Standard Dose Versus High Dose and Versus Extended Standard Dose Radium-223 Dichloride in Castration-resistant Prostate Cancer Metastatic to the Bone

Bayer

Status and phase: Completed; Phase 2

Conditions: Prostatic Neoplasms

Treatments: Drug: Radium-223 dichloride (Xofigo, BAY88-8223)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02023697

16507

2013-003118-42 (EudraCT Number)

Details and patient eligibility

About

This study will assess different doses and regimens of radium-223 dichloride on the incidence of symptomatic skeletal events. Eligible subjects must have castration resistant prostate cancer with 2 or more skeletal metastases documented within 8 weeks of randomization. Subjects will be randomized to one of 3 treatment arms in a 1:1:1 fashion: a standard regimen of radium-223 dichloride of 50 kBq/kg (55 kBq/kg after implementation of NIST update) injections every month for 6 months, a high dose regimen of 80 kBq/kg (88 kBq/kg after implementation of NIST update)injections every month for 6 months or an extended duration regimen of 50 kBq/kg (55 kBq/kg after implementation of NIST update) injections every month for 12 months. Following the treatment phase, subjects will be followed up every 12 weeks for a minimum of 2 years, at which point they will enter a long term follow-up period during which they are seen every 6 months for up to 7 years after the last dose of radium dichloride. Symptomatic skeletal event and safety endpoints will be assessed at each clinic visit. Pain and analgesic use data will be collected every 4 weeks through Week 48. Additionally, radiological assessments including MRI/CT of the abdomen and pelvis and chest CT, as well as technetium-99 bone scans will be performed at Weeks 8, 16, and 24 and continue every 12 weeks thereafter until disease progression is documented in either the bone or in soft tissue. Radiological imaging will be evaluated by blinded central review.

Enrollment: 391 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the prostate

• Castration-resistant disease defined as:

  • Serum testosterone level: ≤ 50 ng/dL (1.7 nmol/L)
  • Bilateral orchiectomy or maintenance on androgen ablation therapy with luteinizing-hormone-releasing hormone (LHRH) agonist or antagonist, or polyestradiol phosphate
  • Serum PSA (Prostate specific antigen) progression defined as 2 subsequent increases in PSA over a previous reference value (a minimum of 2 ng/mL [μg/L]) OR
  • Radiographic evidence of disease progression in bone (according to Prostate Cancer Clinical Trials Working Group 2 [PCWG2] criteria) with or without PSA progression

• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2. In case of ECOG PS 2, the PS has to be due to metastatic prostate cancer to the bone.

• Two or more skeletal metastases (≥ 2 hot spots) on bone scintigraphy within 8 weeks of randomization

Exclusion criteria

• History of visceral metastasis, or visceral metastases
• Lymphadenopathy with lymph nodes exceeding 3 cm in short axis diameter
• Central nervous system (CNS) metastases
• Treatment with cytotoxic chemotherapy for prostate cancer within the previous 4 weeks prior to randomization, or planned treatment with cytotoxic chemotherapy agents for prostate cancer during the treatment period or follow-up
• Chronic conditions associated with non-malignant abnormal bone growth (e.g. confirmed Paget's disease of bone)
• Prior treatment with radium-223 dichloride
• Prior systemic radiotherapy and hemibody external radiotherapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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391 participants in 3 patient groups

Radium-223 dichloride (Standard dose)

Experimental group

Description:

One injection to be administered every 4 weeks up to 6 injections. The dose per injection is 50 kBq/kg body weight (55 kBq/kg after implementation of NIST update).

Treatment:

Drug: Radium-223 dichloride (Xofigo, BAY88-8223)

Radium-223 dichloride (High dose)

Experimental group

Description:

One injection to be administered every 4 weeks up to 6 injections. The dose per injection is 80 kBq/kg body weight (88 kBq/kg after implementation of NIST update).

Treatment:

Drug: Radium-223 dichloride (Xofigo, BAY88-8223)

Radium-223 dichloride (Extended standard dose)

Experimental group

Description:

One injection to be administered every 4 weeks up to 12 injections. The dose per injection is 50 kBq/kg body weight (55 kBq/kg after implementation of NIST update).

Treatment:

Drug: Radium-223 dichloride (Xofigo, BAY88-8223)