Phase II Study of Abemaciclib plus Trastuzumab biosimilar(Herzuma®) ± Fulvestrant in Patients with HER2 Positive Metastatic Breast Cancer in Brain who Progressed after HER2 directed Chemotherapy
- Conditions
- Neoplasms
- Registration Number
- KCT0004338
- Lead Sponsor
- Korea University Anam Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- Female
- Target Recruitment
- 48
1. breast cancer patients with brain metastasis secondary to histologically or cytologically confirmed HER2+ amplified breast cancer by either immunohistochemistry(IHC) or in-situ hybridization(ISH).
a) To fulfill the requirement of HER2+ disease, the primary tumor or metastatic lesion of the breast cancer must demonstrate overexpression of HER2 by either IHC (3+) or gene amplification by positive in-situ hybridization(ISH) as defined in the relevant ASCO/CAP HER2 guidelines.
2. have measurable and/or non-measurable disease according to RECIST version 1.1.
3. patients must have received at least one regimen of systemic chemotherapy including HER2 directed agents for metastatic/recurrent disease.
4. patients with parenchymal brain metastasis must be stable for at least 2 weeks following whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS)
a) Patients are not required to have received prior local therapy for study participation.
5. patients have =1 new or not previously irradiated measurable metastatic brain lesion =10 mm in the longest diameter (LD) and =5 mm in the perpendicular plane or a progressive previously irradiated metastatic brain lesion on radiographic imaging by gadolinium-enhanced magnetic resonance imaging (Gd-MRI).
6. if receiving concomitant corticosteroids, must be on a stable or decreasing dose for at least 7 days prior to the baseline Gd-MRI.
7. have a performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) scale (appendix 1).
8. have a life expectancy =12 weeks.
9. patient is an adult, female = 19 years old at the time of informed consent.
10. Have previously received:
a) prior at least one line of HER2 directed therapy including trastuzumab for metastatic disease is mandatory. prior HER2-directed therapies could be in combination with chemotherapy or endocrine therapy or as single agent.
b) exposure to dual HER2 blockade (for example, combination trastuzumab and pertuzuma) is considered as 1 prior HER2-directed therapy.
c) prior trastuzumab and/or pertuzumab and/or lapatinib are allowed in any disease setting.
d) patients may have received previous any endocrine therapy with fulvestrant.
11. have discontinued all previous therapies for cancer (including cytotoxic chemotherapy, targeted therapy [including, but not limited to, everolimus], radiotherapy, immunotherapy, and investigational therapy) for at least 14 days prior to receiving abemaciclib and recovered from the acute effects of therapy (treatment-related toxicity resolved to baseline) except for residual alopecia or peripheral neuropathy.
12. have adequate organ function
a) bone marrow: a) ANC = 1.5 x 109/L; b) Platelets = 100 x 109/L; c) Hemoglobin = 8.0 g/dL
b) hepatic: total bilirubin = 1.5x upper normal limit(ULN) except in cases of known Gilbert’s syndrome where =2.0 times ULN is allowed) and alanine aminotransferase(ALT) and aspartate aminotransferase(AST) = 3 x ULN. If, liver metastases are present, AST and ALT = 5 x ULN are acceptable.
c) renal: creatinine = 1.5x ULN or CCr > 60 ml/min for patients with abnormal serum Cr level function.
13. must have left ventricular ejection fraction (LVEF) of 50% or higher at baseline (determined by echocardiography or multiple-gated acquisition scanning).
14.have postmenopausal status due to either surgical/natural menopause or induced by ovarian suppression
15. are reliable and willing to make themselves available for the duration of the study and are willing to foll
1. require immediate local therapy, including but not limited to WBRT, SRS, or surgical resection, for treatment of brain metastases.
2. are taking concurrent enzyme-inducing antiepileptic drugs (EIAED).
3. have evidence of significant (ie, symptomatic) intracranial hemorrhage.
4. have experienced >2 seizures within 4 weeks prior to study entry.
5. is pregnant or lactating, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
6. has received previous treatment with abemaciclib
a) patients may have received prior palbociclib or ribociclib, but only patients without progression of CNS on palbociclib or ribociclib will be allowed.
7. have known contraindication to Gd-MRI.
8. have a personal history within the last 12 months of any ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation) or sudden cardiac arrest
9. have a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea.
10. have a history of any other cancer (except non-melanoma skin cancer, carcinoma in-situ of the cervix, thyroid cancer with no lymph node metastasis), unless in complete remission with no therapy for a minimum of 3 years.
11. have an active systemic fungal and/or known viral infection (for example, human immunodeficiency virus antibodies or hepatitis C antibodies). Patients have hepatitis B surface antigen are eligible if they are on pre-emptive antiviral treatment. Screening is not required for enrollment.
12. have an acute bacterial infection requiring intravenous (IV) antibiotics
13. are currently enrolled in a clinical trial involving investigational product (IP) or non-approved use of a drug or device (other than the IP/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
14. have received any recent (within 28 days prior to randomization) live virus vaccination
15. history of interstitial lung disease (ILD) or severe dyspnea at rest or requiring oxygen therapy
16. hypersensitivity to trastuzumab, murine proteins, fulvestrant, or to any of the excipients.
17. History of bleeding diathesis (i.e. disseminated intravascular coagulation, clotting factor deficiency) or long-term anticoagulant therapy (although patients treated with anti-platelet therapy and low dose warfarin or other anticoagulant agents such as acenocoumarol are eligible providing they have an international normalised ratio [INR] of =1.6).
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective intracranial(IC) response rate defined by Response Assessment in Neuro-Oncology brain metastases(BM) response criteria
- Secondary Outcome Measures
Name Time Method progression-free survival;overall survival