E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Castrate Resistant Prostate Cancer/Hormone-Refractory Prostate Cancer patients with bone metastasis |
|
E.1.1.1 | Medical condition in easily understood language |
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 | 16.0 |
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 assess acute and long term safety and overall survival in patients with castration-resistant (hormone-refractory) prostate cancer.
|
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Eligible patients will conform to all of the inclusion criteria listed below:
• Has provided written informed consent. Subjects must be able to understand and be willing to sign the written informed consent form (ICF). A signed ICF must be appropriately obtained prior to the conduct of the any trial-specific procedure.
• Age ≥ 18 years
• Histologically or cytologically confirmed prostate cancer
• Patients diagnosed with progressive bone predominant metastatic CRPC/HRPC with at least two skeletal metastases on imaging with no lung, liver, and/or brain metastasis (lymph node only metastasis is allowed). A standard of practice bone scan for the documentation of at least 2 skeletal metastases can be used as long as it is within 3 months of planned start of treatment. If no bone scan within a 3 month window is available, then a technetium-99m bone scan will be obtained at screening (within 28 days of planned start of study drug).
• Progressive disease is defined either by:
o The appearance of new bone lesions. If progression is based on new lesion(s) on bone imaging only without an increase in prostate specific antigen (PSA), PSA values from 3 assessments within the last 6 months must be provided; OR
o In the absence of new bone lesions by 2 subsequent increases in serum PSA over previous reference value, which should not be more than 6 months before screening, each measured at least 1 week apart with the last PSA ≥ 5 ng/mL. (The reference value time point 1, is defined as the last PSA measured before increases are documented, with subsequent values obtained a minimum of 1 week apart. If the PSA at time point 3 is greater than the PSA at time point 2, then eligibility has been met. If the PSA at time point 3 is not greater than the PSA at time point 2 but the PSA value at time point 4 and/or time point 5 is, the patient is eligible assuming that other criteria are met)
• No intention to use cytotoxic chemotherapy within the next 6 months
• Life expectancy ≥ 6 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
• Adequate hematological, liver, and renal function
o Absolute neutrophil count (ANC) ≥ 1.5 x109/L
o Platelet count ≥ 100 x109/L
o Hemoglobin ≥ 10.0 g/dL (100 g/L; 6.2 mmol/L)
o Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN)
o Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
o Creatinine ≤ 1.5 x ULN
o Albumin > 25 g/L
• Willing and able to comply with the protocol, including follow-up visits and examinations
|
|
E.4 | Principal exclusion criteria |
Eligible patients must not meet any of the exclusion criteria listed below:
• Treatment with an investigational drug within previous 4 weeks, or planned during the treatment period or follow-up
• Eligible for first course of docetaxel, i.e., patients who are fit enough, willing, and who are located where treatment with docetaxel is available
• Treatment with cytotoxic chemotherapy within previous 4 weeks, prior to screening, or failure to recover from AEs due to cytotoxic chemotherapy administered more than 4 weeks previous prior to screening (however, ongoing neuropathy is permitted)
• Treatment with any prior anticancer theraphy (including, therapeutic vaccines), other than the permitted Standard of Care therapies (please refer to section 6.9), are allowed provided that they are completed 28 days before treatment or 5.5 half-lives of the drugs involved have elapsed before treatment start.
• Prior hemibody external radiotherapy is excluded. Patients who received other types of prior external radiotherapy are allowed provided that the bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count and platelets.
• Received systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or radium-223 dichloride) for the treatment of bony metastases
• Other malignancy treated within the last 3 years (except non melanoma skin cancer or low-grade superficial bladder cancer)
• Visceral metastases as assessed by abdominal or pelvic computed tomography (CT) (or other imaging modality based on institutional standard of care)
• Presence of brain metastases
• Lymphadenopathy exceeding 6 cm in short-axis diameter
• Any size pelvic lymphadenopathy if it is thought to be a contributor to concurrent hydronephrosis.
• Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Patients with history of spinal cord compression should have completely recovered.
• Any other serious illness or medical condition, such as but not limited to:
o Any infection ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade 2
o Cardiac Failure New York Heart Association (NYHA) Class III or IV
o Crohn’s disease or ulcerative colitis
o Bone marrow dysplasia
• Fecal incontinence
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Acute (during the treatment period and up to 30 days post-treatment) and long-term (30 days post-treatment and onward) safety
• Overall survival defined as the time (days) from the start of therapy to death, due to any cause. Patients alive at the time of analysis will be censored at the last date known to be alive. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
During the treatment period and up to 30 days post-treatment, and longterm 30 days post-treatment and onward. |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
To assess the overall survival of this patient population.
Quality of Life will be evaluated by BPI-SF (this is not primary outcome/variable) |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | 1 |
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 | 170 |
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 |
Austria |
Belgium |
Canada |
Czech Republic |
Denmark |
Finland |
Germany |
Ireland |
Israel |
Italy |
Mexico |
Netherlands |
Norway |
Poland |
Russian Federation |
Spain |
Sweden |
Switzerland |
United Kingdom |
|
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
|
For each participating European Union (EU) country, the end of the study according to the EU Clinical Trial Directive will be reached when the last visit of the last patient for all centers in the respective country has occurred.
Sites/Countries will be closed to enrolment as marketing approval of radium-223 dichloride is obtained for that country. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |