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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Three sequential age cohorts | Experimental | Arms are based upon age at enrollment. The opening of the 2nd and 3rd cohort will depend on the recruitment of at least four participants with dosimetry and safety data for cycle 1, in the previous cohort.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lutetium Lu 177-Edotreotide | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Pediatric Dosage | Pediatric dosage based on:
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate | Assess preliminary anti-tumor activity by tumor type | At the end of Cycle 2 (each cycle is 28 days) |
| PK and dosimetry | Lutetium Lu 177 edotreotide PK evaluation and tumor and target organ dosimetry |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory Endpoint: Quality of Life | Assess quality of life based on the adapted Quality of Life (QoL) scale (PedsQL TM 3.0 Cancer Module) | At enrollment, 18 days prior to cycles 2-6, four ± 3 weeks after targeted RPT. |
| Exploratory Endpoint: Correlation between SSTR expression detected by immunohisto-chemistry and functional imaging |
Key Inclusion Criteria:
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Shahanaz Rahman | Contact | +4989 32989866000 | kinlet@itm-radiopharma.com | |
| Serhii Melnyk, MD | Contact | kinlet@itm-radiopharma.com |
| Name | Affiliation | Role |
|---|---|---|
| Roman Henkel, PhD | Director, Global Clinical Operations | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Children's Hospital of Philadelphia (CHOP) | Recruiting | Philadelphia | Pennsylvania | 19104-4319 | United States |
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Three sequential age cohorts:
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.
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| Amino Acid Solution | Other | The Amino-Acid Solution (AAS) to be used in this study will contain a mixture of lysine and arginine diluted in an electrolyte solution. |
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| Dosimetry assessments will be performed at multiple timepoints at Cycle 1, 2 and 4. |
| Rate of adverse events | Safety evaluation of Lutetium Lu 177 edotreotide targeted RPT as monotherapy or following standard of care | 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 | 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. |
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) |
| No timeframe given. |
| University of Texas - MD Anderson Cancer Center | Recruiting | Houston | Texas | 77030 | United States |
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| Gustave Roussy Cancer Campus | Recruiting | Villejuif | 94800 | France |
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| Hospital Universitario Vall d'Hebron - Oncología Médica | Recruiting | Barcelona | 08035 | Spain |
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| Hospital General Universitario Gregorio Marañón | Recruiting | Madrid | 28009 | Spain |
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| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D016543 | Central Nervous System Neoplasms |
| D012208 | Rhabdomyosarcoma |
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| C535650 | Gastro-enteropancreatic neuroendocrine tumor |
| D018358 | Neuroendocrine Tumors |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009422 | Nervous System Diseases |
| D009217 | Myosarcoma |
| D009379 | Neoplasms, Muscle Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D012509 | Sarcoma |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
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| ID | Term |
|---|---|
| C504257 | 177Lu-octreotide, DOTA(0)-Tyr(3)- |
| C545824 | amino-acid, glucose, and electrolyte solution |
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