Somatostatin Receptor Positive, NETs, Lymphoma, Solid Tumor, CNS Tumors, Rhabdomyosarcoma, Peripheral Primitive Neuroectodermal Tumor, GIST
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, Childhood
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.
Interventions
DRUGLutetium 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
OTHERAmino 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.
Sponsors
ITM Solucin GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
24 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
Key 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. Key
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pediatric Dosage | 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 | Pediatric dosage based on: 1. absorbed dose by target organs (kidney and bone marrow). 2. rate of Dose limitting toxicities - based on adverse event reporting. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | At the end of Cycle 2 (each cycle is 28 days) | Assess preliminary anti-tumor activity by tumor type |
| PK and dosimetry | Dosimetry assessments will be performed at multiple timepoints at Cycle 1, 2 and 4. | Lutetium Lu 177 edotreotide PK evaluation and tumor and target organ dosimetry |
| Rate of adverse events | 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.. | Safety evaluation of Lutetium Lu 177 edotreotide targeted RPT as monotherapy or following standard of care |
| Overall Survival, Progression-Free Survival and Duration of Response | Every 9 ± 3 weeks from enrollment until disease progression or for up to two years, whichever came first. | Additional preliminary efficacy evaluation of lutetium Lu 177 Edotreotide targeted RPT as monotherapy or following SoC |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Endpoint: Quality of Life | At enrollment, 18 days prior to cycles 2-6, four ± 3 weeks after targeted RPT. | Assess quality of life based on the adapted Quality of Life (QoL) scale (PedsQL TM 3.0 Cancer Module) |
| Exploratory Endpoint: Correlation between SSTR expression detected by immunohisto-chemistry and functional imaging | No timeframe given. | Correlation of the expression level of SSTR immunohistochemistry in tumor biopsy or surgery samples and 111In-based, 99mTc-based, or 68Ga-based-based lesion uptake (regarding intensity/distribution) |
Countries
Spain, United States
Contacts
Primary ContactShahanaz Rahman
Backup ContactSerhii Melnyk, MD
Outcome results
None listed