MiNivAN: A study of new antibody treatments for children with relapsed/refractory neuroblastoma in combination with targeted radiotherapy
- Conditions
- euroblastomaMedDRA version: 20.0 Level: PT Classification code 10029260 Term: Neuroblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002221-11-GB
- Lead Sponsor
- niversity Hospital Southampton NHS Foundation Trust
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 36
•At study entry patients must be > 1 year
•Relapsed or refractory high risk neuroblastoma (as defined by INRG criteria)
•MIBG avid disease on imaging within 4 weeks to study entry.
•= 3 months since any myeloablative chemotherapy / stem cell rescue
•= 42 days since any other immunotherapy e.g. tumour vaccines. At least 3 half-lives since last dose of any monoclonal antibody therapy.
•Patients must have a performance status greater or equal 60% (Lansky Score or Karnofsky, see Appendix 1: Performance Scales)
•Estimated life expectancy = 12 weeks
•Adequate bone marrow function: ANC >1.0 x 109/L, platelets =50 x 109/L and haemoglobin > 8.0 g/dL
•Adequate renal function: serum creatinine <1.5 mg/dL or a estimated creatinine clearance or radioisotope GFR of > 60 mL/minute/1.73m2
•Adequate cardiac function: shortening fraction of = 28 % by echocardiogram
•Adequate hepatic function: ALT or AST < 5 x ULN and a total bilirubin < 1.5 x ULN
•Adequate lung function: FEV1 and FVC >60% of predicted by pulmonary function tests. Children unable to do PFTs should have no dyspnea at rest and a pulse oximetry >94% on room air
•Adequate pancreatic function: serum lipase < 1.5 x upper limit normal
•Patients may have had prior CNS metastasis at point of entry to study, but patients with mIBG avid parenchymal brain lesions will be excluded. All CNS disease must be treated and stable for at least 4 weeks prior to starting trial 131-I mIBG therapy (see section 4). Patients with extra-axial disease (e.g. skull (bone) metastasis that do not invade the dura) may be enrolled providing there is no evidence of brain oedema
•Patients must consent to the placement of a central venous line, if one has not already been placed.
•Patients must have no immediate requirements for palliative chemotherapy, radiotherapy or surgery.
•Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method to avoid pregnancy for 5 months after last dose of trial medication. Female patients who are lactating must agree to stop breast-feeding. Male patients who are sexually active must be instructed to use contraception throughout treatment and for a period of 7 months after last dose of trial medication.
•Patients with seizure disorders may be enrolled if seizures are well controlled.
•All patients and/or their parents or legal guardians must sign a written informed consent
•All institutional and national requirements for clinical trials must be met.
•Expression of PD-L1 by tumour is not a pre-requisite
•Parents or carers willing and able to comply with radiation safety measures needed for 131-I mIBG administration
•Patient must be judged capable of tolerating isolation procedures associated with 131-I-mIBG therapy
•Patients who have previously received Dinutuximab beta (CHO or SP2/0) will not be excluded unless they have had severe or life threatening toxicity necessitating withdrawal of treatment previously.
•Patients who have had previous 131-I mIBG therapy will not be e
•Patients previously treated with Nivolumab or any other PD-1 or PD-L1 targeting antibodies will be excluded from the study
•Previous allogeneic stem cell transplant or solid organ transplant
•Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
•Patients receiving systemic corticosteroids (other than physiological replacement) or other immunosuppressive agents within 14 days prior to study entry. Local steroid treatments (e.g. dermal, mucosal, inhaled) are allowed.
•Unable to maintain platelets = 50 x 109/L without transfusion
•HIV or Hepatitis B or C infection
•Patients who have had major surgery (e.g laparotomy or thoracotomy) within the past 2 weeks.
•Patients with significant intercurrent illnesses and/or any of the following:
oPatients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance.
oPatients with significant psychiatric disabilities or uncontrolled seizure disorders.
oPatients with active infections, or active peptic ulcers, unless these conditions are corrected or controlled.
oPatients with a clinically significant neurologic deficit or objective peripheral neuropathy (Grade >2) are ineligible.
oPatients with clinically significant, symptomatic, pleural effusions. Patients with uncontrolled hypertension
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method