The main purpose of this study is to establish a recommended dose of Alpharadin to be used in combination with docetaxel in patients with bone metastases from castration-resistant prostate cancer and to investigate safety and explore efficacy of the recommended dose.
The trial was initially conducted and submitted by Algeta ASA. After acquiring Algeta, Bayer is now the sponsor.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Alpharadin (Radium-223 dichloride) is administered intravenously as a bolus injection.
Docetaxel (75 mg/m\^2) will be administered intravenously every 3 weeks with 5 mg prednisone twice a day continuously and pre-medication with dexamethasone. Step-down to 60 mg/m\^2 is allowed as per the approved docetaxel label.
Unnamed facility
San Francisco, California, United States
Unnamed facility
Evanston, Illinois, United States
Unnamed facility
Baltimore, Maryland, United States
Unnamed facility
Boston, Massachusetts, United States
Number of Subjects With Dose-Limiting Toxicities - Dose Escalation Part
DLT was defined as - Absolute neutrophil count grade greater than or equal to (\>=) 4 (Common Terminology Criteria for Adverse Events \[CTCAE\], Version 4.0: less than \[\<\] 0.5 × 109 per Liter) lasting longer than 7 days without fever despite granulocyte colony-stimulating factor (G-CSF) support). Platelet count Grade \>= 4 (CTCAE, v4.0: \< 25× 109/L) lasting longer than 7 days. Diarrhea Grade \>= 3 (CTAE, v4.0: increase of \>= 7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care in activities of daily living) in spite of optimal use of antidiarrheal medication. Vomiting or constipation Grade \>= 4 (CTCAE, v4.0: life-threatening consequences; urgent intervention indicated). Febrile neutropenia Grade \>= 3 (CTCAE, v4.0).
Time frame: From randomization until 6 weeks post-injection in all dose cohort of dose-escalation part
Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Treatment-Emergent Serious Adverse Events (TESAE) With a CTCAE Grade of 3 or 4
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in patient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
Time frame: From start of study treatment to 6 weeks after study treatment (that is maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) and 8 weeks for serious AEs
Change From Baseline in Serum Biochemistry (Albumin, Protein, Hemoglobin) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
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Unnamed facility
New York, New York, United States
Unnamed facility
Seattle, Washington, United States
Unnamed facility
Villejuif, France
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Change From Baseline in Serum Biochemistry (Alkaline Phosphatase [AP], Alanine Aminotransferase [AAT], Lactate Dehydrogenase [LD]) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Change From Baseline in Serum Biochemistry (Bilirubin, Creatinine) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Change From Baseline in Serum Biochemistry (Calcium, Chloride, Magnesium, Potassium, Phosphate, Sodium, Urea) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Change From Baseline in Serum Biochemistry (Platelets, Leukocytes, Lymphocytes, Neutrophils, Monocytes, Eosinophils, Basophils) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Change From Baseline in Serum Biochemistry (Erythrocytes) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Time frame: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
Changes From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Time frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
Changes From Baseline in Respiratory Rate During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Time frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
Changes From Baseline in Heart Rate During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Time frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
Changes From Baseline in Weight During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.
Time frame: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
Number of Subjects With Physical Examination During the Treatment Period
Any physical examination finding that was classified by the investigator as a clinically significant change (compared with previous examination) was considered an AE, documented on the eCRF, and followed until the outcome was known. The below physical examination findings were recorded and reported. GDASC = General disorders and administration site conditions MND = Metabolism and nutrition disorders SSTD= Skin and subcutaneous tissue disorders MCTD = Musculoskeletal and connective tissue disorders IPPC = Injury, poisoning and procedural complications RTMD = Respiratory, thoracic and mediastinal disorders NBMU = Neoplasms benign, malignant and unspecified (include cysts and polyps) In the below table.
Time frame: From start of study treatment to 6 weeks after study treatment (i.e., maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
Number of Subjects With Signs of Long-Term Radiation Toxicity
Long-term radiation toxicity included incidence of potential late toxicity, such as new primary cancers and bone marrow changes (acute myelogenous leukemia, myelodysplastic syndrome, and aplastic anemia).
Time frame: From start of study treatment upto 12 months