Recurrent or refractory neuroblastoma. MedDRA version: 20.0 Level: PT Classification code 10029260 Term: Neuroblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10066595 Term: Neuroblastoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Lutathera®
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: LUTETIUM (177LU) OXODOTREOTIDE
CAS Number: 437608-50-9
Other descriptive name: 177Lu-DOTA0-Tyr3-Octreotate, lutet
Sponsors
INSTITUT CLAUDIUS REGAUD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Histologically confirmed diagnosis of neuroblastoma (patients can be included whatever the results of the 123ImIBG scan). 2.Recurrent or refractory neuroblastoma following at least two prior standard treatment regimen. 3.Positive 68Ga-DOTA PET within 4 weeks prior to day 1 dosing. Note: PET positivity is visually defined as follow: uptake should be equivalent or higher than the liver uptake for all lesions identified by conventional neuroblastoma imaging working. 4.Patient for whom no effective conventional therapy existing. 5.Age > 1 year and 12 years of age) -Lansky Play Performance Scale 50% or more (for patients 7.5 g/dL (transfusions are allowed) oIn case of bone marrow disease: Platelets = 75 x109/L (unsupported for 72 hours) ANC = 0.5 x 109/L Hemoglobin > 7.5 g/dL (transfusions are allowed) f)Renal function: oSerum creatinine =1.5 ULN for age; if higher, a calculated Glomerular Filtration Rate (GFR) (2009 Schwartz formula*) must be = 60 ml/min/1.73 m2 * eGFR (mL/min/1,73 m²) = height (cm) x 36,5 / serum creatinine (µmol/L) g)Liver function: oAST and ALT =2.5 ULN and total bilirubin =1.5 ULN. oIn case of liver metastases, AST and ALT =5 ULN and total bilirubin =2.5 ULN h)Cardiac function: Shortening fraction = 28% or ejection fraction = 55% by echocardiogram, with no clinical congestive heart failure associated. Normal pulmonary artery pressure. 11.Patient assent and patients/parent(s)/legal guardian(s) written informed consent that is consistent with French law and ICH-GCP guidelines. 12.Patients, both males and females, with reproductive potential (girls post menarche and males after 1st ejaculation) and sexually active must agree to practice effective contraceptive measures for the duration of study drug therapy and for at least 6 months after completion of study drug therapy (in accordance with CTFG guidelines). 13.Patient affiliated to a Social Health Insurance in France. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Children with negative 68Ga-DOTA PET. 2.Chemotherapy within 4 weeks prior to the start of study treatment, high dose chemotherapy with stem cell transplantation within 3 months prior to start study treatment, long acting somatostatin analogues within 30 days prior to start of study treatment, biological therapy or investigational agents within 4 weeks prior to the start of study treatment or prior to passing 5 half-lives, i.e. systemic clearance, whatever comes first. 3.Any previous molecular radiotherapy (PRRT, 131ImiBG or other). 4.External Beam Radiation (EBR) therapy within 30 days before starting study treatment. 5.Prior extensive EBR therapy: -to more than 25% of the bone marrow; -to both kidneys (except if scatter absorbed doses of < 0.5Gy to a single kidney or radiation to <50% of a single kidney). 6.Known brain metastases, unless these metastases have been treated and stabilized for at least 3 months prior to enrolment in the study. Patients with a history of brain metastases must have a head CT or MRI with contrast to document stable disease prior to enrolment in the study. 7.Other known co-existing malignancies. 8.Hypersensitivity to 177Lu-DOTATATE, amino acid solution or 68GaDOTATATE, 9.Participation in another study with an experimental molecule and/or procedure within 1 month prior to the first dose of experimental treatment. 10.Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study. 11.Childbearing or lactating patient.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective is to determine the Maximum Tolerated Dose (MTD) of 177Lu-DOTATATE in children with refractory or recurrent neuroblastoma.;Secondary Objective: The secondary objectives are: - To evaluate the safety and tolerability of 177Lu-DOTATATE in children with refractory or recurrent neuroblastoma. - To evaluate the preliminary efficacy of 177Lu-DOTATATE. ;Primary end point(s): The primary endpoint is to define the Maximum Tolerated Dose (MTD) of 177Lu-DOTATATE. DLT period will start from the first injection of 177Lu-DOTATATE until 6 weeks after 1st injection.;Timepoint(s) of evaluation of this end point: For each patient: until 6 weeks after the 1st administration of 177Lu-DOTATATE. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary end points are: • Safety will be evaluated using NCI CTCAE V5.0 and clinical dosimetry of the blood and kidneys. • Total Absorbed dose to the kidneys (considering both previous absorbed dose due to external beam irradiation and 177Lu-DOTATATE irradiation) will be defined. • Efficacy: will be evaluated using the INRC (2017), RECIST v1.1 criteria and investigator judgment. Objective Response Rate (ORR) will be defined as the number of patients with best objective response (i.e. complete response or partial response) divided by the total number of evaluable patients. Progression Free Survival (PFS) will be defined as the time from inclusion to progression or death due to any cause. Overall Survival (OS) will be defined as the time from inclusion to death due to any cause. Patients alive at the time of analysis will be censored at the last known alive date.;Timepoint(s) of evaluation of this end point: For each patient: until 5 months after the 1st administration of 177Lu-DOTATATE. | — |
Countries
France
Contacts
Public ContactCoordinating Investigator
INSTITUT CLAUDIUS REGAUD
Outcome results
None listed