EUCTR2009-016862-10-FR进行中（未招募）1 期
A Phase 1/2 Study of XL147 Administered in Combination with Trastuzumab or Paclitaxel andTrastuzumab in Subjects with Metastatic Breast Cancer who have Progressed on a Previous Trastuzumab-Based Regimen
Exelixis INC.0 个研究点目标入组 74 人开始时间: 2010年3月29日最近更新:
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 74
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- Female
入选标准
- •1. The subject has pathologically and radiologically confirmed metastatic HER2 positive breast cancer (Stage IV
- •disease). The following restrictions to prior anti-cancer therapy apply:
- •a. Subjects must have received and progressed on at least one prior trastuzumab-containing regimen for
- •metastatic disease, or have received trastuzumab as adjuvant treatment and progressed within 1 year of their last
- •dose of trastuzumab.
- •b. Subjects must have received at least one prior taxane-containing regimen as adjuvant treatment or for
- •metastatic disease (Arm 2).
- •c. Subjects must have received no more than five prior cytotoxic chemotherapeutic regimens for MBC (Phase 2).
- •Note: consecutive re-treatment with the same regimen does count as one regimen.
- •NOTE: Drugs used to control bone pain and/or osteoporosis (eg, bisphosphonates) are allowed if started at least 2
- •months prior to screening activities or may be initiated during the course of the study with the agreement of the
- •2. The subject has at least one lesion that is not within a previously radiated field and measurable on
- •computerized tomography (CT) or magnetic resonance imaging scan (MRI) per RECIST Version 1.1.
- •NOTE: Bone lesions are not considered measurable by definition. Primary breast lesions are not considered
- •measurable if assessed only by physical examination.
- •3. The subjects enrolled in Phase 2 of both treatment arms must be willing to undergo a biopsy of the primary
- •tumor or a tumor metastasis at baseline, if tumor tissue is amenable to biopsy. Fresh tissue from this biopsy
- •must be in the possession of the participating site/institution, and designated for shipment to the sponsor or a
- •laboratory designated by the sponsor.
- •4. The subject’s primary tumor and/or metastatic lesion must overexpress HER2. Acceptable methods of
- •measurement of HER2 overexpression/amplification include immunohistochemical (IHC) based assessments and
- •fluorescence in situ hybridization (FISH). Tumors tested by IHC must be 3+ positive. Tumors tested by FISH
- •must have a ratio of HER2:CEP17 > 2.0.
- •5. The subject is = 18 years old.
- •6. For subjects enrolled in Phase 2 of both treatment arms: at least fifteen (15) 4-10 micron tissue sections (=
- •15 unstained slides [20 preferable], without cover slips) from archival or fresh tissue, or a tissue block of the
- •subject’s tumor should be identified, in the possession of the participating site/institution, and designated for
- •shipment to the sponsor or a laboratory designated by the sponsor.
- •If, after the enrollment of the first 10 subjects in each arm, the incidence of molecular alterations directly
- •affecting the PI3K pathway in these 10 subjects in each arm is not between 40 and 60%, subject pre-selection
- •may be implemented and subsequent enrollment may be gated by alteration status to ensure that the frequency of
- •PI3K pathway alterations falls within the range of 40-60% for the study population in each arm.
- •7. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of = 2.
- •8. The subject has organ and marrow function as follows:
- •a. Absolute neutrophil count (ANC) = 1500/mm3.
- •b. Platelets = 100,000/mm3.
- •c. Hemoglobin = 9 g/dL.
- •d. Bilirubin = 1.5 × the upper limit of normal (ULN).
- •e. Serum creatinine = 1.5 × the ULN or calculated creatinine clearance = 60 mL/min.
- •f. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × the ULN if no liver
- •involvement, or = 5 × the ULN with liver involvement.
- •9. The subject is capable o
排除标准
- •1. The subject has previously been treated with a selective inhibitor of PI3K and / or AKT.
- •2. The following restrictions on prior therapy apply:
- •a. Small molecule targeted (non-cytotoxic) inhibitors (including investigational kinase inhibitors) within 2
- •weeks or 5 half-lives of the compound or active metabolites, whichever is longer, before the first dose of study
- •b.Radiation therapy within 2 weeks before the first dose of study treatment.
- •c. Hormonal therapy within 2 weeks before the first dose of study treatment.
- •d.Cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks, or nitrosoureas or
- •mitomycin C within 6 weeks before the first dose of study treatment.
- •e. Biologic therapy (including antibodies {other than trastuzumab}, immune modulators, cytokines) within 4
- •weeks before the first dose of study treatment. Note: There is no washout period required for trastuzumab.
- •f. Any other type of investigational agent within 4 weeks
- •g. Major surgery, or not recovered from major surgery, within 4 weeks before the first dose of study treatment.
- •3. The subject has not recovered from toxicity due to prior therapy to Grade = 1 or to pre-therapy baseline. Grade 2 alopecia related to prior therapies will not affect the eligibility of the subject in Arm 1 and Arm 2. Grade 2 peripheral neuropathy will not affect the eligibility in Arm 1 but is an exclusion criterion for Arm 2.
- •4. The subject has untreated, symptomatic, or progressive brain metastases. Subjects must have no radiographic or other signs of progression in the brain for =1 month after completion of local therapy. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for =4 weeks prior to first study treatment.
- •5. The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results at screening that are = 1.3 x the laboratory ULN.
- •6. The subject has a diagnosis of uncontrolled diabetes mellitus (glycosylated hemoglobin A1C = 8%) or has a fasting plasma glucose > 160 mg/dL
- •7. The subject has uncontrolled significant intercurrent illness including, but not limited to, ongoing or active infection requiring systemic treatment, or stroke within 3 months of screening.
- •8. The subject has uncontrolled hypertension (persistent values of = 150 mm Hg systolic or 100 mm Hg diastolic despite anti hypertensive therapy); or significant cardiovascular disease, eg, = New York Heart Association (NYHA) Class III congestive heart failure (CHF); or uncontrolled clinically significant atrial or ventricular cardiac arrhythmias; or any of the following in the past 6 months:
- •a. myocardial infarction
- •b. evidence of transmural infarction on ECG
- •c. unstable angina
- •d. coronary angioplasty
- •9. The subject has left ventricular ejection fraction (LVEF) = 50% of the expected LVEF as documented by multiple-gated acquisition (MUGA) or echocardiogram (ECHO) performed within 28 days prior to the first dose of study drug.
- •10. The subject has a baseline corrected QT interval = 460 ms.
- •11. The subject is currently receiving anticoagulation with therapeutic doses of warfarin (low-dose warfarin = 1mg/day is permitted).
- •12. The subject is taking oral corticosteroids (equivalent to prednisone > 7.5 mg daily) chronically.
- •13. The subject is pregnant or breastfeeding.
- •14. The subject is known to be positive for the human immunodeficiency virus (HIV) (a test for HIV at scre
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