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

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

NCT ID: NCT06441331

Condition: NET
Lymphoma
Solid Tumor, Childhood
Somatostatin Receptor Positive
CNS Tumor

Conditions: Official terms:
Neoplasms
Central Nervous System Neoplasms
Octreotide
Pharmaceutical Solutions
Edotreotide
Edotreotide lutetium LU-177

Conditions: Keywords:
Pediatric
CNS tumors
Solid tumors
Lymphoma
Somatostatin Receptor (SSTR)-positive Tumors
Lutetium Lu 177 Edotreotide
Targeted RPT
ITM
GEP-NET
Neuroendocrine tumors
Radiopharmaceutical Therapy

Study type: Interventional

Study phase: Phase 1

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: Three sequential age cohorts: 1. ≥ 12 to < 18 years old 2. ≥ 6 years to < 12 years old 3. ≥ 2 to < 6 years old A minimum of 20 participants with SSTR-positive tumors of which at least six participants will have gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A minimum of six participants will be required in each age cohort.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Lutetium Lu 177-Edotreotide
Description: lutetium Lu 177 edotreotide At least two cycles and a maximum of six cycles at eight-week (± 2 we-ek) intervals. Extrapolation from standard maximum adult dose of 100 Megabecquerel(MBq)/kg for a 75 kg adult for the first cohort. Dosing decision for the subsequent cohorts by Data Monitoring Committee (DMC), based on (at least) cycle 1 dosimetry and safety data from at least four participants of the preceding cohort. Route of administration: Intravenous (IV) infusion. Duration of treatment: 16-48 weeks
Arm group label: Three sequential age cohorts

Other name: 177Lu-edotreotide

Intervention type: Other
Intervention name: Amino Acid Solution
Description: The Amino-Acid Solution (AAS) to be used in this study will contain a mixture of lysine and arginine diluted in an electrolyte solution.
Arm group label: Three sequential age cohorts

Other name: Arginine-Lysine Solution

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.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 24 Months

Maximum age: 18 Years

Healthy volunteers: No

Start date: September 2024

Completion date: April 2034

Lead sponsor:
Agency: ITM Solucin GmbH
Agency class: Industry

Source: ITM Solucin GmbH

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06441331