Study of Radium-223 Dichloride Versus Placebo and Hormonal Treatment as Background Therapy in Subjects With Bone Predominant HER2 (Human Epidermal Growth Factor Receptor 2) Negative Hormone Receptor Positive Metastatic Breast Cancer

NCT02258464 | Terminated Phase 2 Results DMC

• 2 other identifiers: 162982014-002113-39
• Study Type: interventional
• Target: 99
• Locations: 20 countries
• Sites: 71

Brief Summary

The objective of this study was to assess efficacy and safety of radium-223 dichloride in subjects with human epidermal growth factor receptor 2 negative (HER2 negative) hormone receptor positive breast cancer with bone metastases treated with hormonal treatment background therapy

Conditions

Breast Neoplasms

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Symptomatic Skeletal Event Free Survival (SSE-FS)

  Time from date of randomization to occurrence of one of the following, whichever happened earlier: 1) an on study SSE, which was defined as the use of external beam radiotherapy (EBRT) to relieve skeletal symptoms, the occurrence of new symptomatic pathological bone fractures (vertebral or nonvertebral), the occurrence of spinal cord compression, a tumor related orthopedic surgical intervention; or 2) death from any cause

  Up to approximately 51 months

Secondary Outcomes (8)

• Overall Survival

  Up to approximately 51 months

• Time to Opiate Use for Cancer Pain

  Up to approximately 51 months

• Time to Pain Progression

  Up to approximately 51 months

• Pain Improvement Rate

  Up to approximately 51 months

• Time to Cytotoxic Chemotherapy

  Up to approximately 51 months

Study Arms (2)

Radium 223 dichloride

EXPERIMENTAL

Participants treated with a single hormonal agent as background therapy received 50 kBq/kg body weight (55 kBq/kg after implementation of National Institute of Standards and Technology \[NIST\] update) of Radium 223 dichloride intravenously for a maximum of 6 cycles at intervals of 4 weeks

Drug: Radium-223 dichloride (Xofigo, BAY88-8223); Other: Background hormonal therapy

Placebo

PLACEBO COMPARATOR

Participants treated with a single hormonal agent as background therapy received isotonic saline (0.9% sodium chloride solution for injection) intravenously for a maximum of 6 cycles at intervals of 4 weeks

Drug: Placebo (saline); Other: Background hormonal therapy

Interventions

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

Up to 6 cycles of radium-223 dichloride 50kBq/kg body (55 kBq/kg after implementation of National Institute of Standards and Technology \[NIST\] update)

Radium 223 dichloride

Placebo (saline) DRUG

Up to 6 cycles of saline injection

Placebo

Background hormonal therapy OTHER

Prescribed by PI and was provided as long as patient can tolerate treatment. It must be prescribed as per local label in country participating.

Placebo; Radium 223 dichloride

Eligibility Criteria

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

You may qualify if:

• Documentation of histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative adenocarcinoma of the breast must be available.
• Women (≥18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy.
• Documentation of menopausal status: post menopausal or premenopausal subjects are eligible.
• Subjects with bone dominant disease with at least 2 skeletal metastases identified at baseline by bone scintigraphy and confirmed by CT/magnetic resonance imaging (MRI). Presence of metastases in soft tissue (skin, subcutaneous, muscle, fat, lymph nodes)and/or visceral metastases is allowed.
• Measurable or non-measurable disease (but radiologically evaluable) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
• Subjects must have received at least one line of hormonal therapy in the metastatic setting
• Subjects who are eligible for further standard of care endocrine treatment.
• Subjects enrolled in the current study must start treatment with the single hormone agent either within 15 days prior to randomization or after randomization (before or simultaneously to the first injection of Ra-223/placebo).
• Subjects must have experienced no more than two skeletal-related events (SREs) prior to study entry defined as: Need for external beam radiotherapy (EBRT) tor bone, pathological bone fracture (excluding major trauma), spinal cord compression and/or orthopedic surgical procedure. Subjects with no prior SREs are not permitted.
• Subjects must be on therapy with bisphosphonate and denosumab. and are required to have been on such therapy for at least 1 month before start of study treatment.
• Adequate hematological, liver and kidney function.

You may not qualify if:

• Subjects with Inflammatory breast cancer.
• Subjects who have either received chemotherapy for metastatic disease or are considered by the treating investigator to be appropriate candidates for chemotherapy as current treatment for metastatic breast cancer are excluded. Chemotherapy administered for adjuvant/neo adjuvant disease is acceptable.
• Subjects with known or history of brain metastases or leptomeningeal disease: subjects with neurological symptoms must undergo a contrast CT scan or MRI of the brain within 28 days prior to randomization to exclude active brain metastasis. Imaging of the central nervous system (CNS) is otherwise not required.
• Known presence of osteonecrosis of jaw.
• Patients with immediately life-threatening visceral disease, for whom chemotherapy is the preferred treatment option.
• Lymphangitic carcinomatosis.
• Patients with ascites requiring paracentesis within 2 weeks prior to study entry (signature of informed consent) and during the screening period.

Sponsors & Collaborators

• Bayer: lead

Study Sites (71)

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Bakersfield, California, 93309, United States

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La Jolla, California, 92093, United States

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Aurora, Colorado, 80045, United States

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New Haven, Connecticut, 06520, United States

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Cedar Rapids, Iowa, 52403, United States

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Annapolis, Maryland, 21401, United States

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Ann Arbor, Michigan, 48109, United States

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Pontiac, Michigan, 48341, United States

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St Louis, Missouri, 63110, United States

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Pittsburgh, Pennsylvania, 15213-3180, United States

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Houston, Texas, 77230, United States

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Linz, Upper Austria, 4020, Austria

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Innsbruck, 6020, Austria

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Winnipeg, Manitoba, R3E 0V9, Canada

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London, Ontario, N6A 4L6, Canada

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Newmarket, Ontario, L3Y 2P9, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Ostrava, 708 52, Czechia

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Prague, 12808, Czechia

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Copenhagen, 2100, Denmark

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Herlev, 2730, Denmark

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Helsinki, 00290, Finland

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Tampere, FIN-33520, Finland

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Angers, 49055, France

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Saint-Cloud, 92210, France

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Tübingen, Baden-Wurttemberg, 72076, Germany

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Bonn, North Rhine-Westphalia, 53105, Germany

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Essen, North Rhine-Westphalia, 45147, Germany

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Kowloon, Hong Kong

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Cork, Ireland

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Dublin, 7, Ireland

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Afula, 1834111, Israel

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Haifa, 3109601, Israel

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Jerusalem, 9103102, Israel

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Jerusalem, 9112001, Israel

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Kfar Saba, 4428164, Israel

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Ramat Gan, 5262000, Israel

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Tel Aviv, 64239, Israel

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Ẕerifin, 7030000, Israel

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Nieuwegein, 3435 CM, Netherlands

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Zwolle, 8025 AB, Netherlands

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Oslo, 0424, Norway

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Bialystok, 15-027, Poland

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Gdynia, 81-519, Poland

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Warsaw, 02-781, Poland

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Singapore, 119074, Singapore

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Busan, 49241, South Korea

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Daegu, 42601, South Korea

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Incheon, South Korea

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Seoul, 03080, South Korea

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Seoul, 05505, South Korea

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Seoul, 120-752, South Korea

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L'Hospitalet de Llobregat, Barcelona, 08907, Spain

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A Coruña, 15009, Spain

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Barcelona, 08025, Spain

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Barcelona, 08036, Spain

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Madrid, 28033, Spain

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Madrid, 28040, Spain

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Madrid, 28041, Spain

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Málaga, 29010, Spain

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Seville, 41071, Spain

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Zaragoza, 50009, Spain

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Aarau, Canton of Aargau, 5001, Switzerland

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Taipei, 11217, Taiwan

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Plymouth, Devon, PL6 8DH, United Kingdom

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Merseyside, Merseyside, CH63 4JY, United Kingdom

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Northwood, Middlesex, HA6 2RN, United Kingdom

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Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

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Taunton, Somerset, TA1 5DA, United Kingdom

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Cottingham, HU16 5JQ, United Kingdom

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Sheffield, S10 2SJ, United Kingdom

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Related Links

• Click here to find results for studies related to Bayer products.
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

MeSH Terms

Conditions

Breast Neoplasms

Interventions

radium Ra 223 dichloride; Sodium Chloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Due to the premature enrollment discontinuation, reduced sample size, and potentially curtailed active follow up, the planned number of SSE FS events was not achieved, limiting the assessment of the primary efficacy endpoint.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer AG

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: September 30, 2014
• First Posted: October 7, 2014
• Study Start: March 2, 2015
• Primary Completion: August 13, 2019
• Study Completion: August 13, 2019
• Last Updated: August 10, 2020
• Results First Posted: August 10, 2020

Record last verified: 2020-07

Locations

FR (2); IL (8); CA (4); DK (2); CH (1); ES (10); KR (6); US (11); CZ (2); PL (3); HK (1); SG (1); TW (1); NO (1); FI (2); AU (2); IE (2); GB (7); NL (2); DE (3)