NCT05625919招募中1 期
A Phase Ⅰb/Ⅱ Multi-center Study of Safety and Efficacy of Sirolimus for Injection (Albumin-bound) in Patients With Advanced Malignant Perivascular Epithelioid Cell Tumor (PEComa)
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.1 个研究点 分布在 1 个国家目标入组 54 人开始时间: 2022年11月8日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR) in phase Ⅱ
研究概览
简要总结
This is a phase Ⅰb/Ⅱ multi-center study of safety and efficacy of Sirolimus for Injection (Albumin-bound) in patients with advanced malignant perivascular epithelioid cell tumor (PEComa).
详细描述
This is a non-randomized, multi-center, open-label, Phase Ⅰb/Ⅱ clinical trial. For phase Ⅰb, patients must have a histologically confirmed diagnosis of advanced soft tissue sarcomas (including malignant PEComa, accounting for at least 1/2) that have failed standard treatment (disease progression or relapse or intolerance, such as chemotherapy, radiotherapy, targeted therapy, etc.) or lack effective treatment. The recommended phase II dose (RP2D) will be determined in phase Ⅰb. For phase Ⅱ, patients must have a histologically confirmed diagnosis of malignant PEComa that is either metastatic or locally advanced and for which surgery is not a recommended option. Phase Ⅱ will use the recommended dose and dosing regimen from Phase Ⅰb.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 years or older, and Phase Ⅰb: Patients with histologically confirmed diagnosis of advanced soft tissue sarcomas (including malignant PEComa, accounting for at least 1/2) have failed standard treatment (disease progression or relapse or intolerance to chemotherapy, radiotherapy, targeted therapy, etc.) or lack effective treatment; Phase Ⅱ: Patients must have a histologically confirmed diagnosis of malignant PEComa that is either metastatic or locally advanced and for which surgery is not a recommended option.
- •[Malignant PEComas displaying 2 or more of the features of large size (> 5 cm), infiltrative growth, high nuclear grade, cellular necrosis, mitoses ≥1/50 high power field (HPF), or vascular invasion]
- •At least 1 measurable lesion as defined by RECIST 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Life expectancy >3 months.
- •Patient must have the following biological parameters levels at screening (without blood transfusion, EPO, G-CSF and other medical support within14 days prior to screening tests):
- •Blood tests: Absolute neutrophil count (ANC) ≥1.5 × 10^9/L; Platelet count ≥100 × 10^9/L; Hemoglobin ≥90 g/L; Renal function tests: serum creatinine ≤1.5 x upper limit of normal (ULN); Liver function tests: Total bilirubin ≤1.5 x ULN (Patients with liver metastases, bile duct obstruction, or confirmed Gilbert syndrome: ≤ 3×ULN); AST and ALT ≤2.5 x ULN (≤5 x ULN if attributable to liver metastases); Blood clotting function tests: INR or PT ≤ 1.5 × ULN; APTT≤ 1.5 × ULN;
- •Fasting serum triglycerides<300 mg/dL(3.42 mmol/L), fasting serum cholesterol < 350 mg/dL ( 9.07mmol/L; ).
- •Fasting blood glucose (FPG) < 7.8 mmol/L and HbA1c < 8%.
- •Women of child-bearing potential, or men whose partners are women of childbearing age must agree to use reliable contraceptive methods during the trial period and at least 6 months after the last administration; women of childbearing age must have a negative serum pregnancy test within 7 days prior to the first administration, should not be breast feeding.
- •Patients must give informed consent to the study prior to the trial and voluntarily sign informed consent form.
排除标准
- •Anti-tumor therapy such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy within 4 weeks prior to the first dose of study drug, with the following special requirements:
- •Nitrosoureas (eg, carmustine, lomustine, etc.) or mitomycin C within 6 weeks prior to the first dose of study drug; Oral fluorouracils and small molecule targeted drugs within 2 weeks or 5 half-lives (whichever is longer) before the first dose of study drug; Traditional Chinese medicines with anti-tumor indications within 2 weeks prior to the first dose of study drug;
- •Received other unmarketed clinical investigational drug within 4 weeks prior to the first dose of study drug.
- •Major surgical procedures within 4 weeks prior to the first dose of study drug or not fully recovered from any previous invasive procedures.
- •Received systemic glucocorticoids (prednisone > 10 mg/day or equivalent doses) or other immunosuppressive therapy within 2 weeks prior to the first dose of the study drug [with the following exceptions: treatment with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term use of glucocorticoids for prophylaxis (eg, prevention of contrast allergy)].
- •Infection that required systemic anti-infective therapy (oral or IV) within 2 weeks before enrollment.
- •Inactivated or live attenuated vaccine or novel coronavirus vaccine within 30 days before the first dose.
- •Use of strong inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study drug, or requiring concomitant treatment during the study.
- •History of other malignancies within 5 years prior to the first dose of the study drug, except in the following cases: cured basal cell or squamous cell skin cancer, superficial bladder cancer, prostatic carcinoma in situ, carcinoma in situ of the cervix, breast carcinoma in situ, etc., or locally curable cancer that has been disease-free for 5 years;
- •Liver-directed therapy is required within 2 months of enrollment. Prior treatment with radiotherapy (including radio-labeled spheres and/or cyberknife, hepatic arterial embolization (with or without chemotherapy) or cyrotherapy/ablation) is allowed if these therapies does not affect the areas of measurable disease being used for this protocol.
- •History of serious cardiovascular disease, such as severe heart rhythm or conduction abnormalities (ventricular arrhythmias requiring clinical intervention, grade Ⅱ or Ш atrioventricular block, etc.). History of myocardial infarction, unstable angina, heart failure, New York College of Cardiology (NYHA) grade Ⅱ and above, and coronary artery bypass surgery within 6 months before the first dose of the study drug; Left ventricular ejection fraction (LVEF) < 50%, QTcF > 450 msec (male) or female QTcF > 470 msec (female), etc.
- •Unresolved toxicity from prior anti-tumor therapy greater than Grade 1 as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.(except for alopecia and any other toxicities that have no safety risk judged by the investigator).
- •Known active uncontrolled or symptomatic central nervous system (CNS) metastases, or other evidence of uncontrollable central nervous system metastases or meningeal metastases that not eligible for inclusion determined by the investigator.
- •Hydrothorax, ascites or pericardial effusion with clinical symptoms or required symptomatic treatment.
- •Patients with angiomyolipoma(AML) or lymphangioleiomyomatosis (LAM).
- •History of serious lung disease, such as interstitial lung disease and/or pneumonitis, or pulmonary hypertension, or pre-existing severely impaired lung function.
- •Pre-existing thyroid abnormality is allowed provided thyroid function can be controlled with medication.
- •Known hypersensitivity or intolerance to any ingredient in the study drug.
- •History of autoimmune disease (except tuberous sclerosis), immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency disease, or history of organ transplantation.
- •Active Hepatitis B or Hepatitis C, or active syphilis infection Active Hepatitis B: HBsAg-positive with HBV DNA titer ≥ 1 × 10^3 IU/mL; Patients are eligible for enrollment if they are HBsAg positive with peripheral blood HBV-DNA < 1 × 10^3 IU/mL if, in the opinion of the investigator, the patient's chronic hepatitis B is in a stable phase and does not increase the subject's risk.
- •Active Hepatitis C: HCV antibodies -positive with HCV RNA-positive; Active syphilis infection: Treponema pallidum antibodies (RPR or TRUST)-positive or presence of syphilis infection requiring systemic therapy.
- •Severe concomitant diseases that endanger patient safety, interfere the compliance of the study procedure (such as uncontrollable hypertension, active gastrointestinal bleeding, etc.) or other reasons that make the patient inappropriate for entry into this study.
研究组 & 干预措施
Sirolimus for Injection (Albumin-bound)
Experimental
Sirolimus for injection (Albumin-bound) will be administered intravenously on day 1and day 8 every 21 days (a cycle).
干预措施: Sirolimus for Injection (Albumin Bound) (Drug)
结局指标
主要结局
Overall response rate (ORR) in phase Ⅱ
时间窗: Up to 2 years
Maximum tolerated dose (MTD)
时间窗: Cycle 1 (Up to 21 days)
Recommended phase 2 dose (RP2D)
时间窗: Cycle 1 (Up to 21 days)
AE and SAE occurrence and frequency in phase Ⅰb
时间窗: Up to 2 years
Dose-limiting toxicities (DLT)
时间窗: Cycle 1 (Up to 21 days)
次要结局
- Duration of Response (DOR)(Up to 2 years)
- Overall response rate (ORR) in phase Ⅰb(Up to 2 years)
- AE and SAE occurrence and frequency in phase Ⅱ(Up to 2 years)
- Peak time (Tmax)(Up to 2 years)
- Disease Control Rate (DCR)(Up to 2 years)
- Progression-free Survival (PFS)(Up to 2 years)
- Area under the plasma concentration versus time curve (AUC)(Up to 2 years)
- Peak Plasma Concentration (Cmax)(Up to 2 years)
- Overall survival (OS)(Up to 2 years)
- Terminal half-life (t½)(Up to 2 years)
研究者
研究点 (1)
Loading locations...
相似试验
尚未招募
1 期
A Study of Sirolimus for Injection (Albumin-bound) in Patients With Advanced Solid TumorsMalignant Solid TumorsNCT05508620CSPC ZhongQi Pharmaceutical Technology Co., Ltd.270
终止
2 期
Topical Sirolimus Ointment for Cutaneous Angiofibromas in Subjects With Tuberous Sclerosis ComplexAngiofibroma of FaceTuberous SclerosisNCT03363763Aucta Pharmaceuticals, Inc24
已完成
3 期
Study of Sirolimus-Coated BX VELOCITY Balloon-Expandable Stent in Treatment of de Novo Native Coronary Artery Lesions (SIRIUS)Coronary Artery DiseaseNCT00232765Cordis Corporation1,058
已完成
2 期
A Phase 2 Study of Nab-sirolimus (ABI-009) in Patients With Advanced Malignant PEComaMalignant PEComaNCT02494570Aadi Bioscience, Inc.34
进行中（未招募）
不适用
Efficacy and Safety of Sirolimus in Active Systemic Lupus ErythematosusSystemic Lupus ErythematosusNCT04582136Chinese SLE Treatment And Research Group146