Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Musculoskeletal Diseases

Blood and Lymph Conditions

Prostatic Neoplasms

Neoplasm Metastasis

Bone Neoplasms

Bone Marrow Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neoplastic Processes

Bone Diseases

Hematologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Docetaxel

Dexamethasone

Prednisone

Dexamethasone acetate

Radium Ra 223 dichloride

Tubulin Modulators

Antimitotic Agents

Alpharadin (Radium-223 dichloride) is administered intravenously as a bolus injection. In the randomized phase IIa part of the protocol, the dose established in the dose-escalation part of the protocol (Phase I) will be used, i.e. 5 doses of 50 kBq/kg b.w. every 6 weeks in combination with the approved step-down dose of docetaxel (60 mg/m\^2) administered intravenously every 3 weeks with 5 mg prednisone twice a day continuously and pre-medication with dexamethasone.

Docetaxel (75 mg/m2) 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.

Alpharadin (Radium-223 dichloride) is administered intravenously as a bolus injection.

Radium-223 dichloride (Xofigo, BAY88-8223)

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.

Bayer Study Director

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.

A Study of Alpharadin With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer (CRPC)

A Phase I/IIa Study of Safety and Efficacy of Alpharadin® With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer

Weighted mean area under the curve for the below bone turnover biomarkers were evaluated, ICTP = pyridinoline cross-linked carboxyterminal telopeptide P1NP = N-terminal peptide of procollagen type 1 uCTX-1 = urine C-telopeptide 1

Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least 1 week apart.

CTCs were measured to follow the evolution of the level of CTCs after treatment.

Time to first radiologic or clinical progression is determined by one of the following:

* For soft tissue lesions, the determination is based on Response Evaluation Criteria in Solid Tumors 1.1.
* For bone disease, the determination is based on Prostate Cancer Working Cohort 2 (PCWG2) definitions, which require the appearance of at least 2 new lesions with a confirmatory bone scan at least 6 or more weeks later. For clinical progression, the investigators followed the recommendations of the PCWG25 and used their clinical judgment to determine clinical progression.

PFS defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (radiological or clinical, whichever was earlier) or death (if death occurred before progression was documented). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation.

The overall survival (OS) time in days was calculated as number of days since the day of first dose of study medication until the date of death.

The subject completed the full BPI (short form) paper questionnaire, and clinical staff completed the analgesic log. The test consists of 10 questions addressing severity, location, chronicity, and amount of relief. In question 3, subjects with pain are asked to evaluate the severity of pain at worst in the past 24 hours in a 0 to 10 scale, with 0 indicating no pain, and 10 indicating the worst pain.

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).

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.

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

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.

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).

Bayer

Number of participants at risk are from safety analysis set, please refer to participant flow section.

Subjects received two intravenous injections of Alpharadin (Radium \[Ra\]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on National Institute of Standards and Technology (NIST) 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 milligram per square meter (mg/m\^2) every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation

Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation

Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m\^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.

Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Subjects received two intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m\^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.

Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m\^2 every three weeks.

Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort

Subjects received docetaxel at 75 mg/m\^2 twice daily every three weeks

Docetaxel 75 mg/m^2 - Safety Cohort

Subjects received two intravenous injections of Alpharadin (Radium \[Ra\]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m\^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.

Subjects received docetaxel at 75 mg/m\^2 twice daily every three weeks.

Total

<18 years

Between 18 and 65 years

>65 years

Age, Customized

Gender

The radium 223 dichloride treatment was calculated as 50 kBq per NIST 2010, and would be approximately 55 kBq per NIST 2015 standard. Pharmacokinetic endpoint was deleted as no PK variables were evaluated in the study.

Therapeutic Area Head

Number of Subjects With Dose-Limiting Toxicities - Dose Escalation Part

TEAE CTCAE Grade 3

TEAE CTCAE Grade 4

TESAE

Only participants who received treatment were assessed

Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Treatment-Emergent Serious Adverse Events (TESAE) With a CTCAE Grade of 3 or 4

Albumin Baseline (n= 7,3,7,35,13)

Albumin: Change at Day 106 (n=1,0,0,27,11)

Albumin: Change at Day 190 (n= 0,0,0,24,6)

Protein: Baseline (n= 7,3,7,35,13)

Protein: Change at Day 106 (n=1,0,0,27,11 )

Protein: Change at Day 190 (n= 0,0,0,24,6)

Hemoglobin: Baseline (n= 7,3,7,35,13)

Hemoglobin: Change at Day 106 (n=1,0,0,27,11 )

Hemoglobin: Change at Day 190 (n= 0,0,0,23,6)

Only randomized participants who have this outcome measure tested were assessed

Change From Baseline in Serum Biochemistry (Albumin, Protein, Hemoglobin) During the Treatment Period

AP: Baseline (n= 7,3,7,33,13)

AP: Change at Day 106 (n=1,0,0,27,11)

AP: Change at Day 190 (n= 0,0,0,24,6)

AAT: Baseline (n= 7,3,7,33,13)

AAT: Change at Day 106 (n=1,0,0,27,11 )

AAT: Change at Day 190 (n= 0,0,0,24,6)

LD: Baseline (n= 7,3,7,33,13)

LD: Change at Day 106 (n= 1,0,0,27,11)

LD: Change at Day 190 (n= 0,0,0,24,6)

Change From Baseline in Serum Biochemistry (Alkaline Phosphatase [AP], Alanine Aminotransferase [AAT], Lactate Dehydrogenase [LD]) During the Treatment Period

Bilirubin: Baseline (n= 7,3,7,33,13)

Bilirubin: Change at Day 106 (n= 1,0,0,27,11)

Bilirubin: Change at Day 190 (n= 0,0,0,24,6)

Creatinine: Baseline (n= 7,3,7,33,13)

Creatinine: Change at Day 106 (n= 1,0,0,27,11)

Creatinine: Change at Day 190 (n= 0,0,0,24,6)

Change From Baseline in Serum Biochemistry (Bilirubin, Creatinine) During the Treatment Period

Calcium: Baseline (n= 7,3,7,33,13)

Calcium: Change at Day 106 (n= 1,0,0,27,11)

Calcium: Change at Day 190 (n= 0,0,0,24,6)

Chloride: Baseline (n= 7,3,7,33,13)

Chloride: Change at Day 106 (n= 1,0,0,27,11)

Chloride: Change at Day 190 (n= 0,0,0,24,6)

Magnesium: Baseline (n= 7,3,7,33,13)

Magnesium: Change at Day 106 (n= 1,0,0,27,11)

Magnesium: Change at Day 190 (n= 0,0,0,24,6)

Potassium: Baseline (n= 7,3,7,33,13)

Potassium: Change at Day 106 (n= 1,0,0,27,11)

Potassium: Change at Day 190 (n= 0,0,0,24,6)

Phosphate: Baseline (n= 7,3,7,33,13)

Phosphate: Change at Day 106 (n= 1,0,0,27,11)

Phosphate: Change at Day 190 (n= 0,0,0,24,6)

Sodium: Baseline (n= 7,3,7,33,13)

Sodium: Change at Day 106 (n= 1,0,0,27,11)

Sodium: Change at Day 190 (n= 0,0,0,24,6)

Urea: Baseline (n= 7,3,7,33,13)

Urea: Change at Day 106 (n= 1,0,0,27,11)

Urea: Change at Day 190 (n= 0,0,0,24,6)

Change From Baseline in Serum Biochemistry (Calcium, Chloride, Magnesium, Potassium, Phosphate, Sodium, Urea) During the Treatment Period

Platelets: Baseline (n= 7,3,7,33,13)

Platelets: Change at Day 106 (n= 1,0,0,27,11)

Platelets: Change at Day 190 (n= 0,0,0,23,6)

Leukocytes: Baseline (n= 7,3,7,33,13)

Leukocytes: Change at Day 106 (n= 1,0,0,27,11)

Leukocytes: Change at Day 190 (n= 0,0,0,23,6)

Lymphocytes: Baseline (n= 7,3,7,33,13)

Lymphocytes: Change at Day 106 (n= 1,0,0,27,11)

Lymphocytes: Change at Day 190 (n= 0,0,0,23,6)

Neutrophils: Baseline (n= 7,3,7,33,13)

Neutrophils: Change at Day 106 (n= 1,0,0,27,11)

Neutrophils: Change at Day 190 (n= 0,0,0,23,6)

Monocytes: Baseline (n= 7,3,7,33,13)

Monocytes: Change at Day 106 (n= 1,0,0,27,11)

Monocytes: Change at Day 190 (n= 0,0,0,23,6)

Eosinophils: Baseline (n= 7,3,7,33,13)

Eosinophils: Change at Day 106 (n= 1,0,0,27,11)

Eosinophils: Change at Day 190 (n= 0,0,0,23,6)

Basophils: Baseline (n= 7,3,7,33,13)

Basophils: Change at Day 106 (n= 1,0,0,27,11)

Basophils: Change at Day 190 (n= 0,0,0,23,6)

Change From Baseline in Serum Biochemistry (Platelets, Leukocytes, Lymphocytes, Neutrophils, Monocytes, Eosinophils, Basophils) During the Treatment Period

Erythrocytes: Baseline (n= 7,3,7,33,13)

Erythrocytes: Change at Day 106 (n= 1,0,0,27,11)

Erythrocytes: Change at Day 190 (n= 0,0,0,23,6)

Change From Baseline in Serum Biochemistry (Erythrocytes) During the Treatment Period

SBP: Baseline (n= 7,3,7,33,13)

SBP: Change at Day 22 (n= 6,3,7,33,13)

SBP: Change at Day 43 (n= 6,3,7,32,13)

SBP: Change at Day 64 (n= 6,3,6,30,13)

SBP: Change at Day 85 (n= 0,0,0,28,13)

SBP: Change at Day 106 (n= 0,0,0,28,12)

SBP: Change at Day 127 (n= 0,0,0,27,8)

SBP: Change at Day 148 (n= 0,0,0,25,7)

SBP: Change at Day 169 (n= 0,0,0,25,7)

SBP: Change at Day 190 (n= 0,0,0,24,6)

DBP: Baseline (n= 7,3,7,33,13)

DBP: Change at Day 22 (n= 6,3,7,33,13)

DBP: Change at Day 43 (n= 6,3,7,32,13)

DBP: Change at Day 64 (n= 6,3,6,30,13)

DBP: Change at Day 85 (n= 0,0,0,28,13)

DBP: Change at Day 106 (n= 0,0,0,28,12)

DBP: Change at Day 127 (n= 0,0,0,27,8)

DBP: Change at Day 148 (n= 0,0,0,25,7)

DBP: Change at Day 169 (n= 0,0,0,25,7)

DBP: Change at Day 190 (n= 0,0,0,24,6)

Changes From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period

Spots Global Cancer Trial Database for A Study of Alpharadin With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer (CRPC)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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