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

NCT ID: NCT02605356

Last Updated: 2016-10-07

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2021-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Radium-223 dichloride (Xofigo, BAY88-8223)

Intervention Type: DRUG

Bortezomib

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

Radium-223 dichloride (Xofigo, BAY88-8223)

Intervention Type: DRUG

Bortezomib

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

Radium-223 dichloride (Xofigo, BAY88-8223)

Intervention Type: DRUG

Bortezomib

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Bortezomib

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Radium-223 dichloride (Xofigo, BAY88-8223)

Intervention Type: DRUG

Bortezomib

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Interventions

Radium-223 dichloride (Xofigo, BAY88-8223)

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Bortezomib

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Eligibility Criteria

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)

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Scottsdale, Arizona, United States

Little Rock, Arkansas, United States

Encinitas, California, United States

Metairie, Louisiana, United States

Rockville, Maryland, United States

New York, New York, United States

Durham, North Carolina, United States

Winston-Salem, North Carolina, United States

Watertown, South Dakota, United States

Seattle, Washington, United States

Adelaide, South Australia, Australia

Box Hill, , Australia

Bruges, , Belgium

Bruxelles - Brussel, , Belgium

Bruxelles - Brussel, , Belgium

Liège, , Belgium

Yvoir, , Belgium

Québec, Quebec, Canada

Tübingen, Baden-Wurttemberg, Germany

München, Bavaria, Germany

Mainz, Rhineland-Palatinate, Germany

Berlin, State of Berlin, Germany

Athens, , Greece

Rio / Patra, , Greece

Afula, , Israel

Haifa, , Israel

Jerusalem, , Israel

Ramat Gan, , Israel

Ẕerifin, , Israel

Bologna, Emilia-Romagna, Italy

Reggio Emilia, Emilia-Romagna, Italy

Milan, Lombardy, Italy

Milan, Lombardy, Italy

Novara, Piedmont, Italy

Turin, Piedmont, Italy

Cagliari, Sardinia, Italy

Florence, Tuscany, Italy

Pisa, Tuscany, Italy

Goyang-si, Gyeonggido, South Korea

Daegu, , South Korea

Jeollanam-do, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Badalona, Barcelona, Spain

Barcelona, Barcelona, Spain

San Sebastián, Guipúzcoa, Spain

Palma de Mallorca, Illes Baleares, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Seville, Sevilla, Spain

Valencia, Valencia, Spain

Barcelona, , Spain

Taipei, Taipei, Taiwan

Taichung, , Taiwan

Taipei, , Taiwan

Taipei, , Taiwan

Countries

United States; Australia; Belgium; Canada; Germany; Greece; Israel; Italy; South Korea; Spain; Taiwan

Other Identifiers

2015-000427-82

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17451

Identifier Type: -

Identifier Source: org_study_id