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.
- Conditions
- Metastatic HER2 negative hormone receptor positive breast cancer subjects with bone metastasesMedDRA version: 20.1Level: PTClassification code 10055113Term: Breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-002114-23-NL
- Lead Sponsor
- Bayer AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 283
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 trial-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), or 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+) and 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: postmenopausal subjects or pre-menopausal subjects with ovarian radiation or concomitant therapy with a luteinizing hormone-releasing hormone (LH-RH) agonist/antagonist are eligible.
• Pre-menopausal subjects with ovarian radiation or concomitant treatment with an LH-RH agonist/antagonist must have a plasma/serum estradiol assay within local laboratory postmenopausal range at screening, performed within 7 days prior to randomization.These subjects must also have a negative pregnancy test at screening and agree to use an adequate method of contraception as recommended by their treating physicians.
• Post-menopausal status is defined either by:
• age =55 years and one year or more of amenorrhea,
• age <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
• bilateral ovariectomy
6. 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). 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 within 3 weeks prior to randomization by CT or MRI of chest, pelvis, and abdomen and any additional fields as needed. A Tc99m bone scan should also be done within 3 weeks prior to randomization for all subjects. CT/MRI done as
part of the standard of practice within 3 weeks prior to randomization and standard-of-care Tc99m bone scans done within 3 weeks prior to randomization are acceptable.
F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scan, if performed as part of standard of care imaging, can be used as an adjunct to CT/MRI in line with RECIST 1.1 guidelines. If FDG PET/CT scan, the CT component of the scan can be used for tumor measurements only if the site can document that the CT is of identic
1. HER2-positive breast cancer (immunohistochemistry [IHC] =3+, positive FISH, or positive CISH); 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. Patients with immediately life-threatening visceral disease, for whom chemotherapy is the preferred treatment option
3. Lymphangitic carcinomatosis
4. Patients with ascites requiring paracentesis within 2 weeks prior to study entry (signature of informed consent) and during the screening period
5. Subjects with inflammatory breast cancer
6. 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.
7. 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 ICF)
8. 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.
9. 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.
10. Prior treatment with radium-223 dichloride.
11. 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 Hb, absolute neutrophil count, and platelets.
12. Prior systemic radiotherapy with strontium-89, samarium-153, rhenium-186, or rhenium-188.
13. ECOG PS =2.
14. Blood transfusions, platelet transfusions or use of erythropoietin within 4 weeks prior to randomization.
15. Use of biologic response modifiers, such as granulocyte macrophage colony-stimulating factor or granulocyte colony stimulating factor, within 4 weeks prior to randomization.
16. Treatment with an investigational drug or with any anti-cancer treatments not permitted by the protocol, within 4 weeks prior to randomization
17. Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed Paget's disease of bone)
18. Any other serious illness or medical condition such as, but not limited to:
• Any uncontrolled infection
• Cardiac failure New York Heart Association Class III or IV
• Crohn's disease or ulcerative colitis
• Bone marrow dysplasia
19. Previous assignment to treatment in this study
20. Breast-feeding women
21.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The objective of this study is to assess efficacy and safety of radium 223 dichloride in combination with exemestane and everolimus in subjects with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor positive breast cancer with bone metastases.;Secondary Objective: Not applicable.;Primary end point(s): Symptomatic skeletal event free survival(SSE-FS);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