Bone metastases in advanced castration resistant prostate carcinoma. MedDRA version: 19.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.1 Level: LLT Classification code 10005993 Term: Bone metastases System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.1 Level: PT Classification code 100
Conditions
Interventions
Trade Name: Xofigo® (Radium 223 dichloride)
Pharmaceutical Form: Injection
Sponsors
Universitätsklinikum Freiburg
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Eligible patients will conform to all of the inclusion criteria listed below: 1. 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. Enrollment (entry) in the study is defined as the signing of the informed consent. 2. Age = 18 and = 85 years 3. Patients with progressive castration resistant prostate cancer (CRPC) with 1-5 bone metastases for whom Radium-223 dichloride constitutes first-line cytostatic treatment 4. Primary tumor (and its local recurrence, if applicable) controlled by effective local treatment 5. If diagnosed, pelvic lymph node metastases controlled by effective local treatment 6. At least 1 not previously locally treated skeletal metastasis on bone scan without non-bone distant metastases (e.g. lung, liver, and/or brain metastases) and without pathologically enlarged lymph nodes above the pelvis 7. Progressive disease is defined either by: - The appearance of new bone lesions. If progression is based on new lesion(s) on bone scan only without an increase in prostate specific antigen (PSA), PSA values from 3 assessments within the last 6 months must be provided; OR - In the absence of new bone lesions by 2 consecutive 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 8. Life expectancy of at least 6 months 9. Zubrod (WHO/ECOG) Performance Status (PS) 0 or 1 10. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of therapy: - Hemoglobin > 10.0 g/dl - Absolute neutrophil count (ANC) >1,500/µl - Platelet count >100,000/µl - Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 137
Exclusion criteria
Exclusion criteria: Excluded medical conditions: 1. More than 5 not previously locally treated bone metastases as diagnosed by bone scintigraphy; 2. Visceral or lymph node metastases above the pelvis as assessed by computed tomography (CT) (or other imaging modality) 3. History of HIV infection or chronic hepatitis B or C 4. Active clinically serious infections (> grade 2 NCI-CTC version 4.03) 5. History of organ allograft 6. Patients undergoing renal dialysis 7. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study if not in complete remission for at least 5 years since date of diagnosis, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry. 8. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results 9. Imminent or history of spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI) 10. Any other serious illness or medical condition, such as but not limited to: - Cardiac failure New York Heart Association (NYHA) III or IV - Crohn’s disease or ulcerative colitis - Bone marrow dysplasia 11. Fecal incontinence 12. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study 13. Known allergy to Radium-223 dichloride (i.e. to active substance or one of the constituents) Excluded therapies and medications, previous and concomitant: 1. Anticancer chemo- or targeted therapy for CRPC (e.g. docetaxel or cabazitaxel) 2. Local relapse in previously irradiated osseous metastases 3. Major surgery within 4 weeks of study entry. 4. Systemic therapy with radionuclides (e.g., strontium-89, samarium-153, rhenium-186, or rhenium-188, or radium-223 dichloride) for the treatment of bone metastases 5. Autologous bone marrow transplant or stem cell rescue within 4 months of study entry 6. Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study entry or during the study] 7. Investigational drug therapy outside of this trial during or within 4 weeks of study entry
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Radiological progression-free survival (rPFS) defined as time from randomization to radiological progression or death;Primary end point(s): Time to radiological progression-free survival defined as time from randomization to radiological progression according to the “Recommendations of the Prostate Cancer Clinical Trials Working Group” published by Scher et al. (JCO 2008) (based on new lesions in bone scan and CT /MRI or death) ;Timepoint(s) of evaluation of this end point: Intent-to-treat analysis at the end of study.;Secondary Objective: 1. Overall survival 2. Time to local progression in any of the EBRT treated bone metastases of CRT vs. HIRT treatment techniques 3. Time to distant bone metastasis progression outside the RT target volumes 4. Time to SRE (using the same criteria as in ALSYMPCA) 5. Pain control (weekly visual analog score and “Brief pain inventory short form” (BPI-SF)) 6. Disease Control Rate (DCR); Response rates (CR, PR, SD according to RECIST criteria) 7. PSA response, time to PSA response and time to PSA normalization 8. Bone ALP response, time to bone ALP response Explorative objectives: - One year bone metastasis progression free survival - Health-related Quality of Life (EORTC QLQ-C15-PAL and EORTC QLQ-BM22) - Biomarker program using blood samples to be defined in more detail in a separate protocol. - Safety and tolerability - Time to opiate use for cancer pain - Time to pain progression - Local symptomatic treatment failure (LSTF) - Local treatment failure (LTF) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival 2. Time to local progression in any of the EBRT treated bone metastases of CRT vs. HIRT treatment techniques 3. Time to distant bone metastasis progression outside the RT target volumes 4. Time to SRE (using the same criteria as in ALSYMPCA) 5. Pain control (weekly visual analog score and “Brief pain inventory short form”) 6. Disease Control Rate (DCR); Response rates (CR, PR, SD according to RECIST criteria) 7. PSA response, time to PSA response and time to PSA normalization 8. Bone ALP response, time to bone ALP response Explorative: - One year bone progression free survival - Health-related Quality of Life (PAL15 + BM22) - Biomarker program using blood samples to be defined by a separate protocol in more detail. - Safety and tolerability - Time to opiate use for cancer pain defined as the interval from the date of randomization to the date of opiate use. - Time to pain progression defined as the interval from randomization to the first date a subject experiences a BPI-SF increase by =30% and at least 2 points from baseline in the worst pain index score (WPS) observed at 2 consecutive evaluations =4 weeks apart without decrease in analgesic usage score. - Local symptomatic treatment failure (LSTF) defined as the time from randomization to the occurrence of one of the following: Development, increase or recurrence of tumor related symptoms at irradiated bone metastases with - Increase of local symptoms by one grade according to NCI-AE v4.03 or - Recurrence of local symptoms to the same grade according to NCI-AE v4.03 as assessed at randomization or - Development of new local symptoms of any grade according to NCI-AE v4.03 - Local treatment failure (LTF) defined as the time from randomization to the occurrence of one of the following: - Local SSE-FS at irradiated bone metastases - Evidence of radiological progression measured according to methodology from RECIST v1.1 (the longest diameter includ | — |
Countries
Germany
Contacts
Public ContactStudienbüro
Universitätsklinik Freiburg
Outcome results
None listed