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
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| ClinicalTrials.gov Identifier: NCT02258464 |
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Recruitment Status :
Terminated
(Due to lower than expected recruitment since the start of study)
First Posted : October 7, 2014
Results First Posted : August 10, 2020
Last Update Posted : August 10, 2020
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Sponsor:
Bayer
Information provided by (Responsible Party):
Bayer
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Neoplasms | Drug: Radium-223 dichloride (Xofigo, BAY88-8223) Drug: Placebo (saline) Other: Background hormonal therapy | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 99 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | March 2, 2015 |
| Actual Primary Completion Date : | August 13, 2019 |
| Actual Study Completion Date : | August 13, 2019 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
Drug Information
available for:
Radium Ra 223 dichloride
| Arm | Intervention/treatment |
|---|---|
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Experimental: Radium 223 dichloride
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
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Drug: Radium-223 dichloride (Xofigo, BAY88-8223)
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) Other: Background hormonal therapy Prescribed by PI and was provided as long as patient can tolerate treatment. It must be prescribed as per local label in country participating. |
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Placebo Comparator: Placebo
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
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Drug: Placebo (saline)
Up to 6 cycles of saline injection Other: Background hormonal therapy Prescribed by PI and was provided as long as patient can tolerate treatment. It must be prescribed as per local label in country participating. |
Primary Outcome Measures :
- Symptomatic Skeletal Event Free Survival (SSE-FS) [ Time Frame: Up to approximately 51 months ]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
Secondary Outcome Measures :
- Overall Survival [ Time Frame: Up to approximately 51 months ]Time from randomization to death from any cause
- Time to Opiate Use for Cancer Pain [ Time Frame: Up to approximately 51 months ]Interval from the date of randomization to the date of opiate use
- Time to Pain Progression [ Time Frame: Up to approximately 51 months ]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
- Pain Improvement Rate [ Time Frame: Up to approximately 51 months ]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
- Time to Cytotoxic Chemotherapy [ Time Frame: Up to approximately 51 months ]Time from the date of randomization to the date of the first cytotoxic chemotherapy
- Radiological Progression-free Survival (rPFS) [ Time Frame: Up to approximately 51 months ]Time from the date of randomization to the date of first radiological progression or death (if death occurs before progression)
- Number of Participants With Treatment-emergent Adverse Events [ Time Frame: Up to approximately 7 months ]Any event arising or worsening after the start of study drug administration until 30 days after the last study medication intake
- Number of Participants With Post-treatment Adverse Events Including Additional Malignancies and Chemotherapy Related Adverse Events [ Time Frame: From 30 days after the last dose of study treatment until the end of study, assessed up to approximately 44 months ]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
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02258464
Locations
Show 71 study locations
Sponsors and Collaborators
Bayer
Investigators
| Study Director: | Bayer Study Director | Bayer |
Study Documents (Full-Text)
Documents provided by Bayer:
Documents provided by Bayer:
Statistical Analysis Plan [PDF] August 12, 2019
Study Protocol [PDF] April 3, 2018
Additional Information:
| Responsible Party: | Bayer |
| ClinicalTrials.gov Identifier: | NCT02258464 |
| Other Study ID Numbers: |
16298 2014-002113-39 ( EudraCT Number ) |
| First Posted: | October 7, 2014 Key Record Dates |
| Results First Posted: | August 10, 2020 |
| Last Update Posted: | August 10, 2020 |
| Last Verified: | July 2020 |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Bayer:
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Breast Cancer |
Additional relevant MeSH terms:
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases |
Skin Diseases Radium Ra 223 dichloride Antineoplastic Agents |