Clinical trial NCT02258464: 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
Official title: A Phase II Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride Versus Placebo When Administered to Metastatic HER2 Negative Hormone Receptor Positive Breast Cancer Subjects With Bone Metastases Treated With Hormonal Treatment Background Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Neoplasms
Keywords: Breast Cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2014-10-07
Enrollment: 99
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Symptomatic Skeletal Event Free Survival (SSE-FS)
timeFrame: Up to approximately 51 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to approximately 51 months
measure: Time to Opiate Use for Cancer Pain
timeFrame: Up to approximately 51 months
measure: Time to Pain Progression
timeFrame: Up to approximately 51 months
measure: Pain Improvement Rate
timeFrame: Up to approximately 51 months
measure: Time to Cytotoxic Chemotherapy
timeFrame: Up to approximately 51 months
measure: Radiological Progression-free Survival (rPFS)
timeFrame: Up to approximately 51 months
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: Up to approximately 7 months
measure: Number of Participants With Post-treatment Adverse Events Including Additional Malignancies and Chemotherapy Related Adverse Events
timeFrame: From 30 days after the last dose of study treatment until the end of study, assessed up to approximately 44 months
Other outcomes:
Locations:
city: Bakersfield
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: New Haven
country: United States
state: Connecticut
city: Cedar Rapids
country: United States
state: Iowa
city: Annapolis
country: United States
state: Maryland
city: Ann Arbor
country: United States
state: Michigan
city: Pontiac
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Pittsburgh
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Linz
country: Austria
state: Oberösterreich
city: Innsbruck
country: Austria
city: Winnipeg
country: Canada
state: Manitoba
city: London
country: Canada
state: Ontario
city: Newmarket
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Ostrava
country: Czechia
city: Praha 2
country: Czechia
city: Copenhagen
country: Denmark
city: Herlev
country: Denmark
city: Helsinki
country: Finland
city: Tampere
country: Finland
city: Angers Cedex
country: France
city: Saint Cloud
country: France
city: Tübingen
country: Germany
state: Baden-Württemberg
city: Bonn
country: Germany
state: Nordrhein-Westfalen
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Kowloon
country: Hong Kong
city: Cork
country: Ireland
city: Dublin
country: Ireland
city: Afula
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Ramat Gan
country: Israel
city: Tel Aviv
country: Israel
city: Zerifin
country: Israel
city: Busan
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Nieuwegein
country: Netherlands
city: Zwolle
country: Netherlands
city: Oslo
country: Norway
city: Bialystok
country: Poland
city: Gdynia
country: Poland
city: Warszawa
country: Poland
city: Singapore
country: Singapore
city: L'Hospitalet de Llobregat
country: Spain
state: Barcelona
city: A Coruña
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: Sevilla
country: Spain
city: Zaragoza
country: Spain
city: Aarau
country: Switzerland
state: Aargau
city: Taipei
country: Taiwan
city: Plymouth
country: United Kingdom
state: Devon
city: Northwood
country: United Kingdom
state: Middlesex
city: Nottingham
country: United Kingdom
state: Nottinghamshire
city: Taunton
country: United Kingdom
state: Somerset
city: Cottingham
country: United Kingdom
city: Merseyside
country: United Kingdom
city: Sheffield
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: