A trial to determine the dose, and evaluate the safety and pharmacokinetics of lutetium Lu 177 edotreotide in children with somatostatin receptor-positive (SSTR+) tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ITM Solucin GmbH

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Neoplasms [C04]

Trial duration

24 Oct 2025 → ongoing

Decision date (initial)

2025-07-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-512831-66-00

ClinicalTrials.gov

NCT06441331

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Therapy

Determine the appropriate pediatric dosage based on the safety profile and the pharmacokinetics (PK) of lutetium Lu 177 edotreotide targeted radiopharmaceutical therapy (RPT).

Secondary objectives 4

1. Assess preliminary anti-tumor activity by tumor type
2. Safety evaluation of lutetium Lu 177 edotreotide targeted RPT as monotherapy or following standard of care (SoC).
3. Additional preliminary efficacy evaluation of lutetium Lu 177 edotreotide targeted RPT as monotherapy or following SoC
4. Lutetium Lu 177 edotreotide PK evaluation and tumor and target organ dosimetry

Conditions and MedDRA coding

Pediatric participants aged two to less than 18 years old with somatostatin receptor positive (SSTR-positive) solid tumors or lymphoma, recurrent/refractory to at least one prior line of therapy

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003245-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Confirmed diagnosis of SSTR-positive tumors including, but not limited to the following: a. Neuroendocrine tumors (NETs): i. GEP-NET ii. Pulmonary NET iii. Thymus NET iv. Breast NET v. Parathyroid NET vi. Gonadal and cervical NET vii. NET of unknown primary viii. Neuroblastoma ix. Paraganglioma x. Pheochromocytoma xi. Medullary thyroid carcinoma xii. Pituitary adenoma b. CNS Tumors: i. Meningioma ii. Medulloblastoma and other embryonal tumors iii. High grade gliomas and ependymomas iv. Low grade gliomas (gangliogliomas, dysembryoplastic neuroepithelial tumor) c. Lymphoma: i. Hodgkin lymphoma ii. Non-Hodgkin lymphoma (diffuse large B cell lymphoma, lymphoblastic lymphoma, follicular lymphoma). d. Rhabdomyosarcoma e. Peripheral primitive neuroectodermal tumors (Ewing family of sarcomas) f. Gastrointestinal stromal tumor
2. Age ≥ 24 months and < 18 years at the time of enrollment into this trial (enrollment will be opened by age groups sequentially; see trial design for more details)
3. Tumor which is relapsed or is refractory to at least one line of prior systemic antineoplastic therapy (depending on the tumor type one line of therapy may involve multimodality treatment). In cases where the participant has experienced only one relapse, the Investigator should assess whether enrolling the participant in the clinical trial or pursuing an existing second-line treatment would be the most appropriate course of action. Investigators should carefully evaluate the potential risks and benefits of the investigational treatment compared to the available standard therapies, ensuring that the chosen approach aligns with the participant's best interests and overall treatment goals
4. Tumor progression according to Investigator judgment
5. SSTR expression confirmed by immunohistochemistry (IHC) of a tumor histology sample (biopsy or surgical sample). An existing histology report showing SSTR positivity by IHC is acceptable. SSTR IHC positive results is mandatory before moving forward with the rest of the screening assessments in particular the SSTR SPECT/CT or PET/CT imaging. No further screening evaluation should take place in case of a negative IHC result and participant should be considered not eligible for this trial; this is to limit exposure to unnecessary SSTR SPECT/CT or PET/CT or PET/MRI ionizing radiations.
6. Radioactivity uptake within the primary tumor or metastatic tumor sites measured by locally available 111In-based, 99mTc-based, or 68Ga-based SSTR SPECT/CT or PET/CT imaging or PET/MRI, which is higher than the liver uptake, and performed within 2 months prior to informed consent. (Planar images only are not accepted). If not already available, this SSTR imaging can only take place after a positive result is observed by IHC (see inclusion criterium 5 above).
7. Anatomical/functional imaging (MRI and/or CT and/or PET/CT and/or PET/MRI and/or SPECT/CT scans depending on tumor type) of the primary tumor and metastatic sites within 2 months prior to enrollment. At least one measurable lesion should be present. All target lesions and lesions considered dominant must also be SSTR-positive, based on Investigator judgement
8. Karnofsky ≥ 50% (for participants > 16 years of age), Lansky ≥ 50% (for participants ≤ 16 years of age) at the time of screening
9. Participants must have recovered from the acute treatment related toxicities (defined as ≤ Grade 1 if not defined in eligibility criteria, excluding alopecia, stable treated electrolyte abnormalities on replacement and stable treated hypothyroidism) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this trial
10. For prior therapy or sequential treatment with SoC, theprotocol defined washout periods apply before starting the targeted RPT
11. If the child has previously received anthracyclines or external beam radiation therapy (EBRT) to the chest: An ejection fraction of ≥55% based on an echocardiogram performed within 4 weeks prior to enrollment
12. Written informed consent from parent(s) and/or legal guardian(s) and written assent from participant in accordance with local regulations, prior to registration or any trial-related screening procedures

Exclusion criteria 15

1. Known hypersensitivity to lutetium Lu 177 edotreotide or any of its components (DOTA/edotreotide, lutetium-177, etc.), or excipients
2. Pregnancy or lactation
3. Female participants of childbearing potential or male participants with female partners of childbearing potential, unless: a. willing to practice full and true sexual abstinence b. or surgically/permanently sterile (bilateral tubal occlusion, hysterectomy, or vasectomy) c. or willing to practice highly effective contraception in combination with a barrier method of contraception (e.g., condom). Contraception methods that are considered highly effective are: oral or non-oral (injected or implanted) non-estrogen progesterone-based hormonal method; oral, intravaginal, or transdermal combined estrogen and progesterone-based hormonal methods; and/or intrauterine device (IUD), and/or intrauterine hormone-releasing system (IUS), and/or bilateral fallopian tubal ligation. Sexual abstinence or the contraception methods described above must be followed throughout the entire treatment period and for 7 months for female participants and for 4 months for male participants with female partners of childbearing potential, after the last treatment. d. they are female participants whose male partners have a medically successful vasectomy (provided the partner is the sole sexual partner of the female participant of childbearing potential)
4. Participants who have received a live-attenuated vaccine up to 4 weeks prior to enrollment. Live attenuated vaccines should not be administered during the trial treatment and over the next 3 months after the last treatment dose
5. Other known malignancies, unless in complete remission for at least 2 years
6. Serious non-malignant disease (e.g., psychiatric, infectious, autoimmune or metabolic), that may interfere with the objectives of the trial or with the safety or compliance of the participant, as judged by the Investigator
7. Previous history of acute leukemia unless in remission for at least 2 years
8. Extensive bone/bone marrow involvement as per Investigator's judgement unless peripheral blood stem cells (PBSC) are available at a minimum of 2.5 x 10^6 CD34+ cells/kg (optimally 4 x 10^6 CD34+ cells/kg) for each trial participant prior to enrollment
9. Participants who have received previous systemic targeted RPT, including lutetium Lu-177 edotreotide, yttrium Y 90 edotreotide, lutetium Lu177 oxodotreotide, high-dose indium In 111 pentetreotide or other targeted RPT agents targeting SSTRs
10. Previous treatment with metaiodobenzylguanidine (MIBG) if the predicted overall absorbed doseis expected to exceed 2 Gy to the bone marrow or 23 Gy to the kidney. If a participant received a lower cumulative absorbed dose of these critical organs, he/she may participate for a number of cycles (at least 2) until this dose is reached
11. Previous treatment with EBRT, if the predicted overall absorbed dose is expected to exceed more than 2 Gy to the bone marrow or 23 Gy to the kidney. If a participant received a lower cumulative absorbed dose of these critical organs, he/she may participate for a number of cycles (at least 2) until this dose is reached.
12. Previous treatment with oncologic immune vaccine or CAR-T cell therapy
13. Bulky disease in the CNS defined as: a. Any signs of intracranial hypertension, e.g., papilledema b. Tumor with evidence of clinically significant mass effect in the brain or spine, e.g., uncal herniation or midline shift c. Tumor with diameter of > 5 cm in one dimension on T2/FLAIR d. Participants with metastatic or multi-focal disease, in case that the sites of disease meet above criteria for bulky CNS disease
14. Presence of severe renal, hepatic, electrolyte, cardiovascular, or hematological dysfunction, potentially interfering with the safety of the trial treatments, defined as followed and assessed within 7 days prior to enrollment: a. Renal: i. Estimated glomerular filtration rate eGFR < 60 mL/minute/1.73 m2 assessed by a recognized method, such as cystatin C performed within 4 weeks prior to enrollment ii. Renal tract obstruction. b. Hepatic: i. Hyperbilirubinemia > Grade 1 (NCI-CTCAE version 5.0) ii. Hypoalbuminemia > Grade 1 (NCI-CTCAE version 5.0), unless prothrombin time is within normal range. iii. Elevation of AST/ALT > Grade 1, or > Grade 2 in the presence of liver metastasis and elevation of gamma-glutamyl transferase (GGT/ ALP > Grade 2 (NCI-CTCAE version 5.0). iv. Known ascites c. Cardiovascular: i. Heart failure (New York Heart Association (NYHA) classification III and IV) ii. Uncontrolled hypertension iii. Hyperkalemia > 6.0 mmol/L which is not corrected iv. QTc interval >450 ms for males and >460 ms for females aged 12 to 18 years, or QTc interval >450 ms for any participant under 12 years of age (Rautaharju, Surawicz, and Gettes 2009) d. Hematopoietic: i. Platelets < 75 x 10^9 /L ii. Absolute neutrophil count (ANC) < 0.75 x 10^9 cells/L iii. Hemoglobin (Hb) concentration < 9.0 g/dL e. Any other ongoing Grade 2-4 toxicity from previous standard traditional or investigational therapies (NCI-CTCAE version 5.0) excluding alopecia, stable treated electrolyte abnormalities on replacement and stable treated hypothyroidism
15. Any psychological, familial, sociological or geographical condition that may hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the participant or legal guardian before registration in the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Determine the recommended dosage defined as the highest lutetium Lu 177 edotreotide dose which will comply with all the following criteria: 1. The median kidney absorbed dose of lutetium Lu-177 edotreotide is below 23 Gy for full treatment. 2. The median bone marrow absorbed dose is below 2 Gy for full treatment 3. Acceptable dose- limiting toxicity (DLT) profile (based on adverse event reporting) as evaluated by the safety monitoring committee (SMC).

Secondary endpoints 4

1. Objective -response rate (ORR): proportion of targeted RPT-treated participants with a complete response (CR) or partial response (PR), evaluated by the Investigator, under consideration of available guidelines for monitoring response in the different tumors involved (please see protocol for further details).
2. Rate of AEs: occurrence of AEs, severity, seriousness, AEs of special interest (AESIs), outcome, treatment/trial procedure-relatedness, action taken (including any treatment, and including any change in administration of theinvestigational medicinal product [IMP]),dose-modifying toxicity (DMT), DLT. Please see the protocol for assessments that will be performed to evaluate the safety of lutetium Lu 177 edotreotide.
3. Overall survival (OS) Progression-free survival (PFS) and duration of response (DoR) According to Investigator’s criteria, based on anatomical/functional imaging magnetic resonance imaging (MRI) and/or CT and/or positron emission tomography (PET)/CT and/or PET/MRI and/or SPECT/CT), according to the current guidelines appropriate for the applicable histology or tumor types
4. The following assessments, done in cycles 1 and 2. For cycle 4, reduced number of measurements might be performed based on cycle 1 and 2 data: 1.Full 3D SPECT/low dose CT imaging of one or multiple bed-positions (depending on the height of the participants) 2.Whole body planar imaging (fast acquisition using a gamma camera). 3.Blood radioactivity concentration measurements. Please see protocol for further details.

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ITM Solucin GmbH

Sponsor organisation

ITM Solucin GmbH

Address

Lichtenbergstrasse 1

City

Garching B. Muenchen

Postcode

85748

Country

Germany

Scientific contact point

Organisation

ITM Solucin GmbH

Contact name

General Information

Public contact point

Organisation

ITM Solucin GmbH

Contact name

General Information

Third parties 6

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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