Phase 2 N=391 Randomized Treatment

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

Prostatic Neoplasms

Bottom Line

View on ClinicalTrials.gov: NCT02023697 ↗

Enrolled (actual)

391

Serious AEs

26.5%

Results posted

Jul 2018

Primary outcome: Primary: Number of Participants With an Event Defining SSE Free Survival - High Dose vs. Standard Dose — 85; 118 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Radium-223 dichloride (Xofigo, BAY88-8223) (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: Male
Sponsor: Bayer
Primary completion: Mar 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With an Event Defining SSE Free Survival - High Dose vs. Standard Dose	85; 118	—
PRIMARY Symptomatic Skeletal Event-Free Survival - High Dose vs. Standard Dose	12.9; 12.3	0.7047
PRIMARY Number of Participants With an Event Defining SSE Free Survival - Extended Dose vs. Standard Dose	41; 40	—
PRIMARY Symptomatic Skeletal Event-Free Survival - Extended Dose vs. Standard Dose	13.2; 10.8	0.3134
PRIMARY Number of Participants With an Event Defining SSE Free Survival - Three Dose Groups As Randomized	80; 85; 92	—
PRIMARY Symptomatic Skeletal Event Free Survival - Three Dose Groups As Randomized	13.1; 12.9; 9.6	—
SECONDARY Number of Participants With an Overall Survival Event - High Dose vs. Standard Dose	89; 106	—
SECONDARY Overall Survival - High Dose vs. Standard Dose	16.0; 14.9	0.6205
SECONDARY Number of Participants With an Overall Survival Event - Extended Dose vs. Standard Dose	43; 38	—
SECONDARY Overall Survival - Extended Dose vs. Standard Dose	16.5; 15.2	0.9958
SECONDARY Number of Participants With an Overall Survival - Three Dose Groups As Randomized	83; 89; 93	—
SECONDARY Overall Survival Event - Three Dose Groups as Randomized	15.8; 16.0; 14.4	—
SECONDARY Number of Participants With First Symptomatic Skeletal Event - High Dose vs. Standard Dose	42; 62	—
SECONDARY Time to First Symptomatic Skeletal Event - High Dose vs. Standard Dose	24.1; 26.3	0.7461
SECONDARY Number of Participants With First Symptomatic Skeletal Event - Extended Dose vs. Standard Dose	19; 25	—
SECONDARY Time to First Symptomatic Skeletal Event - Extended Dose vs. Standard Dose	NA; 19.5	0.1550
SECONDARY Number of Participants With First Symptomatic Skeletal Event - Three Dose Groups as Randomized	37; 42; 48	—
SECONDARY Time to First Symptomatic Skeletal Event - Three Dose Groups as Randomized	NA; 24.1; 18.8	—
SECONDARY Number of Participants With a Radiological Progression Event-Free - High Dose vs. Standard Dose	77; 141	—
SECONDARY Radiological Progression Free Survival - High Dose vs. Standard Dose	7.5; 6.0	0.8284
SECONDARY Number of Participants With a Radiological Progression Event-Free - Extended Dose vs. Standard Dose	49; 47	—
SECONDARY Radiological Progression Free Survival - Extended Dose vs. Standard Dose	8.9; 9.0	0.7896
SECONDARY Number of Participants With a Radiological Progression Event-Free - Three Dose Groups as Randomized	77; 77; 90	—
SECONDARY Radiological Progression Free Survival - Three Dose Groups as Randomized	6.3; 7.5; 6.1	—
SECONDARY Number of Participants With a Radiological Progression Event - High Dose vs. Standard Dose	63; 115	—
SECONDARY Time to Radiological Progression - High Dose vs. Standard Dose	8.7; 6.2	0.9274
SECONDARY Number of Participants With a Radiological Progression Event - Extended Dose vs. Standard Dose	43; 43	—
SECONDARY Time to Radiological Progression - Extended Dose vs. Standard Dose	8.9; 9.0	0.5754
SECONDARY Number of Participants With a Radiological Progression Event - Three Dose Groups as Randomized	66; 63; 67	—
SECONDARY Time to Radiological Progression - Three Dose Groups as Randomized	6.2; 8.7; 6.6	—
SECONDARY Timepoint Pain Improvement Rate - Three Dose Groups as Randomized	16.7; 16.0; 18.6; 27.1; 26.0; 37.2	—
SECONDARY Timepoint Pain Improvement Rate - Extended Dose vs. Standard Dose	31.8; 30.0; 40.9; 55.0	—
SECONDARY Number of Participants With a Pain Progression Event - High Dose vs. Standard Dose	31; 68	—
SECONDARY Time to Pain Progression - High Dose vs. Standard Dose	NA; NA	0.6214
SECONDARY Number of Participants With a Pain Progression Event - Extended Dose vs. Standard Dose	10; 15	—
SECONDARY Time to Pain Progression - Extended Dose vs. Standard Dose	NA; NA	0.7214
SECONDARY Number of Participants With a Pain Progression Event - Three Dose Groups as Randomized	32; 31; 46	—
SECONDARY Time to Pain Progression - Three Dose Groups as Randomized	NA; NA; 10.1	—
SECONDARY Number of Participants With Treatment-Emergent Adverse Events	118; 119; 116; 23; 20; 18	—

Summary

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.

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02023697). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.