Phase II open-label study to evaluate the efficacy and safety of Radium-223 dichloride in combination with external beam radiotherapy (EBRT) vs. external beam radiotherapy alone in the treatment of advanced castration resistant prostate carcinoma with limited bone metastases. To evaluate if time 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) of Radium-223 dichloride combined with EBRT is superior compared to EBRT alone.
This is an international, multi-center, open-label, prospective, phase II study designed to assess the efficacy of radiation therapy in combination with Radium-223 dichloride in patients diagnosed with CRPC and oligo metastases bone disease. All patients enrolled in this study will have signed an informed consent form (ICF) and will adhere to all inclusion and exclusion criteria. During the treatment period, patients will be followed on an ongoing basis for safety and quality of life (QoL). Safety assessments will include the collection of all AEs of any grade, serious adverse events (SAEs), adverse event (AEs) corresponding to symptoms arising from bone metastases, laboratory values, (WHO/ECOG) performance status (PS). Documentation of the date of disease progression will be performed at intervals and imaging methods (bone scans and CR/MRI) described in the study protocol. Quality of life will be measured by patient assessment using a validated questionnaire, the Brief Pain Inventory Short Form (BPI-SF), the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C15-PAL and the EORTC QLQ- Bone Metastases (BM) 22. Follow-up assessments for safety AEs and SAEs, and the occurrence of secondary malignancies will be conducted every 3-12 months until the patient dies or until the study is terminated by the sponsor. If the patient can no longer travel to the clinical site, he will be followed up for survival only, i.e., the long term follow-up phase of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
274
Arm A: EBRT and timely sequential start with Radium-223 dichloride 55 kBq/kgbw (6 i.v. injections every 4 weeks) and best supportive care until progression or intolerable toxicity.
Arm B: External beam radiotherapy (EBRT)-\>-\>conventional or high dose radiotherapy
Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
Dresden, Germany
RECRUITINGUniversitätsklinikum Freiburg, Klinik für Strahlenheilkunde
Freiburg im Breisgau, Germany
RECRUITINGUniversitätsmedizin Mainz, Klinik und Poliklinik für Nuklearmedizin
Mainz, Germany
RECRUITINGKlinikum der Universität München
München, Germany
RECRUITINGUniversitätsklinikum Tübingen
Tübingen, Germany
RECRUITINGUniversitätsklinikum Würzburg
Würzburg, Germany
RECRUITINGTime to radiological progression free survival (PFS) rate
measured every 3 month by Bone Scan and MRI or CT until Follow up 7 (month 24) and after that in long term follow up every 6 month
Time frame: randomization to radiological progression
Time to local progression in any of the EBRT treated bone metastases of conventional radiotherapy (CRT) vs. High-dose image-based conformal radiotherapy (HIRT) treatment techniques
measured every 3 month by Bone Scan, Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) until month 24 after that in long term follow up every 6 month with open end
Time frame: Time to local progression in any of the EBRT treated bone metastases
Overall survival
Follow up every 3 month until month 24 and after that in long term follow up every 6 month
Time frame: randomization to death
Time to distant bone metastasis progression outside the RT target volumes
Follow up every 3 month until month 24 and than in long term follow up every 6 month measured by increasing of PSA, CT/MRI
Time frame: Screening to FU 7 (after 24 months) and than in long term follow up every 6 month
Time to Skeletal Related Event (SRE)
measured every 3 month by Bone Scan, Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) until month 24 and than in long term follow up every 6 month with open end
Time frame: Screening to FU 7 (after 24 months) and than in long term follow up every 6 month
Pain control
measured every 3 month by the Brief Pain Inventory Short Form (BPI-SF), the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C15-PAL and the EORTC QLQ- Bone Metastases (BM) 22 until month 24 and than in long term follow up every 6 month
Time frame: Screening to FU 7 (after 24 months) and than in long term follow up every 6 month
Disease Control Rate (DCR); Response rates according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Follow up every 3 month until month 24 measured by RECIST criteria and than in long term follow up every 6 month
Time frame: Screening to FU 7 (after 24 months) and than in long term follow up every 6 month
PSA response, time to PSA response and time to PSA normalization
Follow up every 3 month until month 24 and after that long term follow up every 6 month measured by PSA level
Time frame: Screening to FU 7 (after 24 months) and than in long term follow up every 6 month
Bone alkaline phosphatase (ALP) response, time to bone ALP response
Follow up every 3 month until month 24 and than long term follow up every 6 month measured by blood level
Time frame: Screening to FU 7 (after 24 months) and than in long term follow up every 6 month
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