A Phase 1b Study of Bcl-2 inhibition with ABT-199 in combination with Tamoxifen in Metastatic ER-Positive Breast Cancer

Melbourne Health0 个研究点目标入组 45 人开始时间: 2015年7月7日最近更新: 2021年1月5日

适应症

试验速览

阶段: 1 期
状态: 已完成
发起方: Melbourne Health
入组人数: 45

研究概览研究设计入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional
分配方式: Non-randomised trial
主要目的: Treatment

入排标准

年龄范围: 18 Years 至 o limit（—）
性别: All

入选标准

•1. Subjects greater than or equal to 18 years of age
•2. Signed informed consent
•3. Histological or cytological confirmation* of metastatic carcinoma of the breast with the following tumor molecular characteristics:
•a) ER positive (>1% positive stained carcinoma cells)
•b) Bcl-2 positive (defined as >10% cells with at least moderate cytoplasmic staining; intensity 2-3 on 0-3 scale)
•c) HER2 non-amplified
•*Biopsy of a metastatic site is strongly encouraged in the Dose Expansion Stage and will be essential in at least 10 patients with visceral metastases.
•4. A tumor paraffin tissue block or at least 15 unstained slides from the tumor tissue block from either the primary tumor or a metastatic site (in addition to the initial 6 slides sent for Pre-Screening) must be available for biomarker analyses.
•* In the event that this is not available, permission to be enrolled on the study must be obtained from the Principal Investigator
•5. For the dose expansion phase, subject must not have received more than 3 lines in total of chemotherapy and/or endocrine therapy in the metastatic setting.
•6. Subjects must not have received tamoxifen within the last 3 months.
•7. Subject must have evaluable or measurable disease (bone-only metastases are allowed).
•*For the Dose Expansion Stage, only bony lesions clearly measurable on CT or MRI will be allowed if bone is the only site of disease
•8. Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 1
•9. Subjects of childbearing potential (ie. Not postmenopausal for at least 2 years or surgically sterile) must have negative results for pregnancy test performed at screening with a serum sample obtained within 14 days prior to the first study drug administration.
•10.Subject must have adequate organ and marrow function as defined below:
•a) Hemoglobin >9 g/dL
•b) Absolute neutrophil count > 1.5 x 109/L
•c) Platelet count > 100 x 109/L
•d) ALT and AST less than or equal to 2.5 x upper limit of normal (ULN), or less than or equal to 5 x ULN if liver metastases are present
•e) Total serum bilirubin less than or equal to 1.5 x ULN. Subjects with Gilbert’s syndrome may have a bilirubin >1.5 x ULN, per discussion with the investigator.
•f) Serum creatinine less than or equal to 1.5 xULN
•11. Life expectancy > 6 months
•12. Subjects must be suitable for oral drug administration

排除标准

•1. Subjects who have previously been exposed to ABT-199
•2.Absolute contraindication to tamoxifen use (e.g. life-threatening thromboembolic complications)
•3.Subjects who are pregnant or lactating
•4.Subjects with uncontrolled CNS metastases. Subjects who have had previous treatment of brain metastases with surgery or radiotherapy may be eligible if:
•a) Treatment was administered > 4 weeks prior to study entry;
•b) Subject is asymptomatic from CNS metastases; and
•c) If subject is on steroid medication for the purpose of controlling CNS metastases, this must be stable (i.e. no change in dose for at least 2 weeks from the date of first dose of ABT-199).
•5.Any anti-cancer therapy received within 21 days of the first dose of study drug including chemotherapy, radiotherapy or other investigational therapy. Exceptions: a) Bisphosphonate therapy or denosumab is allowed for subjects with bone metastases. b) Radiotherapy with palliative intent to non-target sites is allowed.
•6.Subjects who are taking warfarin. The use of alternative anticoagulation therapy such as systemic low-molecular weight heparin should be discussed with the investigator.
•7.Subjects who have had major surgery within 21 days of the first dose of study drug.
•8.Subject has received the following agents within 7 days prior to the first dose of study drug:
•a) Steroid therapy for anti-neoplastic intent;
•b) CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin;
•c) Potent CYP3A inducers such as rifampicin, carbamazepine, phenytoin and St. John’s Wort.
•9.Subjects with active uncontrolled infection.
•10.Known history of human immunodeficiency virus (HIV) infection, chronic Hepatitis B or C.
•11.History of other malignancies within the past 5 years except for treated skin basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma less than or equal to 1.0 mm without ulceration, localised thyroid cancer, or cervical carcinoma in situ. Other malignancies considered to be at low risk of recurrence may also be included according to the discretion of the Chief Investigator.
•12.Other history of medical or psychiatric condition that may interfere with the subject’s participation in the study.
•13.Subjects with childbearing potential who refuse to use at least one of the following methods of contraception during and for a period of 30 days after study drug discontinuation:
•a) Total abstinence from sexual intercourse as the preferred lifestyle of the subject; periodic abstinence is not acceptable;
•b) Surgically sterile partner(s) e.g. vasectomy
•c) Intrauterine device (IUD) or Mirena
•d) Double-barrier method (contraceptive sponge, diaphragm or cervical cap with spermicidal jellies or cream AND a condom)
•14.Subjects on contraception that is estrogen or progestin based (Mirena accepted)
•15.Subjects who are on Hormone Replacement Therapy

研究者

发起方

Melbourne Health

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