A study investigating the safety of radium-223 dichloride with abiraterone acetate and prednisone/prednisolone given to patients with castration-resistant prostate cancer that has spread to bone, and who never had chemotherapy before.

• Register: EUCTR
• Last refreshed on: 6 May 2024
• Main ID: EUCTR2013-003438-33-BE
• Date of registration: 13/03/2014
• Prospective Registration: Yes
• Primary sponsor: Bayer AG
• Public title: A study investigating the safety of radium-223 dichloride with abiraterone acetate and prednisone/prednisolone given to patients with castration-resistant prostate cancer that has spread to bone, and who never had chemotherapy before.
• Scientific title: A phase III randomized, double-blind, placebo-controlled trial of radium-223 dichloride in combination with abiraterone acetate and prednisone/prednisolone in the treatment of asymptomatic or mildly symptomatic chemotherapy-naïve subjects with bone predominant metastatic castration-resistant prostate cancer (CRPC)
• Date of first enrolment: 13/04/2014
• Target sample size: 800
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003438-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Canada, China, Finland, France, Germany, Israel, Italy, Japan, Netherlands, Norway, Poland, Russian Federation, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

Key inclusion & exclusion criteria

Inclusion criteria:
- Histologically confirmed adenocarcinoma of the prostate
- Male subjects of age = 18 years. The lower limit may be higher if legally required in the participating country
- Prostate cancer progression documented by prostate specific antigen according to the Prostate Cancer Working Group 2 (PCWG2) criteria or radiological progression according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
- Two or more bone metastases on bone scan within 4 weeks prior to randomization with no lung, liver, other visceral and/or brain metastasis.
- Asymptomatic or mildly symptomatic prostate cancer.
- Subjects who received combined androgen blockade with an anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to enrollment.
- Maintenance of medical castration3 or surgical castration with testosterone less than 50 ng/dL (1.7 nmol/L). If the subject is being treated with luteinizing hormonereleasing hormone (LHRH) agonists or antagonists (subject who has not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
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 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion criteria:
- Prior cytotoxic chemotherapy for the treatment of CRPC, including taxanes, mitoxantrone and estramustine
- Administration of immunotherapies (e.g., sipuleucel-T) within 4 weeks before randomization
- Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone/prednisolone twice daily.
- Pathological finding consistent with small cell carcinoma of the prostate
- History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations
- History of or known brain metastasis.
- Malignant lymphadenopathy exceeding 3 cm in shortaxis diameter.
- Blood transfusion or erythropoietin stimulating agents prior 4 weeks of screening and during the whole screening period before randomization
- Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI).
Subjects with history of spinal cord compression should have completely recovered
- Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or
anytime during the 4- week period prior to randomization.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Asymptomatic or mildly symptomatic chemotherapy-naïve bone predominant metastatic castration-resistant prostate cancer
MedDRA version: 20.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Xofigo
Product Name: Radium RA 223 dichloride
Product Code: BAY88-8223
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Radium-223 dichloride
CAS Number: 444811-40-9
Current Sponsor code: BAY 88-8223
Other descriptive name: RADIUM-223 DICHLORIDE
Concentration unit: kBq/ml kilobecquerel(s)/millilitre
Concentration type: equal
Concentration number: 1100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Trade Name: ZYTIGA
Product Name: Abiraterone acetate
Product Code: JNJ-212082
Pharmaceutical Form: Tablet
INN or Proposed INN: ABIRATERONE ACETATE
CAS Number: 154229-19-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: Deltacortene

Product Name: Prednisone
Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisone
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Secondary Objective: The secondary objectives are to compare overal survival, time to opiate use for cancer pain, time to pain progression, time to cytotoxic chemotherapy, radiological progression free survival, acute and long term safety.

Main Objective: The primary objective is to compare the clinical benefit of radium-223 dichloride versus placebo in combination with abiraterone and prednisone/prednisolone in asymptomatic or mildly symptomatic chemotherapynaïve bone predominant metastatic castration-resistant prostate cancer patients.

Timepoint(s) of evaluation of this end point: At 3 years

Primary end point(s): Symptomatic skeletal event free survival(SSE-FS)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. At 3 years for interim
At 6 years for final
2. At 3 years
3. At 3 years
4. At 3 years
5. At 3 years
6. Up to 3 years

Secondary end point(s): 1. Overall Survival
2. Time to opiate use for cancer pain
3. Time to pain progression
4. Time to cytotoxic chemotherapy
5. Radiological progression free survival (rPFS)
6. Number of participants with adverse events as a measure of safety and tolerability

Secondary ID(s)

2013-003438-33-IT

BAY88-8223/15396

Source(s) of Monetary Support

Bayer AG

Ethics review

Status: Approved
Approval date: 09/04/2014
Contact:

Results

• Results available: Yes
• Date Posted: 28/02/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-003438-33/results