Trial Condition(s):

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

Bayer Identifier:

16298

ClinicalTrials.gov Identifier:

NCT02258464

EudraCT Number:

2014-002113-39

Terminated/Withdrawn

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

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.

Trial Summary

Enrollment Goal

Trial Dates

March2015

August2019

Phase

Could I receive a placebo?

Yes

Products

Xofigo (Radium-223 dichloride, BAY88-8223)

Accepts Healthy Volunteers

Where to Participate

Locations

Status

Locations	Status
Locations Investigative Site Kfar Saba, Israel, 4428164	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Zerifin, Israel, 7030000	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Haifa, Israel, 3109601	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Jerusalem, Israel, 9112001	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Tel Aviv, Israel, 64239	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Afula, Israel, 1834111	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Ramat Gan, Israel, 5262000	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Jerusalem, Israel, 9103102	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Linz, Austria, 4020	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Innsbruck, Austria, 6020	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Sheffield, United Kingdom, S10 2SJ	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Nottingham, United Kingdom, NG5 1PB	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Ann Arbor, United States, 48109	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Madrid, Spain, 28033	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Sevilla, Spain, 41071	Status Terminated	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Barcelona, Spain, 08025	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site L'Hospitalet de Llobregat, Spain, 08907	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Cork, Ireland	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Gdynia, Poland, 81-519	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Bialystok, Poland, 15-027	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Helsinki, Finland, 00290	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Tampere, Finland, FIN-33520	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Essen, Germany, 45147	Status Terminated	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Málaga, Spain, 29010	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Madrid, Spain, 28041	Status Terminated	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Madrid, Spain, 28040	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Barcelona, Spain, 08036	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Zaragoza, Spain, 50009	Status Terminated	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Warszawa, Poland, 02-781	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Cedar Rapids, United States, 52403	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Aurora, United States, 80045	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Pittsburgh, United States, 15213-3180	Status Terminated	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Pontiac, United States, 48341	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Annapolis, United States, 21401	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site New Haven, United States, 06520	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site La Jolla, United States, 92093	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site St. Louis, United States, 63110	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Hong kong, Hong Kong, China	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site København, Denmark, 2100	Status Terminated	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Herlev, Denmark, 2730	Status Terminated	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Seoul, South Korea, 03080	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Seoul, South Korea, 05505	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Seoul, South Korea, 03722	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Busan, South Korea, 49241	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Incheon, South Korea	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Tübingen, Germany, 72076	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Bonn, Germany, 53105	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site A Coruña, Spain, 15009	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site London, Canada, N6A 4L6	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Toronto, Canada, M5G 2M9	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Winnipeg, Canada, R3E 0V9	Status Terminated	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Oslo, Norway, 0424	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site NIEUWEGEIN, Netherlands, 3435 CM	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site SAINT CLOUD, France, 92210	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Taunton, United Kingdom, TA1 5DA	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Northwood, United Kingdom, HA6 2RN	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Houston, United States, 77230	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Taipei, Taiwan, China, 11217	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Singapore, Singapore, 119074	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Cottingham, United Kingdom, HU16 5JQ	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Aarau, Switzerland, 5001	Status Terminated	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Dublin, Ireland, 7	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Newmarket, Canada, L3Y 2P9	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Ostrava, Czech Republic, 708 52	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Praha 2, Czech Republic, 12808	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site PLYMOUTH, United Kingdom, PL6 8DH	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Bakersfield, United States, 93309	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site Daegu, South Korea, 42601	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site ZWOLLE, Netherlands, 8025 AB	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937
Locations Investigative Site ANGERS CEDEX, France, 49055	Status Completed	Contact Us: E-mail: [email protected] Phone: (+) 1-888-8422937

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:

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
Timeframe: Up to approximately 51 months

Secondary Outcome

Overall survival
Time from randomization to death from any cause
Timeframe: Up to approximately 51 months

Time to opiate use for cancer pain
Interval from the date of randomization to the date of opiate use
Timeframe: 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
Timeframe: 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
Timeframe: Up to approximately 51 months

Time to cytotoxic chemotherapy
Time from the date of randomization to the date of the first cytotoxic chemotherapy
Timeframe: 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)
Timeframe: 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
Timeframe: 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
Timeframe: From 30 days after the last dose of study treatment until the end of study, assessed up to approximately 44 months

Breast Neoplasms

Bayer Identifier:

ClinicalTrials.gov Identifier:

EudraCT Number:

Trial Purpose

Key Participation Requirements

sex

age

18 Years

No Limit

Inclusion Criteria

Exclusion Criteria

Inclusion Criteria

Exclusion Criteria

Trial Summary

Enrollment Goal

Trial Dates

Phase

Could I receive a placebo?

Products

Accepts Healthy Volunteers

Where to Participate

Trial Design

Primary Outcome

Secondary Outcome

Additional Information