Phase I Trial to Determine the Dose and Evaluate the PK of Lutetium Lu 177 Edotreotide Therapy in Pediatric Participants With SSTR-positive Tumors

Phase 1

Not yet recruiting

• Conditions: NET; Lymphoma; Solid Tumor, Childhood; Somatostatin Receptor Positive; CNS Tumor
• Interventions: Drug: Lutetium Lu 177-Edotreotide; Other: Amino Acid Solution

• Registration Number: NCT06441331
• Lead Sponsor: ITM Solucin GmbH

Brief Summary

The purpose of the study is to determine the appropriate pediatric dosage and evaluate the pharmacokinetics (PK) and safety of Lutetium Lu 177 Edotreotide Targeted Radiopharmaceutical Therapy (RPT) as a monotherapy or following standard of care (SoC) in participants ≥2 to \<18 years of age with somatostatin receptor (SSTR)-positive tumors.

Detailed Description

Determine the dose, pharmacokinetics and safety of Lutetium Lu 177 Edotreotide as monotherapy or following sequential standard of care in pediatric participants with recurrent, progressive or refractory NET, CNS, lymphoma and other solid tumors that express SSTRs by immunohistochemistry and demonstrate uptake by somatostatin receptor imaging. Lutetium Lu 177 Edotreotide will be given intravenously once every 8 weeks for a total of up to 6 doses over an average of 48 weeks in participants aged 2-18 years.

Study Timeline

• Study First Submitted: 2024-05-22
• Study First Submitted QC: 2024-05-28
• Study First Posted: 2024-06-04
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-27
• Last Update Posted: 2024-12-02
• Study Start: 2025-01
• Primary Completion: 2028-06
• Study Completion: 2034-04

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Participants aged ≥ 24 months and < 18 years
• Confirmed diagnosis somatostatin receptor-positive (SSTR-positive) disease.
• Tumor which is relapsed or is refractory to at least one line of previous therapy
• Positive SSTR protein expression confirmed by immunohistochemistry of a tumor histology sample
• Radioactivity uptake within the primary tumor or metastatic tumor sites measured by locally available SRIs ( 111In-based, 99mTc-based, or 68Ga-based SSTR single-photon emission computed tomography (SPECT)/ computed tomography (CT) or positron emission tomography (PET)/CT imaging, which is higher than the liver uptake)
• 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 treatment modality prior to entering this trial
• In case of sequential treatment followed by SoC or prior therapy, washout period applies before starting targeted RPT

Screening Consent Participant/legal guardian is willing to sign a screening consent. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.

Exclusion Criteria

• Known hypersensitivity to Lutetium Lu 177 Edotreotide, DOTA/Edotreotide, or excipients
• Previous history of acute leukemia unless in remission for at least two years
• Extensive bone/bone marrow involvement as per Investigator's judgement unless peripheral blood stem cells (PBSC) are available at a minimum of 2.5x106 CD34+ cells/kg
• Patients who have received previous systemic targeted RPT
• Previous treatment with metaiodobenzyl guanidine (MIBG) if the predicted overall exposure is expected to exceed 2 Gy (gray) to the bone marrow or 23 Gy to the kidney.
• Previous treatment with external beam radiation therapy (EBRT) if the predicted overall exposure is expected to exceed more than 2 Gy to the bone marrow or 23 Gy to the kidney.
• Previous treatment with oncologic immune vaccine or CAR-T cell therapy
• Bulky disease in the CNS
• Presence of severe renal, hepatic, electrolyte, cardiovascular, or hematological dysfunction
• Participants who have received a live-attenuated vaccine up to four weeks prior to enrolment
• Pregnant or breastfeeding women.
• Other known malignancies.
• Serious non-malignant disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Three sequential age cohorts	Amino Acid Solution	Arms are based upon age at enrollment. The opening of the 2nd and 3rd cohort will depend on the recruitment of at least four participants with dosimetry and safety data for cycle 1, in the previous cohort. 1. ≥ 12 to \< 18 years old 2. ≥ 6 years to \< 12 years old 3. ≥ 2 to \< 6 years old
Three sequential age cohorts	Lutetium Lu 177-Edotreotide	Arms are based upon age at enrollment. The opening of the 2nd and 3rd cohort will depend on the recruitment of at least four participants with dosimetry and safety data for cycle 1, in the previous cohort. 1. ≥ 12 to \< 18 years old 2. ≥ 6 years to \< 12 years old 3. ≥ 2 to \< 6 years old

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival	Morphological/functional imaging (9 ± 3 weeks of 1st RPT,repeated 9 ± 3 weeks up to 2 years after End of Last Treatment Visit, or disease progression. Progression-Free Survival Follow Up is discontinued, then simple Follow-up for five years.	Progression-Free Survival is monitored by anatomical/functional imaging.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate	At the end of Cycle 2 (each cycle is 28 days)	Assess preliminary anti-tumor activity by tumor type