Rhenium-188-HEDP vs. Radium-223-chloride in Patients With Advanced Prostate Cancer Refractory to Hormonal Therapy
Rhenium-188-HEDP vs. Radium-223-chloride in Patients With Advanced Prostate Cancer Refractory to Hormonal Therapy
Radium-223 chloride is an alpha-emitting radiopharmaceutical with proven survival benefit in
 patients with castration-resistant prostate cancer metastatic to bone. Beta-emitting
 radiopharmaceuticals have proven efficacy for palliating malignant bone pain. Nowadays,
 rhenium-188-HEDP is used in clinical practice for pain relief and palliative care. Several
 studies suggest that also rhenium-188-HEDP has the potential to improve overall survival. The
 purpose of this study is to investigate if treatment with rhenium-188-HEDP results in
 improvement of overall survival compared to treatment with radium-223-chloride.
The main objective of this trial is to compare rhenium-188-HEDP (a beta-emitting
 radiopharmaceutical) with radium-223-chloride (an alfa-emitting radiopharmaceutical), in
 patients with castration-resistant prostate cancer metastatic to bone, with overall survival
 as primary endpoint.

 For radium-223-chloride, an overall survival benefit has been proven in a large randomized
 phase III trial. Although such a trial has never been performed for rhenium-188-HEDP, some
 trials in literature suggest a survival benefit for rhenium as well.

 Rhenium has some advantages compared to radium. Firstly, it is easily available as it can be
 produced in the hospital. Secondly, the costs of rhenium are significantly lower compared to
 radium. Lastly, rhenium seems to have a favorable pain response. However, no randomized
 trials have been performed to confirm this.
Inclusion Criteria:

 -  Male, 18 years or older

 -  Histologically confirmed prostate cancer

 -  Bone metastases (≥ 6 lesions) showing pathological uptake at bone scintigraphy.

 -  WHO performance status of ≤2

 -  Life expectancy of at least 6 months

 -  Castration-resistant disease: serum testosterone level of ≤ 1.7 nmol per liter (≤50 ng
 per deciliter) after bilateral orchiectomy or during maintenance treatment consisting
 of androgen-ablation therapy with a luteinizing hormone-releasing hormone agonist.
 During study treatment the maintenance androgen-deprivation therapy must be continued.

 -  Baseline PSA ≥5 ng/ml with evidence of progressively increasing PSA values

 -  Symptomatic disease with either regular use of analgesic medication or treatment with
 external-beam radiotherapy for cancer-related bone pain within the previous 12 weeks.

 -  Progression on or after treatment with docetaxel, or inability to receive docetaxel.

 -  Adequate renal function (serum creatinine level ≤1.5 x ULN)

 -  Adequate hematological function defined as absolute neutrophil count ≥ 1.5x10^9/L and
 platelet count ≥100x 10^9/L)

 -  Written informed consent

 Exclusion Criteria:

 -  Treatment with chemotherapy within the previous 4 weeks

 -  Continuation of treatment with abiraterone or enzalutamide

 -  Previous hemibody external radiotherapy

 -  Systemic radiotherapy with radioisotopes within the previous 24 weeks

 -  Malignant lymphadenopathy ≥3cm in the short-axis diameter

 -  Presence of visceral metastases

 -  Imminent of established spinal cord compression

 -  Active uncontrolled bacterial, viral or fungal infection

 -  History of another malignancy within the last five years except adequately treated
 basal cell carcinoma of the skin

 -  Organ allografts requiring immunosuppressive therapy.

 -  Any serious uncontrolled concommitant disease

 -  Any psychological, familial, sociological or geographical condition potentially
 hampering compliance with the study protocol and follow-up schedule: those conditions
 should be discussed with the patient before registration in the trial.