a-RT; Phase II open-label study to evaluate the efficacy and safety ofRadium-223 dichloride in combination with external beam radiotherapy (EBRT) vs.EBRT alone in the treatment of advanced castration resistant prostatecarcinoma with limited bone metastases
- Conditions
- Bone metastases in advanced castration resistant prostate carcinoma.MedDRA version: 19.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.1Level: LLTClassification code 10005993Term: Bone metastasesSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.1Level: PTClassification code 10062904Term: Hormone-refractory prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-004879-13-DE
- Lead Sponsor
- niversitätsklinikum Freiburg
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 274
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 < 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.
11. Patient has or has had symptoms (e. g. pain or micro-fractions) from bone metastases
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 137
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 137
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method