PSMA in Gastrointestinal Tumors (GIPSMA, Focusing on Neuroendocrine Neoplasms)

Study Overview
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Brief Summary
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The theranostic principle is based on the use of radiolabeled compounds which can be applied for diagnostic molecular imaging and targeted delivery of radiation to the tumor. Gastrointestinal tumors (GIT), including gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) also express a phenotypic biomarker called prostate-specific membrane antigen (PSMA), thereby rendering it a potential diagnostic (through positron emission tomography (PET) scan imaging) and therapeutic target for radioligand therapy. Aim is to evaluate whether PSMA-directed in-vivo imaging can be also applied to GEP-NEN patients to determine if i) biopsy-derived tissue of newly diagnosed patients exhibit a PSMA expression profile, ii) PSMA-PET shows upregulated PSMA expression in-vivo, iii) such a molecular imaging approach identifies more disease sites relative to conventional imaging, and iv) if the PSMA PET signal predicts further clinical course and outcome under guideline-compatible treatment.

Official Title
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A Molecular Imaging-Derived Biomarker of PSMA Expression - Revealing Theranostic Potential in Gastrointestinal Tumors (Focusing on Neuroendocrine Neoplasms)

Conditions
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Gastrointestinal Cancer

Intervention / Treatment
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* Radiation: 18F-PSMA PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly diagnosed GEP-NEN prior to initiation of guideline-compatible, anti-tumor therapy Available tissue specimen to conduct PSMA expression profiling Male/female, above 18 years old Patients must provide written informed consent Patients must be willing to comply with study procedures and available for follow-up examinations Exclusion Criteria: Curative setting Not sufficient tumor tissue available Male Patients: No prostate carcinoma Other malignant neoplasms in patient's history Pregnancy or Breastfeeding Contraindications for PET/CT

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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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gastrointestinal tumors histologically positive for PSMA<br>Tumor biopsy at baseline to establish diagnosis and to identify PSMA expression in an ex-vivo setting. Patients with ex-vivo PSMA expression receive a multimodal imaging approach: This includes a PSMA-targeted PET/CT (18F-PSMA) at baseline and conventional imaging. | Radiation: 18F-PSMA PET/CT<br>* Patients with metastasized gastrointestinal tumors, that exhibit histological PSMA expression, receive an additional 18F-PSMA PET/CT to routine imaging.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| True positive rate per patient specimen | The probability of GEP-NEN is given when immunhistochemistry test is positive. | 24 months | 
| True positive rate per patient | The probability of GEP-NEN is given when 18F-PSMA-1007 PET/CT is positive on a per patient basis. | 24 months | 
| Number of patients with identified tumor lesion sites | To compare the sites of disease identified on 18F-PSMA-1007 PET/CT in patients with GEP-NEN to images derived by conventional imaging to evaluate the sensitivity of 18F-PSMA-1007 PET/CT. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ex-vivo PSMA expression | Expression of PSMA per specimen at immunhistochemistry. | 24 months | 
| PSMA uptake on 18F-PSMA-1007 PET | Quantified uptake of PSMA per tumor lesion basis. | 24 months |