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Phase 1: Radium-223 dichloride; 30 kiloBecquerel (kBq)/kg body weight (33 kBq/kg after implementation of National Institute of Standards and Technology \[NIST\] update) every 4 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.

Phase 1: Radium-223 dichloride; 50 kBq/kg body weight (55 kBq/kg after implementation of NIST update) every 4 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.

Phase 1: Radium-223 dichloride; 80 kBq/kg body weight (88 kBq/kg after implementation of NIST update) every 4 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/dexamethasone.

Phase 2: Matching placebo (isotonic saline) every 4 weeks for a total of 6 doses plus SoC (Standard of care) bortezomib/dexamethasone.

Phase 2: Phase 1b-selected dose of radium-223 dichloride every 4 weeks for 6 doses plus SOC bortezomib/dexamethasone

Radium-223 dichloride (Xofigo, BAY88-8223)

Placebo

Bayer Study Director

This study will be conducted in 2 parts. The phase 1b part will be an international, phase 1b, open-label, dose-escalation assessment of radium-223 dichloride administered with bortezomib and dexamethasone in subjects with relapsed multiple myeloma. The primary endpoint of the phase 1b part is to determine the optimal dose of radium-223 dichloride in combination with bortezomib/dexamethasone for the Phase 2 portion of the study.

The phase 2 part will be an international, phase 2, double-blind, randomized, placebo-controlled assessment of radium-223 dichloride versus placebo administered with bortezomib and dexamethasone, in subjects with relapsed multiple myeloma. Randomization (1:1) in the phase 2 part will be stratified by:

* Prior bortezomib treatment (yes, no)
* Prior treatment (1 prior line of treatment, \>1 prior line of treatment) Approximately 30 subjects (10 subjects per cohort) will be enrolled in the phase 1b part of the study and approximately 196 subjects will be enrolled in the phase 2 part of the study.

Phase 1b/2 Study Testing Radium-223 Dichloride/Bortezomib/Dexamethasone Combination in Relapsed Multiple Myeloma

A Phase 1b/2 Trial to Evaluate the Safety and Efficacy of Radium-223 Dichloride (BAY88-8223) in Combination With Bortezomib and Dexamethasone in Early Relapsed Multiple Myeloma

Bayer

Phase 1: Radium-223 dichloride; 33 kiloBecquerel (kBq)/kg body weight every 6 weeks for a total of 6 radium-223 dichloride doses plus SOC (standard of care) bortezomib/ dexamethasone.

Phase 1: Radium-223 dichloride; 55 kBq/kg body weight every 6 weeks for a total of 6 radium-223 dichloride doses plus SOC bortezomib/ dexamethasone.

Phase 2: Matching placebo (isotonic saline) every 6 weeks for a total of 6 doses plus SOC bortezomib/dexamethasone.

Phase 2: Phase 1b-selected dose of radium-223 dichloride every 6 weeks for 6 doses plus SOC bortezomib/dexamethasone

Sequential dose escalation in Intravenous (IV) injection

Bortezomib is administered subcutaneous (SC) (per Investigator choice ) at 1.3 mg/m2/dose

Dexamethasone is administered orally at 40 mg

This study will be conducted in 2 parts. The phase 1b part will be an international, phase 1b, open-label, dose-escalation assessment of radium-223 dichloride administered with bortezomib and dexamethasone in subjects with relapsed multiple myeloma. The primary endpoint is to determine the optimal dose of radium-223 dichloride in combination with bortezomib/dexamethasone for the Phase 2 portion of the study.

The phase 2 part will be an international, phase 2, double-blind, randomized, placebo-controlled assessment of radium-223 dichloride versus placebo administered with bortezomib and dexamethasone, in subjects with relapsed multiple myeloma.

Up to 12 subjects in all dose cohorts combined will be treated in the phase 1b part of the study. Up to approximately 100 subjects will be enrolled in the phase 2 part of the study.

Study Testing Radium-223 Dichloride in Relapsed Multiple Myeloma

Maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) determined by incidence of dose limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for the severity grade

A treatment-emergent adverse event (TEAE) is defined as any event arising or worsening after start of study drug administration until the end of the treatment period

Determined by International Myeloma Working Group (IMWG) uniform response criteria.

CR: Negative immunofixation of serum and urine, disappearance of any soft-tissue plasmacytomas, and \<5% plasma cells in bone marrow; in patients for whom only measurable disease is by serum free light chain (FLC) level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria is required; 2 consecutive assessments are needed.

VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-component plus urine M-component \<100 mg/24 hours (hrs); in patients for whom only measurable disease is by serum FLC level, \>90% decrease in difference between involved and uninvolved FLC levels, in addition to VGPR criteria, is required; 2 consecutive assessments are needed

Subjects received 33 kiloBecquerel (kBq)/kg body weight every 6 weeks for a total of 6 radium-223dichloride doses in combination with BOR and DEX

Radium-223 33 kBq/kg + BOR/DEX

Subjects received 55 kBq/kg body weight every 6 weeks for a total of 6 radium-223dichloride doses in combination with BOR and DEX

Radium-223 55 kBq/kg + BOR/DEX

Participants received 33 kiloBecquerel (kBq)/kg body weight every 6 weeks for a total of 6 radium-223 dichloride doses in combination with BOR and DEX

Radium-223 Dichloride 33 kBq/kg + Bortezomib and Dexamethasone

Participants received 55 kBq/kg body weight every 6 weeks for a total of 6 radium-223 dichloride doses in combination with BOR and DEX

Radium-223 Dichloride 55 kBq/kg + Bortezomib and Dexamethasone

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Safety population included all randomized subjects who received at least one administration of study treatment

Therapeutic Area Head

The safety analysis set including all participants who received at least one administration of study treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1b/2 Study Testing Radium-223 Dichloride/Bortezomib/Dexamethasone Combination in Relapsed Multiple Myeloma	NCT02605356	Multiple Myelom...	Radium-223 dich... Placebo Bortezomib Dexamethasone	18 Years -	Bayer
Study Testing Radium-223 Dichloride in Relapsed Multiple Myeloma	NCT02928029	Multiple Myelom...	Radium-223 dich... Placebo Bortezomib Dexamethasone	18 Years -	Bayer
Study Testing Radium-223 Dichloride in Relapsed Multiple Myeloma	NCT02928029	Multiple Myelom...	Radium-223 dich... Placebo Bortezomib Dexamethasone	18 Years -	Bayer
Study Testing Radium-223 Dichloride in Relapsed Multiple Myeloma	NCT02928029	Multiple Myelom...	Radium-223 dich... Placebo Bortezomib Dexamethasone	18 Years -	Bayer

Spots Global Cancer Trial Database for combination therapy multiple myeloma