E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Castration resistant prostate cancer with bone metastasis |
|
E.1.1.1 | Medical condition in easily understood language |
Patients with prostate cancer which has spread to the bone |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036916 |
E.1.2 | Term | Prostate cancer stage D |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate efficacy as measured by symptomatic skeletal event-free survival (SSE-FS) of radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 28 days for up to 6 doses compared to radium-223 dichloride 80 kBq/kg (88 kBq/kg after implementation of NIST update) every 28 days for up to 6 doses in subjects with CRPC metastatic to the bone not previously receiving radium-223 dichloride
• To evaluate efficacy as measured by SSE-FS of radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 28 days for up to 6 additional doses compared to no further radium-223 dichloride treatment in subjects with CRPC metastatic to the bone who previously received radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 28 days for up to 6 doses, and
survived SSE-free and are eligible for further radium-223 dichloride treatment. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate safety and tolerability
• To evaluate overall survival (OS)
• To evaluate pain improvement rate
• To evaluate time to pain progression
• To evaluate time to first SSE
• To evaluate time to radiological progression
• To evaluate radiological progression-free survival (rPFS)
• To evaluate change in analgesic use as measured by the Analgesic Quantification Algorithm (AQA). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically or cytologically confirmed adenocarcinoma of the prostate
- Castration-resistant disease defined as:
a Serum testosterone level: ≤ 50 ng/dL (1.7 nmol/L)
b Bilateral orchiectomy or maintenance on androgen ablation therapy with luteinizing-hormone-releasing hormone (LHRH) agonist or antagonist, or polyestradiol phosphate
c Serum PSA progression defined as 2 subsequent increases in PSA over a previous reference value, with a PSA value of ≥ 2 ng/mL at the time of the second increase
OR
Radiographic evidence of disease progression in bone (according to Prostate Cancer Clinical Trials Working Group 2 [PCWG2] criteria) with or without PSA progression
- Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2. In case of ECOG PS 2, the PS has to be due to metastatic prostate cancer to the bone.
- Two or more skeletal metastases (≥ 2 hot spots) on bone scintigraphy within 8 weeks of randomization |
|
E.4 | Principal exclusion criteria |
- History of visceral metastasis, or visceral metastases
- Lymphadenopathy with lymph nodes exceeding 3 cm in short axis diameter
- Central nervous system (CNS) metastases
- Treatment with cytotoxic chemotherapy for prostate cancer within the previous 4 weeks prior to
randomization, or planned treatment with cytotoxic chemotherapy agents for prostate cancer during the
treatment period or follow-up
- Chronic conditions associated with non-malignant abnormal bone growth (e.g. confirmed Paget's disease of bone)
- Prior treatment with radium-223 dichloride
- Prior systemic radiotherapy and hemibody external radiotherapy |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1) Symptomatic skeletal event-free survival (SSE-FS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization up to a maximum of 8 years, assessed every month during treatment and every 12 weeks during active follow-up |
|
E.5.2 | Secondary end point(s) |
1) Overall Survival (OS)
2) Time to first symptomatic skeletal event (SSE)
3) Radiological progression-free survival (rPFS)
4) Time to radiological progression
5) Pain improvement rate
6) Time to pain progression
7) Change in 24 hour analgesic use
8) Number of participants with treatment-emergent adverse events
or serious adverse events as a measure of safety and tolerability |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) From randomization up to a maximum of 8 years, assessed every month during treatment and every 12 weeks during active follow-up and every 6 months in long term follow-up
2) From randomization up to a maximum of 8 years, assessed every month during treatment and every 12 weeks during active follow-up
3) From randomization up to a maximum of 3 years, assessed every 12 weeks
4) From randomization up to a maximum of 3 years, assessed every 12 weeks
5) Up to 48 weeks
6) Up to 48 weeks
7) Up to 48 weeks
8) From randomization up to 8 years |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
Chile |
Czech Republic |
Finland |
France |
Germany |
Israel |
Italy |
Korea, Republic of |
Poland |
Spain |
Sweden |
Taiwan |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study according to the EU Clinical Trial Directive will be reached when the last visit of the last subject for all centers in the respective country has occurred. However, as the primary endpoint of this study is event-based, the end of the study as a whole will only be reached when this endpoint has been achieved in subjects in all participating centers (EU and non-EU). |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |