UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Efficacy and Safety of Ra-223 as 1st line therapy in combination with alternative anti-androgen therapy for bone metastatic CRPC Patients
Title of the study (Brief title)	1st Ra-223 Therapy Trial
Region	Japan

Condition
Condition	Castration-resistant prostate cancer (CRPC) with bone metastases
Classification by specialty	Urology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To investigate the efficacy and safety of Radium-223 (Ra-223) in combination with alternative anti-androgen therapy as 1st line therapy in Japanese patients with bone metastatic CRPC.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	1) % change in ALP at 12week
Key secondary outcomes	1) % change in ALP at 24week 2) % change in PSA at 12 and 24weeks 3) % changes in Bone markers (BAP, TRACP-5B) at 12 and 24 weeks 4) Bone Scan Index (BSI) 5) QOL( EQ-5D-5L, Japanese Brief Pain Inventory (BPI-J) ) 6) Completion rate of Ra-223 administration 7) Overall Survival (OS) 8) Symptomatic Skeletal Events-Free Survival (SSE-FS) 9) Time to visceral metastases 10) Safety

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Ra-223 (55 kBq/kg i.v.) 6 injections at 4 weeks interval in combination with flutamide.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male
Key inclusion criteria	1) Histologically or cytologically confirmed prostate cancer 2) Patients diagnosed asymptomatic or symptomatic CRPC with bone predominant metastatic and with no visceral metastasis (lymph node (<= 3cm) metastasis is allowed) 3) Confirmed PSA progression with bicalutamide as 1st anti-androgen agent under Combined Androgen Blockade (CAB). Being received or planned to receive flutamide as alternative anti-androgen therapy. 4) Multiple skeletal metastases (>= 2 hot spots) on bone scintigraphy within previous 12 weeks 5) No experience of treatment with neither Abiraterone, Enzalutamide, Docetaxel, nor Cabazitaxel 6) Life expectancy >= 6 months 7) ECOG Performance status : 0 or 1 8) Adequate hematologic, renal, and liver function ･Absolute neutrophil count >= 1.5 x 10^9/L ･Platelet count >= 100 x10^9/L ･Hemoglobin >= 10.0 g/dL ･Total bilirubin, AST, ALT, and creatine <= 1.5 x institutional upper limit of normal (ULN) 9) Fully informed about the study; willing and able to comply with the protocol; must be signed the informed consent form
Key exclusion criteria	1) Treatment history of cytotoxic chemotherapy (including Estramustine 2) Prior hemibody external radiation therapy 3) Systemic radiation therapy with radioisotopes (storontium-89, samarium-153, rhenium-186, or rhenium-188) within previous 24 weeks 4) Prior treatment of Ra-223 5) Blood transfusion or erythropoietin-stimulating agents within the previous 4 weeks 6) Other malignancy treated within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer) 7) History or presence of visceral metastases or brain metastases 8) Malignant lymphadenopathy exceeding 3 cm in short-axis diameter 9) Imminent or established spinal cord compression. Patients with history of spinal cord compression must have completely recovered 10) Presence of liver disorders 11) Any other serious illness or medical condition such as, but not limited to; any uncontrolled infection; cardiac failure NYHA III or IV; Crohn's disease or Ulcerative colitis; Bone marrow dysplasia 12)Unmanageable faecal incontinence 13) Patients who are inappropriate for the participation into this study due to any other reasons judged by each institutional physician
Target sample size	30

Research contact person
Name of lead principal investigator	Shinichi Sakamoto, M.D., PhD
Organization	Graduate School of Medicine and School of Medicine, Chiba University
Division name	Department of Urology
Address	1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba, Japan
TEL	043-226-2134
Email	rbatbat1@gmail.com

Public contact
Name of contact person	Shinichi Sakamoto, M.D., PhD
Organization	Graduate School of Medicine and School of Medicine, Chiba University
Division name	Department of Urology
Address	1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba, Japan
TEL	043-226-2134
Homepage URL
Email	rbatbat1@gmail.com

Sponsor
Institute	Chiba University
Institute
Department

Funding Source
Organization	Bayer Yakuhin, Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2018 Year 01 Month 23 Day

Progress
Recruitment status	Enrolling by invitation
Date of protocol fixation	2017 Year 09 Month 12 Day
Anticipated trial start date	2018 Year 01 Month 29 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2018 Year 01 Month 23 Day
Last modified on	2018 Year 01 Month 23 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035312