Study of radium-223 dichloride versus placebo and hormonal treatment as background therapy in subjects with bone predominant HER2 negative hormone receptor positive metastatic breast cancer.
- Conditions
- HER2 negative hormone receptor positive metastatic breast cancer with bone metastases treated with standard of care hormonal treatment.MedDRA version: 20.1 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-002113-39-FI
- Lead Sponsor
- Bayer AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 227
1.Have provided written informed consent. Subjects must be able to understand and be willing to sign the written informed consent. A signed ICF must be appropriately obtained prior to the conduct of any study-specific procedure.
2.Documentation of histological or cytological confirmation of ER+ and HER2 negative adenocarcinoma of the breast must be available. HER2 status should be determined by an accredited/Ministry of Health approved laboratory by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH) or other validated in situ hybridization (ISH) assay for detection of HER2 gene expression.
3.Tumors (from either primary or metastatic sites) must be ER+ defined as =10% positive tumor nuclei in the analyzed sample. ER+/ progesterone receptor positive (PR+), ER+/ progesterone receptor negative (PR-) subjects are eligible whereas estrogen receptor negative (ER )/PR+ and ER-/PR- disease will not be eligible.
4.Women (=18 years of age) with metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy. Women of reproductive potential and their male partners must agree to use adequate contraception during treatment and for 6 months following the completion of treatment with radium 223 dichloride/placebo.
5.Documentation of menopausal status: post-menopausal or pre-menopausal subjects are eligible.
o Pre-menopausal subjects with or without ovarian radiation or concomitant treatment with an LH-RH agonist/antagonist must have a negative pregnancy test at screening and agree to use an adequate method of contraception as recommended by their treating physicians.
oPost-menopausal status is defined either by:
oage =55 years and one year or more of amenorrhea
oage <55 years and one year or more of amenorrhea with a plasma/serum estradiol assay within local laboratory postmenopausal range, performed within 7 days of randomization
obilateral ovariectomy
6.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.
7.Measurable or non-measurable disease (but radiologically evaluable) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. All disease burden must be assessed at baseline by CT or MRI of chest, pelvis, and abdomen and any additional fields as needed.
8.Subjects must have received at least one line of hormonal therapy in the metastatic setting.
9.Subjects who are eligible for further standard of care endocrine treatment with any of the following administered as in second line or greater of hormone therapy in metastatic setting:
oSERMs such as tamoxifen and toremifene
oNSAIs such as anastrozole and letrozole
oSteroidal AIs such as exemestane
oER down-regulators such as fulvestrant
10.Subjects must have experienced no more than 2 SREs prior to study entry defined as: Need for EBRT to bone, pathological bone fracture (excluding major trauma), spinal cord compression, and/
1. HER2-positive breast cancer (IHC=3+, positive FISH/CISH/other ISH validated assay); equivocal or unknown HER2 status
Note: Subjects with 3+ by IHC cannot be chosen regardless of their FISH/CISH/other ISH validated assay status and those with positive FISH/CISH/other ISH validated assay cannot be chosen either, regardless of the IHC findings. Subjects with 2+ by IHC will not be eligible if no negative FISH/CISH/other ISH validated assay for detection of HER2 gene expression is available.
2. Subjects considered by the treating physician to be appropriate candidates for treatment with everolimus as current treatment for their metastatic breast cancer.
3. Subjects with inflammatory breast cancer
5. 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/neoadjuvant disease is acceptable.
6. Subjects with any previous untreated or concurrent cancer that is distinct in primary site or histology from the cancer under study, except treated basal cell carcinoma or superficial bladder tumor (Ta and Tis, American Joint Committee on Cancer, 7th edition). Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before enrollment are allowed. All cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of informed consent form).
7. 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 is otherwise not required.
8. Imminent or established untreated spinal cord compression based on clinical findings and/or MRI. Following treatment of spinal cord compression, the subject may be eligible if all other eligibility criteria are fulfilled.
9. Prior treatment with radium-223 dichloride
10. Prior hemibody external radiotherapy. Subjects who received other types of prior external radiotherapy are allowed provided that bone marrow function is assessed and meets the protocol requirements for hemoglobin, absolute neutrophil count, and platelets.
11. Prior systemic radiotherapy with strontium-89, samarium-153, rhenium-186, or rhenium-188
12. ECOG Performance Status =2
13. Blood transfusions, platelet transfusions or use of erythropoietin within 4 weeks prior to randomization.
14. Use of biologic response modifiers, such as granulocyte macrophage-colony
stimulating factor or granulocyte-colony stimulating factor, within 4 weeks prior to randomization.
15. Treatment with an investigational drug or with any anti cancer treatments not permitted by the protocol, within 4 weeks prior to randomization
16. Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed Paget's disease of bone)
17. Any other serious illness or medical condition such as, but not limited to:
o Any uncontrolled infection
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy and safety of radium-223 dichloride in subjects with HER2 negative, hormone receptor positive breast cancer with bone metastases treated with hormonal treatment background therapy.;Secondary Objective: Not applicable. ;Primary end point(s): • Symptomatic skeletal event free survival(SSE-FS);<br> Timepoint(s) of evaluation of this end point: The time from randomization to the occurrence of one of the following:<br> (1) An on-study SSE, which is defined as:<br> a. the use of EBRT to relieve skeletal symptoms<br> b. the occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral)<br> c. the occurrence of spinal cord compression<br> d. a tumor related orthopedic surgical intervention.<br> (2) Death from any cause<br>
- Secondary Outcome Measures
Name Time Method