Clinical trial NCT02258451: Study of Radium-223 Dichloride in Combination With Exemestane and Everolimus Versus Placebo in Combination With Exemestane and Everolimus in Subjects With Bone Predominant HER2 Negative Hormone Receptor Positive Metastatic Breast Cancer
Official title: A Phase II Randomized, Double-blind, Placebo-controlled Trial of Radium-223 Dichloride in Combination With Exemestane and Everolimus Versus Placebo in Combination With Exemestane and Everolimus When Administered to Metastatic HER2 Negative Hormone Receptor Positive Breast Cancer Subjects With Bone Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Neoplasms
Keywords: Breast Cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2014-10-07
Enrollment: 283
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 is to assess efficacy and safety of radium 223 dichloride in subjects with human epidermal growth factor receptor 2 (HER2) negative hormone receptor positive breast cancer with bone metastases treated with exemestane and everolimus

After implementation of CSP Amendment 10, only a limited number of subjects will remain in this study, in order to reduce the burden to study subjects, collection of data will be reduced and will focus mainly on acute safety, SSE, and OS. Once subjects are rolled over, the long-term safety will be collected and assessed entirely in the separate extended safety follow-up study.


Eligibility criteria: Inclusion Criteria:

* Women (≥18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy.
* Documentation of histological or cytological confirmation of estrogen receptor positive (ER+) and HER2 negative adenocarcinoma of the breast must be available.
* Documentation of menopausal status: postmenopausal subjects or pre-menopausal subjects with ovarian radiation or concomitant therapy with a luteinizing hormone-releasing hormone (LH-RH) agonist/antagonist are eligible.
* Subjects with bone dominant disease with at least 2 skeletal metastases identified at baseline by bone scintigraphy and confirmed by computed tomography (CT)/magnetic resonance imaging (MRI).
* Subjects must have received at least one line of hormonal therapy in the metastatic setting.
* Subjects who are eligible as per the Investigator's assessment and according to the local label for treatment with exemestane and everolimus as a second line or greater of hormone therapy in a metastatic setting.
* Subjects must have experienced recurrent/progressive disease following treatment with a non-steroidal aromatase inhibitor (letrozole or anastrozole) in an adjuvant or metastatic setting
* Subjects must have experienced no more than two skeletal-related events (SREs) prior to study entry defined as: need for external beam radiotherapy (EBRT) to bone pain, 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 bisphosphonates or denosumab for at least 1 month before start of study treatment.
* Adequate hematological, liver and kidney function.

Exclusion Criteria:

* Subjects with Inflammatory breast cancer.
* Patients with immediately life-threatening visceral disease for whom chemotherapy is preferred treatment option.
* 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 provided it was administered at least 1 year prior to study entry.
* Subjects who received prior treatment or are already receiving everolimus treatment prior to study entry are not eligible.
* 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.

Primary outcomes:
measure: Symptomatic Skeletal Event-free Survival (SSE-FS)
timeFrame: Up to 55 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 55 months
measure: Time to Opiate Use for Cancer Pain
timeFrame: Up to 55 months
measure: Time to Pain Progression
timeFrame: Up to 55 months
measure: Time to Cytotoxic Chemotherapy
timeFrame: Up to 55 months
measure: Radiological Progression-free Survival (rPFS)
timeFrame: Up to 55 months
measure: Percentage of Participants With Pain Improvement
timeFrame: Up to 55 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dosing up to 30 days after the last administration of study treatments, up to 72.6 months
measure: Number of Participants With Post-treatment Chemotherapy Related Adverse Events
timeFrame: From post-treatment till end of study, up to 45.8 months
measure: Number of Participants With Hematological Toxicities: Worst Grade Under Treatment
timeFrame: From first dosing up to 30 days after the last administration of study treatments, up to 72.6 months
measure: Number of Participants With New Primary Malignancies
timeFrame: From first dosing till end of study, up to 72.6 months
Other outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) (From First Dosing Till Primary Analysis)
timeFrame: From first dosing till primary analysis cutoff date, up to 55 months
measure: Number of Participants With Post-treatment Chemotherapy Related Adverse Events (From First Dosing Till Primary Analysis)
timeFrame: From post-treatment till primary analysis cutoff date, up to 55 months
measure: Number of Participants With Hematological Toxicities: Worst Grade Under Treatment (From First Dosing Till Primary Analysis)
timeFrame: From first dosing till primary analysis cutoff date, up to 55 months
measure: Number of Participants With New Primary Malignancies During Study Treatment Till Primary Analysis
timeFrame: From first dosing till primary analysis cutoff date, up to 55 months
Locations:
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Hollywood
country: United States
state: Florida
city: Ashland
country: United States
state: Kentucky
city: Rockville
country: United States
state: Maryland
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Pontiac
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Newark
country: United States
state: New Jersey
city: Jamaica
country: United States
state: New York
city: Watertown
country: United States
state: South Dakota
city: Spokane
country: United States
state: Washington
city: Innsbruck
country: Austria
city: Bruxelles
country: Belgium
city: Edegem
country: Belgium
city: Kortrijk
country: Belgium
city: Leuven
country: Belgium
city: Angers Cedex
country: France
city: Nantes
country: France
city: NIMES Cedex 9
country: France
city: Saint-Cloud
country: France
city: Tours
country: France
city: Herne
country: Germany
state: Nordrhein-Westfalen
city: Chai Wan
country: Hong Kong
city: Hong Kong
country: Hong Kong
city: Kowloon
country: Hong Kong
city: Afula
country: Israel
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Holon
country: Israel
city: Jerusalem
country: Israel
city: Jerusalem
country: Israel
city: Ramat Gan
country: Israel
city: Tel Aviv
country: Israel
city: Zrifin
country: Israel
city: Bologna
country: Italy
state: Emilia-Romagna
city: Forlì Cesena
country: Italy
state: Emilia-Romagna
city: Modena
country: Italy
state: Emilia-Romagna
city: Roma
country: Italy
state: Lazio
city: Roma
country: Italy
state: Lazio
city: Genova
country: Italy
state: Liguria
city: Cremona
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Bari
country: Italy
state: Puglia
city: Pisa
country: Italy
state: Toscana
city: Nagoya
country: Japan
state: Aichi
city: Sapporo
country: Japan
state: Hokkaido
city: Osakasayama
country: Japan
state: Osaka
city: Hidaka
country: Japan
state: Saitama
city: Kita-Adachigun
country: Japan
state: Saitama
city: Koto-ku
country: Japan
state: Tokyo
city: Kagoshima
country: Japan
city: Osaka
country: Japan
city: Suwon-si
country: Korea, Republic of
state: Gyeonggido
city: Seoul
country: Korea, Republic of
state: Seoul Teugbyeolsi
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: Oslo
country: Norway
city: Bialystok
country: Poland
city: Gdansk
country: Poland
city: Gdynia
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Palma de Mallorca
country: Spain
state: Illes Baleares
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Pamplona
country: Spain
city: Sevilla
country: Spain
city: Sevilla
country: Spain
city: Aarau
country: Switzerland
state: Aargau
city: Kaohsiung City
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei City
country: Taiwan
city: Taipei
country: Taiwan
city: Truro
country: United Kingdom
state: Cornwall
city: Plymouth
country: United Kingdom
state: Devon
city: Nottingham
country: United Kingdom
state: Nottinghamshire
city: Taunton
country: United Kingdom
state: Somerset
city: Bristol
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: