jRCT2031230090招募中不适用
A Phase I Study of OTS167PO, a MELK inhibitor, to Evaluate Safety, Tolerability and Pharmacokinetics in Patients with Advanced Breast Cancer and Dose-Expansion Study in Patients with Triple Negative Breast Cancer. (OTS1070103)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 70
- 主要终点
- maximum tolerated dose (MTD)
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
- Single Arm Study
- 干预模型
- Single Assignment
- 主要目的
- Treatment Purpose
- 盲法
- Open(masking Not Used)
入排标准
- 年龄范围
- 18age old over 至 No limit（—）
- 性别
- Female
入选标准
- •Dose Escalation and Dose Expansion Cohorts
- •Female patients, >= 18 years of age at the time of obtaining informed consent.
- •Patients with a documented (histologically or cytologically proven) breast cancer that is locally advanced or metastatic.
- •Patients with a malignancy that is either relapsed/refractory to standard therapy or for which no standard therapy is available.
- •Patients with a malignancy that is currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
- •Patients with measurable or non measurable disease according to the Response Evaluation Criteria In Solid Tumor (RECIST, v1.1).
- •Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (see APPENDIX B: Performance Status Evaluation).
- •Life expectancy of greater than or equal to 3 months.
- •Resolution of all chemotherapy-related or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (less than or equal to Grade 2).
- •Patients who are either not of childbearing potential or who agree to use a medically effective method of contraception during the study and during 3 months after the last dose of study drug. (See Appendix H: Forms of contraception).
- •Patients with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol.
- •Dose expansion Cohort for TNBC
- •Patients with conditions as follows;
- •ER <10%, PR <10% by IHC assay, and HER2 negative based on ASCO CAP guideline
- •Patients with measurable disease according to the response evaluation criteria in TNBC (RECIST, v1.1)
- •Patients with measurable disease that can be easily accessed for biopsy.
- •Relapsed (recurrence or disease progression after achieving a documented clinical response to first- or second-line treatment) or refractory (disease progression while receiving first line or second line treatment). In the case of TNBC, prior initial therapy with at least one known active regimen for TNBC including, but not limited to, any combination of anthracyclines, taxanes, platinum agents, Ixabepilone, and/or cyclophosphamide is required.
排除标准
- •Dose Escalation and Expansion Cohorts
- •Women who are pregnant or lactating. Women of child-bearing potential (WOCBP) not using adequate birth control see Appendix H: Forms of contraception.
- •Patients with known central nervous system (CNS) or leptomeningeal metastases not controlled by prior surgery, radiotherapy or requiring corticosteroids to control symptoms, or patients with symptoms suggesting CNS involvement for which treatment is required.
- •Patients with primary brain tumors.
- •Patients with any hematologic malignancy. This includes leukemia (any form), lymphoma, and multiple myeloma.
- •Patients with any of the following hematologic abnormalities at baseline. (Patients may have received a red blood cell product transfusion prior to study, if clinically warranted.):
- •Absolute neutrophil count (ANC) < 1,500 per mm3
- •Platelet count < 100,000 per mm3
- •Hemoglobin < 8.0 gm/dL
- •Patients with any of the following serum chemistry abnormalities at baseline:
- •Total bilirubin >= 1.5 times the ULN for the institution value
- •AST or ALT >= 3 times the ULN for the institution value (>= 5 times if due to hepatic involvement by tumor)
- •Creatinine >= 1.5 times ULN for the institution value (or a calculated creatinine clearance < 60 mL/min/1.73 m2)
- •Patients with a significant active cardiovascular disease or condition, including:
- •Congestive heart failure (CHF)requiring therapy
- •Need for antiarrhythmic medical therapy for a ventricular arrhythmia
- •Severe conduction disturbance
- •Unstable angina pectoris requiring therapy
- •QTc interval > 450 msec (males) or > 470 msec (females)
- •QTc interval =< 300 msec
- •History of congenital long QT syndrome or congenital short QT syndrome
- •LVEF < 50% as measured by echocardiography or MUGA scan
- •Uncontrolled hypertension (per the Investigator's discretion)
- •Class III or IV cardiovascular disease according to the New York Heart Association's (NYHA) Functional Criteria (see APPENDIX C: New York Heart Association's Functional Criteria).
- •Myocardial infarction (MI) within 6 months prior to first study drug administration
- •Patients with a known or suspected hypersensitivity to any of the components of OTS
- •Patients with a known history of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
- •Patients with any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38 degrees within 1 week prior to first study drug administration.
- •Patients with inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 4 weeks prior to first study drug administration.
- •Patients with any other life-threatening illness, significant organ system dysfunction, or clinically significant laboratory abnormality, which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug.
- •Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies.
- •Patients with the inability or with foreseeable incapacity, in the opinion of the Investigator, to comply with the protocol requirements.
- •Any anti-neoplastic agent or monoclonal antibody therapy for the primary malignancy (standard or experimental) within 2 weeks prior to first study drug administration.
- •Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment. If acute symptoms of radiation have fully resolved, the extent and timing of radiotherapy for eligibility can be discussed between Investigator and Sponsor.
- •Patients requiring surgery for the primary or metastatic primary malignancy.
- •Herbal preparations or related over the counter (OTC) preparations/supplements containing herbal ingredients within 1 week prior to first study drug administration and during study.
- •Systemic hormonal therapy which is not related to breast cancer treatment (standard or experimental) within 1 week prior to first study drug administration and during study. The following therapies are allowed:
- •Hormonal therapy (e.g., Megace) for appetite stimulation
- •Nasal, ophthalmic, inhaled, and topical glucocorticoid preparations
- •Oral replacement glucocorticoid therapy for adrenal insufficiency
- •Low-dose maintenance steroid therapy for other conditions (excluding steroid tapers for brain edema/metastases/radiation)
- •Hormonal contraceptive therapy (for WOCBP must be combined with non-hormonal contraceptive equivalent to a double-barrier method)
- •Any other investigational treatments during study. This includes participation in any medical device or therapeutic intervention clinical trials.
- •Dose expansion Cohort for TNBC
- •Patients with only lesions that cannot be safely accessed for biopsy.
结局指标
主要结局
maximum tolerated dose (MTD)
To determine the maximum tolerated dose (MTD) of OTS167 administered via oral capsule (PO) to patients with relapsed or refractory locally advanced or metastatic breast cancer.
次要结局
未报告次要终点
研究者
相似试验
进行中（未招募）
1 期
Phase II Trial with Safety Run-in of MEK Inhibitor AS703026 in Subjects with Poor Prognosis Acute Myeloid Leukemia and Other Hematological Malignancies - AS703026 in Hematological MalignanciesEUCTR2009-010866-49-FRMerck Serono S.A. - Geneva
进行中（未招募）
1 期
A phase I/II trial of selumetinib in combination with anti-retroviral therapy for AIDS-associated Kaposi's sarcomaEUCTR2011-003099-35-GBSheffield Teaching Hospitals NHS Foundation Trust37
已完成
1 期
Phase-I Clinical Trial to study the Safety of oral drug Bioplatin in patients of Advanced metastatic Solid Tumours and those who are resistant to conventional treatmentsCTRI/2017/06/008778Rasayani Biologics Pvt Ltd14
终止
1 期
Study of oral MEK inhibitor selumetinib (AZD6244 hyd-sulphate) in combination with highly active anti retroviral therapy (HAART) in AIDS-associated Kaposi's sarcoma (KS)CancerSarcomaKaposi's sarcomaISRCTN24921472Sheffield Teaching Hospitals NHS Trust (UK)19
招募中
1 期
Phase I Study of MELK Inhibitor to Treat Patients With Advanced Breast Cancer and Triple Negative Breast CancerRelapsed/Refractory Locally Advanced or Metastatic Breast Cancer and Triple Negative Breast CancerJPRN-jRCT2031230090Manabu Ishizuka70