Clinical trial NCT06441331: Phase I Trial to Determine the Dose and Evaluate the PK of Lutetium Lu 177 Edotreotide Therapy in Pediatric Participants With SSTR-positive Tumors
Official title: A Multicenter, Open-label, Interventional Phase I Trial to Determine the Dose and Evaluate the Pharmacokinetics (PK) and Safety of Lutetium Lu 177 Edotreotide Targeted Radiopharmaceutical Therapy (RPT) as Monotherapy or Following Standard of Care (SoC) for the Treatment of Somatostatin Receptor-positive Tumors in the Pediatric Population (KinLET).
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: NET
Lymphoma
Solid Tumor, Childhood
Somatostatin Receptor Positive
CNS Tumor
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
Lead sponsor: ITM Solucin GmbH
Sponsor class: INDUSTRY
First posted: 2024-06-04
Enrollment: 20
Sex: ALL
Minimum age (years): 24
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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

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.

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.

Primary outcomes:
measure: Progression-Free Survival
timeFrame: 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.
Secondary outcomes:
measure: Objective Response Rate
timeFrame: At the end of Cycle 2 (each cycle is 28 days)
Other outcomes:
measure: Rate of adverse events
timeFrame: From treatment start until 4 weeks after End of Last Treatment.
measure: Overall Survival, Progression-Free Survival and Duration of Response
timeFrame: Every 9 ± 3 weeks from enrollment until disease progression or for up to two years, whichever came first.
Locations:
Study officials:
affiliation: Director Clinical Operations and Alliance Management
name: Nicolas Schneider, PhD
role: STUDY_DIRECTOR
References: