Patients with mCRPC with asymptomatic progression while on abiraterone acetate or enzalutamide MedDRA version: 19.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: XOFIGO
Pharmaceutical Form: Solution for injection
INN or Proposed INN: nd
CAS Number: nd
Current Sponsor code: radium223
Other descriptive name: RADIUM RA 223 DICHLORIDE
Concentration uni
Sponsors
Medica Scientia Innovation Research (MedSIR ARO)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: • Subject is an adult = 18 years at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines. • Subject has histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features. • Subject has bone metastases due to the prostate cancer and absence of visceral metastases. • Subject has a serum testosterone of = 1.7 nmol/L (or = 50 ng/dL) at screening. • Subject must have received a minimum of 24 weeks of treatment with abiraterone acetate or enzalutamide within its approved label indication and has discontinued use at least four weeks prior to start of study drug at day 1. • Prior use of docetaxel is allowed in castration-naïve patients (maximum of six cycles). • Subject receives and will continue to receive ongoing androgen deprivation with luteinizing releasing hormone (LHRH) analogue therapy throughout the course of the study or has had a bilateral orchiectomy. • Subject is asymptomatic from prostate cancer, defined as patients with the score on brief pain inventory (short form) (BPI-SF) Question #3 must be zero or one and no use of opiate analgesics for prostate cancer-related pain currently or anytime within two weeks prior to screening. • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 at screening. • Subject receiving bisphosphonate or other approved bone-targeting therapy must have been on stable doses for at least four weeks prior to start of study drug at day 1. • Subject has a life expectancy of more than or equal to 12 months. • Subject agrees not to participate in another interventional study while on study drug. • Subject and his female partner who is of childbearing potential must use two acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for six months after final study drug administration. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 52 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
Exclusion criteria: Any patient meeting ANY of the following criteria will be excluded from the study: • Subject has received any anti-neoplastic therapy (including ketokonazol and chemotherapy) following abiraterone acetate or enzalutamide discontinuation and prior to start of study drug at day 1. • Subject has known or suspected brain metastases or active leptomeningeal disease. • Subject has concurrent disease or any clinically significant abnormality following the investigator’s review of the physical examination and safety laboratory tests at screening, which in the judgment of the investigator would interfere with the subject's participation in this study or evaluation of study results. • Subject has a history of another invasive cancer within three years prior to screening, with the exceptions of non-melanoma skin cancers or a non-infiltrating muscle bladder cancer that have a remote probability of recurrence in the opinion of the investigator in consultation with the medical monitor. • Subject had major surgery within one month prior to screening. • Subject has received investigational therapy within 28 days or 5 half lives, whichever is longer, prior to start of study drug at day 1. • Subject has absolute neutrophil count 1.5 times the upper limit of normal (ULN) at screening, except for subjects with documented Gilbert’s syndrome. • Subject has creatinine > 2.5 mg/dL at screening. • Subject has albumin = 30 g/L (or = 3.0 g/dL) at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of radium-223 in asymptomatic patients with mCRPC who have progressed while on abiraterone acetate or enzalutamide treatment.;Secondary Objective: • Safety profile. • To determine the association between AR-V7 status (positive vs. negative) and progression-free survival (PFS). • To establish the relationship between circulating tumor cells (CTCs) number and ctDNA levels with radium-223 efficacy.;Primary end point(s): The primary endpoint of this study is to assess the efficacy of radium-223 in terms of radiological rPFS.;Timepoint(s) of evaluation of this end point: PFS is a composite endpoint defined as the time from the start of the radium-223 treatment to disease progression in bone or soft-tissue, symptoms, or death, according to the PCWG2 criteria. Objective radiographic disease progression is defined as the presence of at least one of the following conditions: • Bone lesion progression (appearance of = two new bone lesions compared to baseline). • Soft-tissue lesion progression according to the RECIST criteria version 1.1. • Presence of skeletal events. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety AEs will be evaluated using the NCI-CTCAE version 4.0. Grade 3 or 4 AEs and serious adverse events (SAEs) will be assessed to determine the safety and tolerability of the various combinations of drugs. Efficacy • Radiographic progression-free survival (rPFS) depending on AR-V7 status. • Overall survival (OS). • Time to first symptomatic skeletal-related event (SRE). • Time to PSA response according to the ALSYMPCA study criteria. • Determination percentage of PSA response. • Alkaline phosphatase level response (AF), normalization of alkaline phosphatase level, according to the ALSYMPCA study criteria. Molecular aspects • Assessment of AR-V7 mutation evolution during the study treatment. • Determination changes in CTCs number and ctDNA levels during the study treatment.;Timepoint(s) of evaluation of this end point: Safety will be evaluated continuosly during all study. Efficacy will be evaluated globally after the conclusion of data entry in the CRF and locally by each investigator taking into account the clinic benefit for each patient, case by case | — |
Countries
Spain
Contacts
Public ContactSilvia Monzonís
Medica Scientia Innovation Research (MedSIR ARO)
Outcome results
None listed