PET/CT Imaging of Small Cell Lung Cancer Using 89Zr-DFO-SC16.56

Study Overview
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Brief Summary
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The purpose of this study is to look at how safe 89Zr-DFO-SC16.56 is, and how it is processed by the body in people with small cell lung cancer.

Official Title
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Immuno-PET Imaging of Neuroendocrine Tumors Using 89Zr-DFO-SC16.56, a DLL3-targeting Monoclonal Antibody

Conditions
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Small Cell Lung Cancer, Small Cell Lung Carcinoma

Intervention / Treatment
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* Drug: 89Zr-DFO-SC16.56
* Drug: SC16.56, Phase I, Cohort 2
* Drug: SC16.56, Phase I, Cohort 3
* Drug: SC16.56, Phase II


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed, informed consent Age 18 or more years Histologically confirmed, SCLC, (newly diagnosed or recurrent); small cell carcinoma of unknown or non-lung origin; or other types of neuroendocrine tumor OR Histologically confirmed prostate cancer, with suspected or confirmed NEPC based upon clinical assays obtained prior to the trial At least one tumor lesion on CT or MRI >/= 2 cm ° For the prostate cancer patient cohort with only bone metastases, a recent PET scan (FDG or PSMA-targeted) that shows tracer-avid osseous metastases, a recent MRI that shows new osseous metastases, or a bone scan that shows new osseous metastases. The scans should have been obtained in the last 8 weeks. ECOG performance status 0 to 2 Negative serum pregnancy test within 2 weeks of 89Zr- DFO-SC16.56 or women of child-bearing potential Adequate organ function as assessed by Absolute neutrophil count (ANC) >/= 1,500 mm^8 Hemoglobin >/= 8.0 g/dL Platelet count >/= 75,000/mm^3 Bilirubin </= 1.5 x ULN (upper limit of the norm) AST (GOT) </= 2.5 x ULN (when no liver metastases are present) AST (GOT) </= 5.0 x ULN (when liver metastases are present) ALT (GOT) </= 2.5 x ULN (when no liver metastases are present) ALT (GOT) </= 5.0 x ULN (when liver metastases are present) Creatinine </= 1.5 x ULN Available archival tumor biopsy material suitable for DLL3 IHC. Archival tissue is not required to have been collected within a specific time frame relative to imaging For the prostate cancer patient cohort, as an alternative if archival tissue is not available, patients must be willing to undergo PET/CT guided biopsy** as described in section 9.3. Patients with SCLC will be the primary study population, however patients with other types of neuroendocrine tumors may be included at the PI's discretion. Criterion is intended to demonstrate presence of imageable disease. A low-dose CT (e.g. from a PET/CT scan) may be used at PI's discretion While willingness to undergo the biopsy is required if archival tissue is not available, PET/CT guided biopsy is not a mandatory study assessment. As described in section 9.3, the guided biopsy may be waived at the discretion of the principal investigator if the DLL3 PET/CT reveals no sites of DLL3 tracer-avid tumor or if the principal investigator deems it is not in the best interest of the patient, according to best clinical judgement. Exclusion Criteria: History of anaphylactic reaction to humanize or human antibodies Pregnant or breast feeding Psychiatric illness that would interfere with compliance with the study procedures Inability to undergo PET scan due to weight limit

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Phase I<br>Up to 12 participants with tumors that are found to be >/= 50% positive for DLL3 by IHC | Drug: 89Zr-DFO-SC16.56<br>* Injection of 2 mCi of 89Zr-DFO-SC16.56 for Phase I participants. Dose for Phase II will be determined by results from Phase I.<br>Drug: SC16.56, Phase I, Cohort 2<br>* 7.5mg<br>Drug: SC16.56, Phase I, Cohort 3<br>* 22.5mg<br>|
| Phase II<br>Up to 18 participants with tumors that are found to be >/= 50% positive for DLL3 by IHC | Drug: 89Zr-DFO-SC16.56<br>* Injection of 2 mCi of 89Zr-DFO-SC16.56 for Phase I participants. Dose for Phase II will be determined by results from Phase I.<br>Drug: SC16.56, Phase II<br>* Dose for Phase II will be determined by results from Phase I.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Radiation Dosimetry of 89Zr- DFO-SC16.56 PET/CT imaging in participants | The PET and blood data are used to quantify tracer-biodistribution, measuring the amount of radioactivity present in the blood and bodily regions-of-interest | Up to 12 months | 
| Phase I: Safety of 89Zr- DFO-SC16.56 PET/CT imaging in cancer patients by evaluating toxicities | 89Zr- DFO-SC16.56 PET/CT will be considered safe if there are no possibly probably, or definitely related grade 3 or higher toxicities (except allergic reactions) among the patients enrolled in the phase I portion | up to 12 months | 
| Phase II: Correlation between tumor uptake of 89Zr- DFO-SC16.56 with expression of DLL3 | This is determined by immunohistochemistry and quantitative mass spectrometry. | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Small cell lung cancer, Small Cell Lung Carcinoma, 89Zr-DFO-SC16.56, 19-292, Memorial Sloan Kettering Cancer Center