ISRCTN38635575已完成2 期
A proof of concept phase II study of Buparlisib in HER2 positive breast cancer with brain metastasis following HER2 directed monoclonal antibody therapy
niversity of Liverpool0 个研究点目标入组 24 人开始时间: 2017年1月31日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- All
入选标准
- •1. Female 16 years or above
- •2. Histologically confirmed HER2-positive breast cancer (immunohistochemistry 3+ or fluorescence in situ hybridization with an amplification ratio =2.0)
- •3. Newly diagnosed brain metastasis
- •4. At least one brain metastasis measuring =2.5cm (to minimise partial volume effects in PET imaging and quantification)
- •5. Previous treatment with Trastuzumab with or without Pertuzumab either in the adjuvant or metastatic setting
- •6. Discussed with neuro-oncology MDT and considered a candidate for macroscopic resection
- •7. ECOG performance status 0 to 2
- •8. Patient has adequate bone marrow and organ function as defined by the following laboratory values:
- •8.1. Absolute Neutrophil Count (ANC) > 1.0 x 109/L
- •8.2. Platelets (plt) >100 x 109/L
- •8.3. Haemoglobin (Hgb) = 9 g/dl
- •8.4. INR = 1.5
- •8.5. Potassium, calcium (corrected for serum albumin) and magnesium within normal limits
- •8.6. Serum creatinine = 1.5 x ULN
- •8.7. Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) within normal range (or < 3.0 x ULN if liver metastases are present)
- •8.8. Total serum bilirubin within normal range (or = 1.5 x ULN if liver metastases are present; or total bilirubin = 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert’s Syndrome, which is defined as presence of several episodes of unconjugated hyperbilirubinemia with normal results from Cells Blood Count (CBC), including normal reticulocyte count and blood smear, normal liver function test results, and absence of other contributing disease processes at the time of diagnosis
- •8.9. Alkaline phosphatase = 5 x upper limit of normal, unless bone metastases in the absence of liver disease
- •8.10. Fasting plasma glucose = 120 mg/dL or 6.7 mmol/L
- •8.11. HbA1c = 8 % (= 64mmol/mol)
- •9. Left ventricular Ejection Fraction (LVEF) > 50 % as determined echocardiogram
- •10. Life expectancy > 3 months
- •11. Ability to swallow and retain oral medication
- •12. Written informed consent, able to comply with treatment and follow up
排除标准
- •1. Prior treatment with Lapatinib or other HER2-directed tyrosine kinase inhibitor (given such patients will have already received some form of local therapy)
- •2. Cystic brain metastasis with minimal solid component (defined on MRI)
- •3. Prior treatment with either a P13K or AKT inhibitor
- •4. Receiving treatment with other antineoplastic agents (except for HER2-directed monoclonal antibody therapy)
- •5. Treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) = 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated before enrollment, may be continued.
- •5. Wide field radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia, bone marrow and organ functions)
- •6. Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects
- •7. Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders (defined according to DSM- IV). For patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug. For patients receiving psychotropic treatments at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
- •8. GAD-7 mood scale = 15
- •9. A score = 12 on the PHQ-9 questionnaire
- •10. Selection of response 1, 2 or 3” to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9)
- •11. CTCAE grade 3 anxiety
- •12. Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
- •12.1. Unstable angina pectoris within 6 months prior to study entry
- •12.2. Symptomatic pericarditis
- •12.3. Documented myocardial infarction within 6 months prior to study entry
- •12.4. History of documented congestive heart failure (New York Heart
- •Association functional classification III-IV)
- •12.5. Documented cardiomyopathy
- •13. QTcF > 480 msec on the screening ECG (using the QTcF formula)
- •14. Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to registration.
- •15. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of buparlisib
- •16. Prior malignancies (other than breast cancer) within the last 5 years, except for adequately treated in situ carcinoma of the cervix or basal cell/squamous cell carcinoma of the skin
- •17. Currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed
- •18. Current treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. Such agents must be discontinued for at least one week prior to starting treatment
- •19. History of non-compliance to medical regimen
- •20. Acute viral hepatitis or a history of chronic or act
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