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

NCT02605356 | Withdrawn Phase 1 DMC

• 2 other identifiers: 174512015-000427-82
• Study Type: interventional
• Target: N/A
• Locations: 11 countries
• Sites: 58

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.

Conditions

Multiple Myeloma

Keywords

Radium-223 dichloride; bortezomib; dexamethasone; early relapsed multiple myeloma; combination therapy multiple myeloma

Outcome Measures

Primary Outcomes (2)

• Joint positive adjudication of safety summary in Phase 1b by steering committee, investigator and sponsor (Yes/No)

  At 13 months

• Progression-free survival (PFS) in Phase 2, defined as the time (in days) from date of randomization to disease progression

  Up to 25 months

Secondary Outcomes (9)

• 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)

  Approximately 12 months

• 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

  Approximately 12 months

• Number of participants with adverse events in phase 2

  Up to 25 months

• Overall survival (OS) in Phase 2, defined as the time (in days) from date of randomization until death from any cause

  Up to 25 months

• 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

  Up to 25 months

Study Arms (5)

Radium-223 dichloride [Phase 1, dose 1]

EXPERIMENTAL

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.

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

Radium-223 dichloride [Phase 1, dose 2]

EXPERIMENTAL

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.

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

Radium-223 dichloride [Phase 1, dose 3]

EXPERIMENTAL

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.

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

Placebo +SoC [Phase 2]

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Bortezomib; Drug: Dexamethasone

Radium-223 dichloride + SoC [Phase 2]

EXPERIMENTAL

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

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

Interventions

Radium-223 dichloride (Xofigo, BAY88-8223) DRUG

Radium-223 dichloride + SoC [Phase 2]; Radium-223 dichloride [Phase 1, dose 1]; Radium-223 dichloride [Phase 1, dose 2]; Radium-223 dichloride [Phase 1, dose 3]

Placebo DRUG

Placebo +SoC [Phase 2]

Bortezomib DRUG

Placebo +SoC [Phase 2]; Radium-223 dichloride + SoC [Phase 2]; Radium-223 dichloride [Phase 1, dose 1]; Radium-223 dichloride [Phase 1, dose 2]; Radium-223 dichloride [Phase 1, dose 3]

Dexamethasone DRUG

Placebo +SoC [Phase 2]; Radium-223 dichloride + SoC [Phase 2]; Radium-223 dichloride [Phase 1, dose 1]; Radium-223 dichloride [Phase 1, dose 2]; Radium-223 dichloride [Phase 1, dose 3]

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (58)

Unknown Facility

Scottsdale, Arizona, 85259-5404, United States

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Little Rock, Arkansas, 72205, United States

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Encinitas, California, 92024, United States

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Metairie, Louisiana, 70006, United States

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Rockville, Maryland, 20850-6535, United States

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New York, New York, 10032-3729, United States

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Durham, North Carolina, 27710, United States

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Winston-Salem, North Carolina, 27157, United States

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Watertown, South Dakota, 57201, United States

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Seattle, Washington, 98104, United States

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Adelaide, South Australia, 5000, Australia

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Box Hill, 3128, Australia

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Bruges, 8000, Belgium

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Bruxelles - Brussel, 1090, Belgium

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Bruxelles - Brussel, 1200, Belgium

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Liège, 4000, Belgium

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Yvoir, 5530, Belgium

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Québec, Quebec, G1R 2J6, Canada

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Tübingen, Baden-Wurttemberg, 72076, Germany

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München, Bavaria, 81377, Germany

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Mainz, Rhineland-Palatinate, 55131, Germany

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Berlin, State of Berlin, 12203, Germany

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Athens, 11528, Greece

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Rio / Patra, 26500, Greece

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Afula, 1834111, Israel

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Haifa, 31048, Israel

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Jerusalem, 9112001, Israel

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Ramat Gan, 5262000, Israel

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Ẕerifin, 6093000, Israel

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Bologna, Emilia-Romagna, 40138, Italy

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Reggio Emilia, Emilia-Romagna, 42123, Italy

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Milan, Lombardy, 20089, Italy

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Milan, Lombardy, 20132, Italy

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Novara, Piedmont, 28100, Italy

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Turin, Piedmont, 10126, Italy

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Cagliari, Sardinia, 09121, Italy

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Florence, Tuscany, 50141, Italy

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Pisa, Tuscany, 56126, Italy

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Goyang-si, Gyeonggido, 410-769, South Korea

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Daegu, 700-701, South Korea

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Jeollanam-do, 519-763, South Korea

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Seoul, 03080, South Korea

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Seoul, 135-710, South Korea

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Seoul, 137-701, South Korea

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Seoul, 138-736, South Korea

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Badalona, Barcelona, 08916, Spain

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Barcelona, Barcelona, 08036, Spain

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San Sebastián, Guipúzcoa, 20014, Spain

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Palma de Mallorca, Illes Baleares, 07010, Spain

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Madrid, Madrid, 28006, Spain

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Madrid, Madrid, 28046, Spain

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Seville, Sevilla, 41013, Spain

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Valencia, Valencia, 46017, Spain

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Barcelona, 08035, Spain

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Taipei, Taipei, 10016, Taiwan

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Taichung, 40447, Taiwan

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Taipei, 11217, Taiwan

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Taipei, Taiwan

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MeSH Terms

Conditions

Multiple Myeloma

Interventions

radium Ra 223 dichloride; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2015
• First Posted: November 16, 2015
• Study Start: October 1, 2016
• Primary Completion: November 1, 2019
• Study Completion: July 1, 2021
• Last Updated: October 7, 2016

Record last verified: 2016-09

Locations

CA (1); IT (9); KR (7); ES (9); AU (2); TW (4); BE (5); US (10); GR (2); DE (4); IL (5)