacizumab randomisation only)
- Known intolerance to galactose and fructose, lactase deficiency, and/or defect of absorption of galactose and fructose (Bevacizumab randomisation only)
- 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
- 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
- Patients with mild previous hypersensitivity reactions to anti-GD2 antibodies may be included, but those with severe (or G4) hypersensitivity reactions to antiGD2 antibodies will be excluded Clinically significant neurological deficit, uncontrolled seizures or objective peripheral neuropathy (>grade 2). (Unresolved neurological deficits from previous 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): Two weeks from prior chemotherapy. One week from prior oral metronomic chemotherapy (i.e. oral etoposide or oral cyclophosphamide).Six weeks from prior craniospinal radiotherapy or MIBG therapy and two weeks from radiotherapy to the tumour bed. No washout is required for palliative radiotherapy Eight weeks from prior high dose chemotherapy with autologous haematopoietic stem cell rescue Three months from prior allogeneic stem cell transplant, no ongoing treatment with immunosuppressive agents and no signs of ≥grade 2 acute graft versus host disease 14 days or 5 half-lives (whichever occurs later) from last administration of an IMP in an IMP-trial. 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 compliance
- History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation) (Bevacizumab randomisation only)
- History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to study enrolment (Bevacizumab randomisation only)
The study team makes the final eligibility decision.
Where it's taking place
- Switzerland
- United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Switzerland; United Kingdom. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.