Prospective REgistry of Targeted RadionucLide TherapY in Patients With mCRPC (REALITY Study)

Study Overview
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Brief Summary
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This prospective registry aims to assess outcome and toxicity of targeted radionuclide therapies in patients with advanced prostate cancer in clinical routine. While the major investigated treatment modality is prostate-specific membrane antigen (PSMA)-targeted radioligand therapy, also other radionuclide therapies such as Ra223 and liver-directed radioembolization are included. The investigators believe that prospectively assessed long-term outcome data on implementation of radionuclide therapy, especially in the palliative setting of advanced mCRPC, help to better define the real benefits and risks of the respective treatment modalities for patients regarding survival and quality-of-life.

Detailed Description
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Targeted radionuclide therapy is comprised of different modalities that may be applied in advanced prostate cancer, either targeting bone metastases (mainly using Radium-223), any site of metastases with PSMA-expression (ß- / alpha-emitter labelled radioligands) or loco-regionally applying internal radiation (Yttrium-90 microspheres) to metastatic liver disease. While in Germany, each form of treatment is used in clinical routine, data is sparse regarding the real benefits and risks of respective modalities, also when used in a sequential order. As an example, patients receiving Ra223 treatment may later undergo PSMA targeted radioligand therapy, with little data available on dependent response relationships or cumulative risks. Prospective assessment of outcomes and toxicities in a radionuclide therapy registry is apparently superior over retrospective analyses of selected patient populations. The goal of the REALITY study is to gain a better understanding of the real-life clinical application of radionuclide therapies, with a focus on PSMA-targeted radioligand therapy in a high-volume treatment centre, and the impact of each treatment for patient outcome. Based on primary and secondary outcome measures the potential prediction of treatment benefit by baseline patient and tumor characteristics, and early changes of biomarkers will be of interest.

Official Title
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REALITY Study: Analysis of a Prospective REgistry to Assess Outcome and Toxicity of Targeted RadionucLide TherapY in Patients With mCRPC in Clinical Routine.

Conditions
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Prostate Cancer Metastatic, Castration Resistant Prostatic Cancer, Advanced Prostate Carcinoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form (Registry Study Inclusion Form) Inclusion Criteria for PSMA RLT: sufficient tumoral PSMA expression defined as tracer uptake markedly higher than (physiologic) uptake in healthy liver tissue. sufficient bone marrow reserve: leukocytes ≥ 2 G/L, platelets > 75 × 109/L sufficient overall patient condition: Eastern Oncology Cooperative Group (ECOG) performance status ≤ 3 Exclusion Criteria: Inability or unwillingness to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Lu177 PSMA RLT<br>Lutetium-177 prostate-specific membrane antigen (Lu177 PSMA) radioligand therapy (RLT) according to standard local protocol | |
| Ac225 PSMA RLT<br>Actinium-225 prostate-specific membrane antigen (Ac225 PSMA) radioligand therapy (RLT) according to standard local protocol | |
| Tandem Lu177 / Ac225 PSMA RLT<br>Combined Lu177 / Ac225 PSMA radioligand therapy according to standard local protocol | |
| Ra223 chloride<br>Bone-targeted Radium-223 (Ra223) radionuclide therapy in standard application | |
| Sm153 EDTMP<br>Bone-targeted Samarium-153 (Sm153) EDTMP radionuclide therapy in standard application | |
| Y90 microspheres<br>Radioembolization with yttrium-90 (Y90) microspheres, standard methodology | |
| Tb161 PSMA RLT<br>Terbium-161 prostate-specific membrane antigen (Tb161 PSMA) radioligand therapy (RLT) according to standard local protocol | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA response | Best PSA response and PSA response after 3 months from start of radionuclide therapy | up to 10 years | 
| PSA-PFS | PSA-based progression-free survival (PFS) according to PCWG3 criteria. From date of start of radionuclide therapy until documented and confirmed PSA-progression | up to 10 years | 
| OS | Overall survival. From date of start of radionuclide therapy until the date of death from any cause assessed | up to 10 years | 
| Toxicity (adverse events) | All toxicity occurring after start of radionuclide treatment will be registered according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.03). | up to 10 years | 
| Toxicity-related discontinuation of radionuclide treatment | Rate of toxicity-related discontinuation of radionuclide therapy | up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conventional imaging response | Response to radionuclide therapy based on conventional imaging according to RECIST 1.1 | up to10 years | 
| Molecular imaging response | Response to radionuclide therapy based on molecular imaging | up to 10 years | 
| Quality-of-life in patients receiving radionuclide therapy | Quality-of-life assessed from start of radionuclide treatment by EORTC QLQ-C30 questionaires | up to 10 years | 
| Pain control achieved by radionuclide therapy | Based on VAS-BPI patient questionaires from start of radionuclide treatment | up to 10 years | 
| Absorbed doses achieved by radionuclide therapy | Absorbed doses in Gy/GBq based on intra- / posttherapeutic dosimetry when available | up to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mCRPC, Radioligand Therapy, PSMA, PSMA-targeted Therapy, Radionuclide Therapy, Ra-223, Bone-targeted Radionuclide Therapy, Radioembolization, SIRT