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Label indication Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. Xofigo is an alpha particle-emitting radioactive therapeutic agent indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. ( 1 ) FDA label
Also known as Xofigo
Radium Chloride Ra-223 · 1 trial · 2 indications
Progression will be evaluated by the established international standards of the Prostate Cancer Working Group version 3 (PCWG3) and for soft tissue metastases (e.g. lung, liver and lymph nodes) according to the Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1).
Time to development of castration-resistance, as defined by EAU guidelines (biochemical progression or radiologic progression)
| Arm | Type | Description |
|---|---|---|
| Control: Standard Care | ACTIVE_COMPARATOR | Randomization between assignment to the control arm or the biomarker driven arm will be stratified on biomarker signatures, previous treatment, and fraction of ctDNA and will therefore occur after the results from the ctDNA profiling is obtained. Patients in the control arm will receive standard of care following national guidelines. |
| Treatment 1 in mHSPC: AR signalling inhibitors (ARSi) | EXPERIMENTAL | Assignments to therapy in the biomarker driven arms will be done on the basis of the biomarker signature using the current information about the efficacy of the various regimens for that signature. Information from previous studies may be incorporated in the randomization at study onset if such reliable data exists. Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi. |
| Treatment 2 in mHSPC: taxane-based chemotherapy in combination with ARSi | EXPERIMENTAL | Patients with TP53 mutations and TMPRSS2-ERG gene fusions will have an increased chance of being randomised to treatment with chemotherapy plus an ARSi. |
| Treatment 3 in mHSPC: Poly ADP Ribose Polymerase (PARP) inhibitor | EXPERIMENTAL | DNA-repair deficient patients will have an increased chance of receiving PARP inhibitors at study onset. |
| Treatment 1 in mCRPC: AR signalling inhibitors (ARSi) | EXPERIMENTAL | Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi. |
| Treatment 2 in mCRPC: Poly ADP Ribose Polymerase (PARP) inhibitor | EXPERIMENTAL | DNA-repair deficient patients will have an increased chance of receiving PARP inhibitors at study onset. |
| Treatment 3 in mCRPC: selective AKT Inhibitor | EXPERIMENTAL | Patients with alterations in the PI3K pathway will have an increased chance of receiving the combination treatment with Capivasertib plus Docetaxel. |
| Treatment 4 in mCRPC: Carboplatin | EXPERIMENTAL | Only patients with DNA-repair deficiency will be treated with Carboplatin as second line treatment in the castration-resistant phase of ProBio. |
| Name | Type | Description |
|---|---|---|
| Enzalutamide Oral Capsule | DRUG | Detailed conditions for the use of the study treatments including dose and dosages are described in accordance with the marketing authorization in the SmPC (Summary of Product Characteristics). |
| Abiraterone Oral Tablet | DRUG | Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC. |
| Carboplatin | DRUG | Carboplatin will be administered every 3rd week with an AUC (area under curve) = 5 with a dose calculated according to the Carboplatin AUC Dose calculation (Calvert formula):Dose (mg) = TargetAUC (mg/ml x min) x \[GFR ml/min + 25\]. |
| Cabazitaxel 60 mg Solution for Injection | DRUG | Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC. |
| Docetaxel Injectable Solution | DRUG | Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC. |
| Radium Chloride Ra-223 | DRUG | Detailed conditions for the use of the study treatment including dose and dosages are described in accordance with the marketing authorisation in the SmPC. |
| Niraparib plus Abiraterone acetate plus Prednisone | DRUG | Niraparib and Abiraterone acetate will be provided by Janssen and will be provided either as a fixed dose combination or as single agents. Detailed use of the study treatment including dose and dosages are described in the Investigator's brochures and SmPC. |
| Capivasertib plus Docetaxel | DRUG | Capivasertib is provided by AstraZeneca and will be given in combination with Docetaxel. All subjects will be given up to ten 21-day docetaxel cycles. All subjects will receive Capivasertib, which will be administered as tablets taken twice a day orally, on a 4 days on/3 days off continuous schedule, commencing cycle one, day 2, until disease progression. |
| Apalutamide | DRUG | Detailed conditions for the use of the study treatments including dose and dosages are described in accordance with the marketing authorization in the SmPC (Summary of Product Characteristics). |
| Darolutamide | DRUG | Detailed conditions for the use of the study treatments including dose and dosages are described in accordance with the marketing authorization in the SmPC (Summary of Product Characteristics). |
Inclusion Criteria: * Man with histologically confirmed prostate adenocarcinoma, initiating systemic therapy for metastatic disease, encompassing newly diagnosed (i.e. de novo) hormone sensitive prostate cancer (mHSPC) or first-line castration resistant prostate cancer (mCRPC) * Distant metastatic ...