A Phase I Clinical Study Evaluating the Safety of Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTA0-Tyr3-Octreotate in Children with Refractory or Recurrent Neuroblastoma expressing somatostatin receptors.

Phase 1

• Conditions: Recurrent or refractory neuroblastoma.; MedDRA version: 20.0Level: PTClassification code 10029260Term: NeuroblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10066595Term: Neuroblastoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-002996-36-FR
• Lead Sponsor: INSTITUT CLAUDIUS REGAUD

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-04-26
• Last Update Posted: 8 November 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 18

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 < 18 years at the time of enrollment into the study.
6.Life expectancy greater than 3 months.
7.Adequate performance Status defined as:
-ECOG < 2 (for patients >12 years of age)
-Lansky Play Performance Scale 50% or more (for patients <12 years of age)
8.Adequate recovery from major surgery prior to receiving study treatment.
9.Patients must have recovered (to CTCAE grade 1 or baseline) from any acute toxicity resulting from any prior anti-cancer treatment (except alopecia and ototoxicity).
10.Patient must have adequate organ function as defined by the following values (within 1 week of first dose of study treatment):
e)Bone marrow function:
oIf no bone marrow disease:
Platelets = 100 x 109/L (unsupported for 72 hours)
Absolute Neutrophil Count (ANC) = 0.75 x 109/L
Hemoglobin > 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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified