Castrate resistant prostate cancer with bone metastases. MedDRA version: 21.1 Level: PT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10005993 Term: Bone metastases System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Xofigo 1000 kBq/mL solution for injection
Product Name: Radium-223 dichloride solution for injection
Product Code: N/A
Pharmaceutical Form: Concentrate for solution for injection/infusion
Sponsors
The Royal Marsden NHS Foundation Trust
The Institute of Cancer Research
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1) Histologically or cytologically confirmed adenocarcinoma of the prostate. 2) Known castration resistant disease defined as: - Castrate serum testosterone level: = 50 ng/dL (2.0nM) and; - Bilateral orchidectomy or on maintenance androgen ablation therapy with LHRH agonist or polyestradiol phosphate throughout the study and; - Serum PSA progression defined by PCWG II criteria (i.e. two consecutive increases in PSA over a previous reference value, each measurement taken at least 1 week apart) 3) Serum PSA value = 2 ng/mL. 4) Available ALP result from a blood sample taken within previous 8 weeks. 5) Multiple skeletal metastases (= 2 hot spots) on bone scintigraphy within previous 12 weeks. 6) Age =18 years. 7) ECOG performance status 0-2. 8) Life expectancy = 6 months. 9) No prior chemotherapy for CRPC (adjuvant chemotherapy for hormone naïve disease is permissible). 10) Adequate laboratory requirements: a. Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L b. Platelet count greater than or equal to 100 x109/L c. Haemoglobin greater than or equal to 10.0 g/dL (100 g/L; 6.2 mmol/L) d. Total bilirubin level less than or equal to 1.5 institutional upper limit of normal (ULN) e. ASAT and ALAT less than or equal to 2.5 x ULN f. Creatinine less than or equal to 1.5 x ULN g. Albumin greater than 30 g/L 11) Willing and able to comply with the protocol, including all assessments, scans, procedures, follow-up visits and examinations. 12) Must be fully informed about the study and has signed the informed consent form. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 19 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 19
Exclusion criteria
Exclusion criteria: 1) Any prior radioisotope therapy. 2) Surgery, radiation, chemotherapy, or other anti-cancer therapy within four weeks prior to randomisation into the study with the exception of LHRH agonists. 3) Intention to commence cytotoxic chemotherapy within six months. 4) Prior other malignancy within three years. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer are allowed. 5) Treatment with any investigational drug within 30 days prior to randomisation into the study. 6) History of visceral metastasis, or visceral metastases, as assessed by chest/abdominal/pelvic CT within previous 8 weeks. 7) Malignant lymphadenopathy exceeding 1.5 cm in short-axis diameter. 8) Known brain or leptomeningeal involvement. 9) Imminent/established spinal cord compression based on clinical findings/MRI (can be re-screened following appropriate treatment). 10) Blood transfusion or erythropoietin stimulating agents within the four weeks prior to randomisation. 11) Faecal incontinence. 12) Unsuitable for MRI (patient refusal or clinical contra-indication). 13) Inadequate organ or bone marrow function. 14) Any other serious illness or medical condition.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal research question is: can response to radium-223, in patients with CRPC and bone metastases, be measured reliably by functional imaging and/or circulating biomarkers? The primary objective is to evaluate patients' response to treatment using a type of imaging technique called whole body diffusion-weighted MRI (DW-MRI). ;Secondary Objective: 1) To evaluate treatment response to radium-223 using 18F fluoride and 18F choline PET/CT scans. 2) To evaluate treatment response using circulating biomarkers in blood (serum) and urine (including alkaline phosphatase (ALP), n-telopeptide, PSA, CTCs, plasma tumour DNA). 3) To evaluate the safety of treatment with radium-223, in terms of what dose is given. EXPLORATORY OBJECTIVES 1) To explore how radium-223 works by evaluating measures of cell proliferation, cell death, DNA damage and DNA repair including Ki67, caspase cleaved cytokeratin, ?H2AX and RAD51 foci formation in bone marrow. 2) To explore the relationship between radium-223 dose and response in terms of functional imaging, tumour molecular characterisation and circulating biomarkers. 3) To explore the predictive value of ALP as a predictive biomarker for response to radium-223 using DW-MRI. 4) To compare the abilty of evaluating treatment response to radium-223 using changes in regional bone plasma clearance (K i) a;Primary end point(s): The proportion of patients showing bone metastases response on diffusion weighted MRI (DW-MRI). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Quantitative and qualitative assessment of treatment response using DW-MRI - Quantitative and qualitative assessment of treatment response using PET imaging - Quantitative response in circulating/urinary biomarkers (ALP, n-telopeptide, PSA, CTCs) - Time to PSA progression - Time to total-ALP progression - Time to first new bone fracture - Incidence and severity of adverse events and laboratory abnormalities - Incidence of treatment discontinuations due to adverse events - Incidence of fractures occurring during and after radium-223 treatment EXPLORATORY - Bone marrow samples: evidence and degree of anti-tumour activity and tumour cell DNA damage using measures of proliferation, apoptosis, DNA damage and DNA repair including Ki67, caspase cleaved cytokeratin, ?H2AX and RAD51 foci formation in bone marrow - Molecular characterisation of CRPC cells, associating subtype with anti-tumour activity - Quantitative and qualitative assessment of treatment response depending on dose cohort (50kBq/kg or 80kBq/kg radium-223) and individual administered dose - Changes in PSA - Changes in total ALP - Quantitative and qualitative assessment of treatment response to radium-223 using DW-MRI according to ALP level. - Difference in treatment response changes as measured by quantitative regional bone plasma clearance (K i) and conventional semi-quantitative SUV parameters. - Association of mean density of lesions on baseline CT scan with response determined by WB DW-MRI | — |
Countries
United Kingdom
Contacts
Public ContactSophie Perry
The Institute of Cancer Research
Outcome results
None listed