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Study Testing Radium-223 Dichloride in Relapsed Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT02928029
Recruitment Status : Recruiting
First Posted : October 7, 2016
Last Update Posted : November 22, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

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 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.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Radium-223 dichloride (Xofigo, BAY88-8223) Drug: Placebo Drug: Bortezomib Drug: Dexamethasone Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : February 10, 2017
Estimated Primary Completion Date : December 4, 2021
Estimated Study Completion Date : January 3, 2022


Arm Intervention/treatment
Experimental: Phase1, arm1: Radium-223 dichloride+SOC
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.
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Sequential dose escalation in Intravenous (IV) injection

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

Drug: Dexamethasone
Dexamethasone is administered orally at 40 mg

Experimental: Phase1, arm2: Radium-223 dichloride+SOC
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.
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Sequential dose escalation in Intravenous (IV) injection

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

Drug: Dexamethasone
Dexamethasone is administered orally at 40 mg

Placebo Comparator: Phase2, arm1: Placebo+SOC
Phase 2: Matching placebo (isotonic saline) every 6 weeks for a total of 6 doses plus SOC bortezomib/dexamethasone.
Drug: Placebo
Matching placebo

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

Drug: Dexamethasone
Dexamethasone is administered orally at 40 mg

Experimental: Phase2, arm2: Radium-223 dichloride+SOC
Phase 2: Phase 1b-selected dose of radium-223 dichloride every 6 weeks for 6 doses plus SOC bortezomib/dexamethasone
Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
Sequential dose escalation in Intravenous (IV) injection

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

Drug: Dexamethasone
Dexamethasone is administered orally at 40 mg




Primary Outcome Measures :
  1. Phase 1: Number of subjects with dose-limiting toxicities treated with radium-223 dichloride in combination with BOR/DEX [ Time Frame: Up to 13 months ]
  2. Phase 1: Maximum tolerated dose/ recommended phase-2 dose of radium-223 dichloride in combination with BOR/DEX [ Time Frame: Up to 13 months ]
  3. Phase 1: Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 36 months ]
  4. Phase 1: Incidence of drug-related TEAEs [ Time Frame: Up to 36 months ]
  5. Phase 1: Incidence of serious adverse events [ Time Frame: Up to 36 months ]
  6. Phase 2: Combined CR+VGPR rate [ Time Frame: Up to 36 months ]
    Combined rate of Complete Response (CR) and Very Good Partial Response (VGPR) according to IMWG uniform response criteria.


Secondary Outcome Measures :
  1. Phase 1: Combined CR+VGPR rate [ Time Frame: Up to 36 months ]
    Combined rate of Complete Response (CR) and Very Good Partial Response (VGPR) according to IMWG uniform response criteria.

  2. Phase 2: Number of subjects with adverse events [ Time Frame: Up to 36 months ]
  3. Phase 2: Objective response rate (ORR) [ Time Frame: Up to 36 months ]
    Defined as the proportion of subjects in the analysis population who have Complete Response (CR), Partial Response (PR) and Very Good Partial Response (VGPR) during the course of the study according to IMWG uniform response criteria.

  4. Phase 2: Overall survival (OS) [ Time Frame: Up to 36 months ]
    Defined as the time (in months) from date of randomization until death.

  5. Phase 2: Progression-free survival (PFS) [ Time Frame: Up to 36 months ]
    Defined as the time (in months) from the date of randomization to the date of disease progression or death, whichever occurs first.

  6. Phase 2. Duration of response (DOR) [ Time Frame: Up to 36 months ]
    Defined as the time (in months) from the date of first response to treatment (Complete Response, Very Good Partial Response or Partial Response) to the date of disease progression or death. Duration of response is only applied to subjects with a disease response of at least Partial Response.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must have documented monoclonal plasma cells in the bone marrow of ≥10%, as defined by their institutional standard at some point in their disease history or the presence of a biopsy proven plasmacytoma.
  • Subjects must have received at least 1 and not more than 3 previous lines of treatment and have had a response to at least 1 prior Treatment in the past (i.e., achieved a minimal response [MR] or better) according to the IMWG uniform response criteria.
  • Subject must be non-refractory to bortezomib (Refractory is defined: progression of disease while receiving bortezomib therapy or within 60 days of ending bortezomib therapy).
  • Subjects must have documented evidence of 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:

    • Serum M-protein defined by the following:

      • IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL (measured by protein electrophoresis [PEP]);
      • IgA, IgD, IgE, IgM multiple myeloma: serum M-protein level ≥0.5 g/dL (measured by PEP).
    • Urine M-protein ≥200 mg/24 hours (any immunoglobulin heavy chain type measured by PEP).
    • Serum free light chain (FLC) ≥10 mg/dL with abnormal ratio in subjects with unmeasurable disease by serum or urine PEP.
  • ≥1 bone lesion identifiable by radiograph, computed tomography (CT), positron emission tomography - computed tomography (PET-CT), or magnetic resonance imaging (MRI).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
  • Adequate hepatic function, with total bilirubin ≤1.5 x upper limit of normal (ULN) (except for Gilbert Syndrome: total bilirubin < 3.0 x ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x ULN.
  • 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).
  • International normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x ULN. Prothrombin time (PT) may be used instead of INR if ≤ 1.5 x ULN.

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 (prednisone ≤10 mg/day orally or equivalent) 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 (defined by plasma cell >20%, and/or an absolute plasma cell count of >2 x 10e9/L in peripheral blood).
  • Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic (PK) half-lives (t1/2) of the treatment, whichever is longer, before the date of start of treatment.
  • Radiation therapy in the previous 4 weeks prior to first dose.
  • 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, unstable angina or myocardial infarction in the previous 6 months prior to first dose, or with a known left ventricular ejection fraction (LVEF) <40%, cardiomyopathy, pericardial disease, clinically relevant cardiac arrhythmia (CTCAE version 4.03 Grade 2 or higher), clinically significant ECG abnormalities, or screening 12-lead ECG showing a baseline prolonged QT interval (baseline QT interval as corrected by Fridericia's formula > 470 msec).
  • Neuropathy ≥ Grade 2.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02928029


Contacts
Contact: Bayer Clinical Trials Contact (+)1-888-84 22937 clinical-trials-contact@bayer.com

Locations
United States, California
Pacific Oncology/Hematology Associates Recruiting
Encinitas, California, United States, 92024
California Cancer Associates for Research & Excellence, Inc. Not yet recruiting
Fresno, California, United States, 93720
United States, New York
Columbia University Not yet recruiting
New York, New York, United States, 10032-3729
United States, North Carolina
Wake Forest Baptist Health Recruiting
Winston-Salem, North Carolina, United States, 27157
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109-4417
Korea, Republic of
National Cancer Center Recruiting
Goyang-si, Gyeonggido, Korea, Republic of, 410-769
Chonnam National University Hwasun Hospital Not yet recruiting
Hwasun, Jeollanam-do, Korea, Republic of, 519-763
Kyungpook National University Hospital Not yet recruiting
Daegu, Korea, Republic of, 41404
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Asan Medical Center Not yet recruiting
Seoul, Korea, Republic of, 05505
Samsung Medical Center Not yet recruiting
Seoul, Korea, Republic of, 06351
Seoul St. Mary's Hospital Not yet recruiting
Seoul, Korea, Republic of, 06591
Spain
Institut Català d'Oncologia Badalona Not yet recruiting
Badalona, Barcelona, Spain, 08916
Hospital Universitari Son Espases Recruiting
Palma de Mallorca, Illes Baleares, Spain, 07120
Ciutat Sanitària i Universitaria de la Vall d'Hebron Not yet recruiting
Barcelona, Spain, 08035
Hospital Universitario de la Princesa Not yet recruiting
Madrid, Spain, 28006
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain, 41013
Hospital Universitario Dr. Peset Not yet recruiting
Valencia, Spain, 46017
Sponsors and Collaborators
Bayer

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02928029     History of Changes
Other Study ID Numbers: 18987
2016-002438-58 ( EudraCT Number )
First Posted: October 7, 2016    Key Record Dates
Last Update Posted: November 22, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
Radium-223 dichloride
Bortezomib
Dexamethasone
Relapsed multiple myeloma
Combination therapy multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Radium Ra 223 dichloride
Bortezomib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents