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

Lymphoma Clinical Trial

— KinLET  

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).

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06441331
• Other study ID #: ITM-1191-01
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 2024
• Est. completion date: April 2034

Study information

• Verified date: May 2024
• Source: ITM Solucin GmbH
• Contact: Shahanaz Rahman
• Phone: 089 32989866000
• Email: info-solucin[@]itm-radiopharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: April 2034
• Est. primary completion date: June 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 24 Months to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Central Nervous System Neoplasms
• CNS Tumor
• Lymphoma
• Neoplasms
• NET
• Solid Tumor, Childhood
• Somatostatin Receptor Positive

Intervention

Drug:
• Lutetium Lu 177-Edotreotide
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

Other:
• Amino Acid Solution
The Amino-Acid Solution (AAS) to be used in this study will contain a mixture of lysine and arginine diluted in an electrolyte solution.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
ITM Solucin GmbH

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of adverse events	Safety evaluation of Lutetium Lu 177 edotreotide targeted RPT as monotherapy or following standard of care	From treatment start until 4 weeks after End of Last Treatment.
Other	Overall Survival, Progression-Free Survival and Duration of Response	Additional preliminary efficacy evaluation of lutetium Lu 177 Edotreotide targeted RPT as monotherapy or following SoC	Every 9 ± 3 weeks from enrollment until disease progression or for up to two years, whichever came first.
Primary	Progression-Free Survival	Progression-Free Survival is monitored by anatomical/functional imaging.	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	Objective Response Rate	Assess preliminary anti-tumor activity by tumor type	At the end of Cycle 2 (each cycle is 28 days)