Phase I Trial to Determine the Dose and Evaluate the PK and Safety 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).

Overview

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.

Interventions

• 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
• 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.

Primary outcome measures

• Pediatric Dosage [Time frame: a. Dosimetry assessments will be performed at multiple timepoints in cycle 1, 2 and 4. - b. Minimum of eight weeks after the first administration of Lutetium Lu 177 edotreotide]

Secondary outcome measures (4)

• Objective Response Rate [Time frame: At the end of Cycle 2 (each cycle is 28 days)]
• PK and dosimetry [Time frame: Dosimetry assessments will be performed at multiple timepoints at Cycle 1, 2 and 4.]
• Rate of adverse events [Time frame: From treatment start until 33 days following the last dose of trial treatment or until the End of Last Treatment (EOLT) visit, whichever occurs later..]
• Overall Survival, Progression-Free Survival and Duration of Response [Time frame: Every 9 ± 3 weeks from enrollment until disease progression or for up to two years, whichever came first.]

Eligibility criteria

Inclusion criteria

• Participants aged ≥ 2 years 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• UCSF Benioff Children's Hospital — San Francisco
• The Children's Hospital of Philadelphia (CHOP) — Philadelphia
• University of Texas - MD Anderson Cancer Center — Houston

Spain · 2 centers

• Hospital Universitario Vall d'Hebron - Oncología Médica — Barcelona
• Hospital General Universitario Gregorio Marañón — Madrid

France · 1 center

• Gustave Roussy Cancer Campus — Villejuif

Identifiers

NCT: NCT06441331 · ITM-1191-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗