The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02605356




Registration number
NCT02605356
Ethics application status
Date submitted
12/11/2015
Date registered
16/11/2015
Date last updated
7/10/2016

Titles & IDs
Public title
Phase 1b/2 Study Testing Radium-223 Dichloride/Bortezomib/Dexamethasone Combination in Relapsed Multiple Myeloma
Scientific title
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
Secondary ID [1] 0 0
2015-000427-82
Secondary ID [2] 0 0
17451
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Radium-223 dichloride (Xofigo, BAY88-8223)
Treatment: Drugs - Placebo
Treatment: Drugs - Bortezomib
Treatment: Drugs - Dexamethasone

Experimental: Radium-223 dichloride [Phase 1, dose 1] - 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.

Experimental: Radium-223 dichloride [Phase 1, dose 2] - 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.

Experimental: Radium-223 dichloride [Phase 1, dose 3] - 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.

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

Experimental: Radium-223 dichloride + SoC [Phase 2] - Phase 2: Phase 1b-selected dose of radium-223 dichloride every 4 weeks for 6 doses plus SOC bortezomib/dexamethasone


Treatment: Drugs: Radium-223 dichloride (Xofigo, BAY88-8223)


Treatment: Drugs: Placebo


Treatment: Drugs: Bortezomib


Treatment: Drugs: Dexamethasone


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Joint positive adjudication of safety summary in Phase 1b by steering committee, investigator and sponsor (Yes/No)
Timepoint [1] 0 0
At 13 months
Primary outcome [2] 0 0
Progression-free survival (PFS) in Phase 2, defined as the time (in days) from date of randomization to disease progression
Timepoint [2] 0 0
Up to 25 months
Secondary outcome [1] 0 0
Objective response rate (ORR) in Phase 1b, in the proportion of subjects in the analysis population who have complete response (CR), stringent complete response (sCR), very good partial response (VGPR), partial response (PR), or stable disease (SD)
Timepoint [1] 0 0
Approximately 12 months
Secondary outcome [2] 0 0
Duration of response in Phase 1b, defined as the time (in days) from the date of first response to treatment (CR, sCR, VGPR, PR) to the date of disease progression or death
Timepoint [2] 0 0
Approximately 12 months
Secondary outcome [3] 0 0
Number of participants with adverse events in phase 2
Timepoint [3] 0 0
Up to 25 months
Secondary outcome [4] 0 0
Overall survival (OS) in Phase 2, defined as the time (in days) from date of randomization until death from any cause
Timepoint [4] 0 0
Up to 25 months
Secondary outcome [5] 0 0
Time to Symptomatic Skeletal Event (SSE) in Phase 2, defined as the time (days) from the date of randomization to the date of the first on-study SSE
Timepoint [5] 0 0
Up to 25 months
Secondary outcome [6] 0 0
Symptomatic skeletal event free survival in Phase 2, defined as the time from randomization to the occurrence of 1 of the following: First on-study SSE or Death from any cause if death occurs before a documented SSE
Timepoint [6] 0 0
Up to 25 months
Secondary outcome [7] 0 0
Time to pain progression in Phase 2
Timepoint [7] 0 0
Up to 25 months
Secondary outcome [8] 0 0
Duration of response in Phase 2
Timepoint [8] 0 0
Up to 25 months
Secondary outcome [9] 0 0
Objective Response Rate (ORR) in Phase 2
Timepoint [9] 0 0
Up to 25 months

Eligibility
Key inclusion criteria
- Cytologically or histologically confirmed diagnosis of multiple myeloma

- Subjects must have received at least 1 and not more than 3 previous lines of treatment
and have had a response to treatment (i.e., achieved a minimal response [MR] or
better) according to the International Myeloma Working Group (IMWG) uniform response
criteria

- Subjects must have had progressive disease according to the IMWG uniform response
criteria following the last multiple myeloma treatment

- Subjects must have measurable disease defined as at least 1 of the following
(according to central laboratory results):

- Serum M-protein =1 g/dL

- Urine M-protein =200 mg/24 hours

- Serum free light chain (FLC) =10 mg/dL with abnormal ratio

- =1 bone lesion identifiable by radiograph, computed tomography, magnetic resonance
imaging, or bone scintigraphy

- Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2

- Subjects must be nonrefractory to bortezomib and had no progression during or within
60 days after completion of bortezomib

- Absolute neutrophil count (ANC) =1.5 × 10e9/L, hemoglobin (Hb) =9.0 g/dL, and platelet
count =75.0 × 10e9/L independent of transfusion of red blood cells (RBC) or platelet
concentrates and independent of granulocyte colony stimulating factor (G-CSF) or
granulocyte macrophage colony stimulating factor (GM-CSF)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Systemic glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within
the last 4 weeks prior to first dose, unless tapered and on a stable dose =10 mg/day
for at least 1 week

- Subjects with known POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy,
monoclonal protein, and skin changes) or light chain (AL) amyloidosis

- Plasma cell leukemia

- Systemic anti-cancer therapy within 4 weeks prior to first dose

- Radiation therapy in the previous 4 weeks prior to first dose except if given for pain
management and involves less than 10% of the bone marrow

- Prior treatment with radium-223 dichloride or any experimental radiopharmaceutical

- Congestive heart failure (New York Heart Association [NYHA] class III to IV),
symptomatic cardiac ischemia, cardiomyopathy, clinically relevant ventricular
arrhythmia, pericardial disease, unstable angina or myocardial infarct in the previous
6 months prior to first dose, left ventricular ejection fraction <40%

- Neuropathy = Grade 2 or Grade 1 with pain

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Box Hill
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
South Dakota
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Belgium
State/province [10] 0 0
Brugge
Country [11] 0 0
Belgium
State/province [11] 0 0
Bruxelles - Brussel
Country [12] 0 0
Belgium
State/province [12] 0 0
Liege
Country [13] 0 0
Belgium
State/province [13] 0 0
Yvoir
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Germany
State/province [15] 0 0
Baden-Württemberg
Country [16] 0 0
Germany
State/province [16] 0 0
Bayern
Country [17] 0 0
Germany
State/province [17] 0 0
Rheinland-Pfalz
Country [18] 0 0
Germany
State/province [18] 0 0
Berlin
Country [19] 0 0
Greece
State/province [19] 0 0
Athens
Country [20] 0 0
Greece
State/province [20] 0 0
Rio / Patra
Country [21] 0 0
Israel
State/province [21] 0 0
Afula
Country [22] 0 0
Israel
State/province [22] 0 0
Haifa
Country [23] 0 0
Israel
State/province [23] 0 0
Jerusalem
Country [24] 0 0
Israel
State/province [24] 0 0
Ramat Gan
Country [25] 0 0
Israel
State/province [25] 0 0
Zerifin
Country [26] 0 0
Italy
State/province [26] 0 0
Emilia-Romagna
Country [27] 0 0
Italy
State/province [27] 0 0
Lombardia
Country [28] 0 0
Italy
State/province [28] 0 0
Piemonte
Country [29] 0 0
Italy
State/province [29] 0 0
Sardegna
Country [30] 0 0
Italy
State/province [30] 0 0
Toscana
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Gyeonggido
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Daegu
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Jeollanam-do
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul
Country [35] 0 0
Spain
State/province [35] 0 0
Barcelona
Country [36] 0 0
Spain
State/province [36] 0 0
Guipúzcoa
Country [37] 0 0
Spain
State/province [37] 0 0
Illes Baleares
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
Spain
State/province [39] 0 0
Sevilla
Country [40] 0 0
Spain
State/province [40] 0 0
Valencia
Country [41] 0 0
Taiwan
State/province [41] 0 0
Taichung
Country [42] 0 0
Taiwan
State/province [42] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02605356
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02605356