stop_circleTerminated/Withdrawn

Breast Neoplasms

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

Trial purpose

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

Key Participants Requirements

Sex

Female

Age

18 - N/A
  • - 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.
  • - 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.

Trial summary

Enrollment Goal
99
Trial Dates
March 2015 - August 2019
Phase
Phase 2
Could I Receive a placebo
Yes
Products
Xofigo (Radium-223 dichloride, BAY88-8223)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Kfar Saba, 4428164, Israel
Withdrawn
Petach Tikva, 4941492, Israel
Completed
Zerifin, 7030000, Israel
Completed
Haifa, 3109601, Israel
Withdrawn
Rehovot, 7610001, Israel
Completed
Jerusalem, 9112001, Israel
Withdrawn
Beer Sheva, 8410101, Israel
Completed
Tel Aviv, 64239, Israel
Completed
Afula, 1834111, Israel
Withdrawn
Holon, 5822012, Israel
Completed
Ramat Gan, 5262000, Israel
Completed
Jerusalem, 9103102, Israel
Completed
Linz, 4020, Austria
Withdrawn
Leoben, 8700, Austria
Withdrawn
Linz, 4010, Austria
Completed
Innsbruck, 6020, Austria
Completed
Sheffield, S10 2SJ, United Kingdom
Completed
Nottingham, NG5 1PB, United Kingdom
Withdrawn
Philadelphia, 19104, United States
Withdrawn
Rochester, 55905, United States
Completed
Ann Arbor, 48109, United States
Withdrawn
Madrid, 28007, Spain
Completed
Madrid, 28033, Spain
Withdrawn
Palma de Mallorca, 07120, Spain
Terminated
Sevilla, 41071, Spain
Withdrawn
Madrid, 28046, Spain
Withdrawn
Pamplona, 31008, Spain
Completed
Barcelona, 08025, Spain
Completed
L'Hospitalet de Llobregat, 08907, Spain
Withdrawn
Padova, 35128, Italy
Withdrawn
Roma, 00189, Italy
Withdrawn
Palermo, 90146, Italy
Withdrawn
Bari, 70124, Italy
Withdrawn
Modena, 41124, Italy
Withdrawn
Reggio Emilia, 42123, Italy
Withdrawn
Genova, 16128, Italy
Withdrawn
Verona, 37024, Italy
Withdrawn
Milano, 20133, Italy
Completed
Cork, Ireland
Withdrawn
Forlì Cesena, 47014, Italy
Completed
Gdynia, 81-519, Poland
Withdrawn
Gdansk, 80-952, Poland
Withdrawn
Gliwice, 44-101, Poland
Withdrawn
Krakow, 31-051, Poland
Withdrawn
Lublin, 20-090, Poland
Completed
Bialystok, 15-027, Poland
Completed
Helsinki, 00290, Finland
Withdrawn
Vaasa, 65130, Finland
Completed
Tampere, FIN-33520, Finland
Withdrawn
Turku, FIN-20521, Finland
Withdrawn
Mainz, 55131, Germany
Withdrawn
Aachen, 52074, Germany
Terminated
Essen, 45147, Germany
Withdrawn
Köln, 50935, Germany
Completed
Málaga, 29010, Spain
Withdrawn
Barcelona, 08035, Spain
Terminated
Madrid, 28041, Spain
Withdrawn
Madrid, 28050, Spain
Completed
Madrid, 28040, Spain
Completed
Barcelona, 08036, Spain
Terminated
Zaragoza, 50009, Spain
Completed
Warszawa, 02-781, Poland
Withdrawn
Watertown, 57201, United States
Withdrawn
Spokane, 99208-1129, United States
Completed
Cedar Rapids, 52403, United States
Withdrawn
Long Beach, 90813, United States
Withdrawn
Detroit, 48202, United States
Withdrawn
Omaha, 68130, United States
Withdrawn
Ft. Lauderdale, 33316, United States
Withdrawn
Plantation, 33324, United States
Completed
Aurora, 80045, United States
Terminated
Pittsburgh, 15213-3180, United States
Completed
Pontiac, 48341, United States
Completed
Annapolis, 21401, United States
Completed
New Haven, 06520, United States
Withdrawn
Cleveland, 44195, United States
Completed
La Jolla, 92093, United States
Completed
St. Louis, 63110, United States
Withdrawn
Shatin, Hong Kong
Withdrawn
Hong Kong, Hong Kong
Completed
Hong kong, Hong Kong
Withdrawn
Hong Kong, Hong Kong
Terminated
København, 2100, Denmark
Terminated
Herlev, 2730, Denmark
Withdrawn
Odense C, 5000, Denmark
Completed
Seoul, 03080, Korea, Republic Of
Completed
Seoul, 05505, Korea, Republic Of
Withdrawn
Seoul, 06591, Korea, Republic Of
Completed
Seoul, 03722, Korea, Republic Of
Completed
Busan, 49241, Korea, Republic Of
Completed
Incheon, Korea, Republic Of
Withdrawn
Salamanca, 37007, Spain
Withdrawn
Monza-Brianza, 20900, Italy
Withdrawn
Roma, 00161, Italy
Withdrawn
Lugo, 27003, Spain
Withdrawn
Viganello, 6962, Switzerland
Completed
Tübingen, 72076, Germany
Completed
Bonn, 53105, Germany
Completed
A Coruña, 15009, Spain
Completed
London, N6A 4L6, Canada
Withdrawn
Montreal, H3T 1E2, Canada
Completed
Toronto, M5G 2M9, Canada
Withdrawn
Ottawa, K1H 8L6, Canada
Terminated
Winnipeg, R3E 0V9, Canada
Withdrawn
Göteborg, 413 45, Sweden
Withdrawn
Växjö, 35185, Sweden
Withdrawn
Bodø, 8092, Norway
Completed
Oslo, 0424, Norway
Withdrawn
Omaha, 68130, United States
Withdrawn
Newark, 07103, United States
Withdrawn
Cleveland, 44109-1998, United States
Completed
NIEUWEGEIN, 3435 CM, Netherlands
Withdrawn
HOOFDDORP, 2134 TM, Netherlands
Withdrawn
HEERLEN, 6401 CX, Netherlands
Withdrawn
DORDRECHT, 3318 AT, Netherlands
Withdrawn
Yuma, 85364, United States
Withdrawn
Milano, 20132, Italy
Withdrawn
MONTPELLIER CEDEX, 34298, France
Withdrawn
CLERMONT FERRAND CEDEX 1, 63011, France
Withdrawn
LA ROCHE SUR YON cedex, 85925, France
Withdrawn
DIJON, 21079, France
Completed
SAINT CLOUD, 92210, France
Withdrawn
GRENOBLE, 38043, France
Withdrawn
RENNES CEDEX, 35062, France
Withdrawn
VANDOEUVRE LES NANCY, 54000, France
Completed
Taunton, TA1 5DA, United Kingdom
Withdrawn
Bristol, BS2 8ED, United Kingdom
Withdrawn
Belfast, BT9 7AE, United Kingdom
Withdrawn
Guildford, GU27XX, United Kingdom
Terminated (Halted Prematurely)
Merseyside, CH63 4JY, United Kingdom
Completed
Northwood, HA6 2RN, United Kingdom
Withdrawn
Romford, RM7 0AG, United Kingdom
Withdrawn
Coventry, CV2 2DX, United Kingdom
Completed
Houston, 77230, United States
Withdrawn
Taoyuan, 33305, Taiwan
Withdrawn
Taipei, Taiwan
Withdrawn
Kaoshiung, 81346, Taiwan
Completed
Taipei, 11217, Taiwan
Withdrawn
Singapore, 217562, Singapore
Completed
Singapore, 119074, Singapore
Withdrawn
Singapore, 258499, Singapore
Completed
Cottingham, HU16 5JQ, United Kingdom
Withdrawn
Taiwan, Taiwan
Withdrawn
CAEN CEDEX 5, 14076, France
Withdrawn
Bologna, 40138, Italy
Terminated
Aarau, 5001, Switzerland
Completed
Dublin, 7, Ireland
Withdrawn
Galway, Ireland
Completed
Newmarket, L3Y 2P9, Canada
Withdrawn
Chomutov, 430 12, Czechia
Withdrawn
Olomouc, 775 20, Czechia
Completed
Ostrava, 708 52, Czechia
Completed
Praha 2, 12808, Czechia
Completed
PLYMOUTH, PL6 8DH, United Kingdom
Withdrawn
München, 81675, Germany
Withdrawn
Bismarck, 58501, United States
Withdrawn
NIJMEGEN, 6500 HB, Netherlands
Withdrawn
HAARLEM, 2035 RC, Netherlands
Withdrawn
Dublin 6, Ireland
Withdrawn
Beijing, 100730, China
Withdrawn
Guangzhou, 510060, China
Withdrawn
Guangzhou, 510080, China
Withdrawn
Shanghai, China
Withdrawn
Beijing, 100020, China
Withdrawn
Lake Success, 11042, United States
Withdrawn
Ashland, 41101, United States
Completed
Bakersfield, 93309, United States
Completed
Daegu, 42601, Korea, Republic Of
Withdrawn
Suwon-si, 442-723, Korea, Republic Of
Withdrawn
Sevilla, 41013, Spain
Completed
ZWOLLE, 8025 AB, Netherlands
Withdrawn
DEN HAAG, 2545 CH, Netherlands
Withdrawn
AMERSFOORT, 3818 TZ, Netherlands
Withdrawn
CHAMBERY CEDEX, 73011, France
Withdrawn
BRON, 69677, France
Completed
ANGERS CEDEX, 49055, France

Primary Outcome

  • 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
    date_rangeTime Frame:
    Up to approximately 51 months

Secondary Outcome

  • Overall survival
    Time from randomization to death from any cause
    date_rangeTime Frame:
    Up to approximately 51 months
  • Time to opiate use for cancer pain
    Interval from the date of randomization to the date of opiate use
    date_rangeTime Frame:
    Up to approximately 51 months
  • Time to pain progression
    Time from randomization to the first date a participants (only in participants with baseline WPS ≤8) experiences pain progression based on worst pain score (WPS) ranging from 0 to 10 and analgesic use. Pain progression is defined as an increase of 2 or more points in the “Worst pain in 24 hours” score from baseline observed at 2 consecutive evaluations ≥4 weeks apart or an increase in pain management (IPM) with respect to baseline, whichever occurs first
    date_rangeTime Frame:
    Up to approximately 51 months
  • Pain Improvement Rate
    The percentage of participants (baseline WPS>=2) with confirmed pain improvement at any time point. Confirmed pain improvement is defined as a 2 point decrease in worst pain score (WPS) from baseline over 2 consecutive assessment periods conducted at least 4 weeks apart
    date_rangeTime Frame:
    Up to approximately 51 months
  • Time to cytotoxic chemotherapy
    Time from the date of randomization to the date of the first cytotoxic chemotherapy
    date_rangeTime Frame:
    Up to approximately 51 months
  • Radiological progression-free survival (rPFS)
    Time from the date of randomization to the date of first radiological progression or death (if death occurs before progression)
    date_rangeTime Frame:
    Up to approximately 51 months
  • Number of participants with treatment-emergent adverse events
    Any event arising or worsening after the start of study drug administration until 30 days after the last study medication intake
    date_rangeTime Frame:
    Up to approximately 7 months
  • Number of participants with post-treatment adverse events including additional malignancies and chemotherapy related adverse events
    AEs related to the study drug, all occurrences of additional malignancies, febrile neutropenia and hemorrhage in subjects receiving chemotherapy, bone fractures and bone associated events (regardless of severity and relationship to study drug), and some symptoms needed for the characterization of an symptomatic skeletal event
    date_rangeTime Frame:
    From 30 days after the last dose of study treatment until the end of study, assessed up to approximately 44 months

Trial design

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
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
Double Blind
Assignment
Parallel Assignment
Trial Arms
2