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
- Conditions
- C61C79.5Malignant neoplasm of prostateSecondary malignant neoplasm of bone and bone marrow
- Registration Number
- DRKS00007787
- Lead Sponsor
- niversitätsklinikum Freiburg
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting stopped after recruiting started
- Sex
- Male
- Target Recruitment
- 5
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. Age = 18 and = 85 years
2. Patients with progressive castration resistant prostate cancer (CRPC) with 1-5 bone metastases for whom Radium-223 dichloride constitutes first-line cytostatic treatment
3. Primary tumor (and its local recurrence, if applicable) controlled by effective local treatment
4. If diagnosed, pelvic lymph node metastases controlled by effective local treatment
5. 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
6. 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
7. Life expectancy of at least 6 months.
8. Zubrod (WHO/ECOG) Performance Status (PS) 0 or 1
9. 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 < 1.5 times the institutional upper limit of normal (ULN)
- ALT and AST < 2.5 x institutional upper limit of normal (ULN)
- Serum creatinine < 2 x upper limit of normal.
10. Patient has or has had symptoms (e. g. pain or micro-fractions) from bone metastases
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 his 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. Radiotherapy for prostate cancer manifestations other than study treatment if not given with curative intent to prostate fossa and/or pelvic lymph nodes
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
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method 1. Overall survival<br>2. Time to local progression in any of the EBRT treated bone metastases of CRT vs. HIRT treatment techniques<br>3. Time to distant bone metastasis progression outside the RT target volumes<br>4. Time to SRE (using the same criteria as in ALSYMPCA)<br>5. Pain control (weekly visual analog score and Brief pain inventory short form”)<br>6. Disease Control Rate (DCR); Response rates (CR, PR, SD according to RECIST criteria)<br>7. PSA response, time to PSA response and time to PSA normalization<br>8. Bone ALP response, time to bone ALP response<br>