Study to evaluate safety and dosimetry of Lutathera in adolescent patients with GEP-NETs and PPGLs.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Advanced Accelerator Applications

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Apr 2021 → ongoing

Decision date (initial)

2024-07-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Advanced Accelerator Applications

External identifiers

EU CT number

2023-507444-37-00

EudraCT number

2020-002951-39

ClinicalTrials.gov

NCT04711135

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Safety

- To evaluate organ absorbed radiation doses from PRRT with Lutathera in adolescent patients with SSTR-positive GEP-NETs and PPGLs as a pooled cohort
- To evaluate safety and tolerability of Lutathera in adolescents with SSTR-positive GEP-NETs and PPGLs as a pooled cohort

Secondary objectives 3

1. To evaluate cumulative safety of Lutathera in adolescents with SSTR-positive GEP-NETs and PPGLs as a pooled cohort
2. To evaluate long-term safety of Lutathera in adolescents with SSTR-positive GEP-NETs and PPGLs as a pooled cohort
3. To perform comparative assessment of dosimetry and pharmacokinetics (PK) between adolescent patients with GEP-NET and PPGLs as a pooled cohort and adult patients using the extrapolation model developed for the clinical study

Conditions and MedDRA coding

somatostatin receptor positive gastroenteropancreatic neuroendocrine (GEP-NET) tumors, pheochromocytoma and paragangliomas

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-002950-PIP01-20

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. GEP-NET cohort: presence of metastasized or locally advanced, inoperable (curative intent), histologically proven, G1 or G2 (Ki-67 index ≤20%), well differentiated GEP-NET. PPGL cohort: presence of metastasized or locally advanced, inoperable (curative intent), histologically proven PPGL.
2. Patients from 12 to < 18 years of age at the time of enrollment.
3. Expression of somatostatin receptors confirmed by a somatostatin receptor imaging (SRI) modality within 3 months prior to enrollment, with tumor uptake observed in the target lesions more or equal to the normal liver uptake.
4. Performance status as determined by Karnofsky score ≥ 50 or Lansky Play-Performance Scale score ≥ 50.
5. Parent’s ability to understand and the willingness to sign a written informed consent document for adolescents as determined by local regulations. Adolescents will sign assent along with parental/legal guardian consent or will co-sign consent with parent/legal guardian in accordance with local regulation, prior to participation in the study.

Exclusion criteria 13

1. Laboratory parameters: • Estimated creatinine clearance calculated by the Cockroft-Gault method < 70 mL/min • Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L; platelets <75x109/L. • Total bilirubin >3 x ULN for age. • Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
2. Established or suspected pregnancy
3. Breastfeeding female patients unless they accept to discontinue breastfeeding from the 1st dose until 3 months after the last administration of study drug.
4. Female patients of child-bearing potential (female pediatric patients who are menarchal or who become menarchal during the study), unless they are using highly effective methods of contraception during treatment and for 7 months after the last dose of Lutathera (see details in the Appendix 1). If local regulations deviate from the listed contraception methods to prevent pregnancy, local regulations apply and will be described in the ICF.
5. Sexually active male patients, unless they agree to remain abstinent (refrain from heterosexual intercourse) or be willing to use condoms and highly effective methods of contraception with female partners of childbearing potential, and to use condoms with pregnant female partners during the treatment period and for at least 4 months after the last dose of Lutathera (see details in Appendix 1). In addition, male patients must refrain from donating sperm during this same period.
6. Patients for whom in the opinion of the investigator other therapeutic options are considered more appropriate than the therapy offered in the study, based on patient and disease characteristics.
7. Current spontaneous urinary incontinence.
8. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.
9. Hypersensitivity to the study drug active substance or to any of the excipients.
10. Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.
11. Patient with known incompatibility to CT scans with I.V. contrast due to allergic reaction or renal insufficiency. If such a patient can be imaged with MRI, then the patient would not be excluded.
12. Patients who received any investigational agent within the last 30 days.
13. Prior therapies and procedures as detailed in Section 5.2.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Target organ (e.g. kidney and bone marrow) absorbed radiation doses in adolescents with SSTR-positive GEP-NETs and PPGLs as a pooled cohort.
2. The incidence of adverse events (AEs) and laboratory toxicities after the 1st Lutathera administration in adolescents with SSTR-positive GEPNETs and PPGLs as a pooled cohort

Secondary endpoints 3

1. The incidence of adverse events (AEs) and laboratory toxicities until 6 months after the last Lutathera dose (short-term follow-up) in adolescents with SSTR-positive GEP-NETs and PPGLs as a pooled cohort.
2. The incidence of adverse events (AEs) and laboratory abnormalities during the long term follow-up of 5 years and 10 years after the last Lutathera dose in adolescents with SSTR-positive GEP-NETs and PPGLs as a pooled cohort.
3. Calculated organ absorbed doses and PK parameters based on imaging/blood radioactivity concentration data from adolescent patients with SSTR-positive GEP-NETs and PPGLs as a pooled cohort compared to the predicted distribution /organ absorbed doses

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Advanced Accelerator Applications

Sponsor organisation

Advanced Accelerator Applications

Address

8 Rue Henri Sainte Claire Deville

City

Rueil-Malmaison

Postcode

92500

Country

France

Scientific contact point

Organisation

Advanced Accelerator Applications

Contact name

Regulatory Affairs Team

Public contact point

Organisation

Advanced Accelerator Applications

Contact name

Regulatory Affairs Team

Third parties 4

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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