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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oncopole Claudius Regaud

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Apr 2023 → 17 Apr 2026

Decision date (initial)

2024-08-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Direction Générale de l'Offre de Soins (DGOS)

External identifiers

EU CT number

2024-515552-21-00

EudraCT number

2020-002996-36

ClinicalTrials.gov

NCT03966651

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Therapy, Safety

The main objective is to determine the Maximum Tolerated Dose (MTD)
of 177Lu-DOTATATE in children with refractory or recurrent
neuroblastoma.

Secondary objectives 5

1. - To evaluate the safety and tolerability of 177Lu-DOTATATE in children with refractory or recurrent neuroblastoma.
2. - To evaluate the preliminary efficacy of 177Lu-DOTATATE.
3. Exploratory objective: The exploratory objectives are: - To study the pharmacokinetics and biodistribution of 177Lu-DOTATATE in children following intravenous injection
4. Exploratory objective: To provide dosimetry analysis set collecting and analyzing biomarkers of response to improve the prediction of biological consequences and patient outcome after 177Lu PRRT.
5. Exploratory objective: To assess predictive biological biomarkers of toxicity and efficacy.

Conditions and MedDRA coding

Recurrent or refractory neuroblastoma.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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-DOTATOC PET within 6 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. a) For dose levels 1 (80 MBq/kg) & 2 (100 MBq/kg): Age > 1 year and < 18 years at the time of enrollment into the study. b) For dose level 3 (120 MBq/kg): - If at least one patient < 2 years old has been enrolled in one of the previous dose levels (80 or 100 MBq/kg): Age > 1 year and < 18 years at the time of enrollment into the study. - If no patient < 2 years old was enrolled in one of the previous dose levels (80 or 100 MBq/kg): Age ≥ 2 years and < 18 years at the time of enrollment into the study.
6. Life expectancy greater than 3 months.
7. Adequate performance Status defined as Karnofsky or Lansky Play Performance Scale ≥ 50% (depending on patient's 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 6 weeks 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 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 7 months (for females) or 4 months (for males) after completion of study drug therapy (in accordance with CTFG guidelines).
13. Patient affiliated to a Social Health Insurance in France.

Exclusion criteria 12

1. Children with negative 68Ga-DOTATOC 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).
5. Prior extensive EBR therapy: - to more than 25% of the bone marrow; - for two kidneys : D50% (Right+ left kidneys) ≥15Gy and D30% (Right+ left kidneys) ≥ 20Gy” ; In case of a single remaining kidney (D50% ≥ 15Gy)
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 68GaDOTATOC.
9. Pre-existing clinically significant hyperkalemia not adequately corrected.
10. Participation in another study with an experimental molecule and/or procedure within 1 month prior to the first dose of experimental treatment.
11. Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study.
12. Childbearing or lactating patient.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 3

1. Safety will be evaluated using NCI CTCAE V5.0 and clinical dosimetry of the blood and kidneys.
2. Total Absorbed dose to the kidneys (considering both previous absorbed dose due to external beam irradiation and 177Lu-DOTATATE irradiation) will be defined.
3. 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 ca

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oncopole Claudius Regaud

Sponsor organisation

Oncopole Claudius Regaud

Address

1 Avenue Irene Joliot Curie

City

Toulouse

Postcode

31100

Country

France

Scientific contact point

Organisation

Oncopole Claudius Regaud

Contact name

Pr. Frédéric COURBON

Public contact point

Organisation

Oncopole Claudius Regaud

Contact name

Muriel MOUNIER

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

5 submissions — initial application plus substantial / non-substantial modifications