NCT03256331终止1 期
A Phase I, Open-Label, Dose Escalation and Extension Study to Evaluate the Safety, Tolerability and Preliminary Effects of Oral BEL-X-HG in Patients With Advanced Refractory Solid Malignancies
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This is a Phase I, open-label, uncontrolled, multicenter dose escalation and extension study to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate safety / tolerability and preliminary effects of BEL-X-HG in patients with advanced refractory solid tumors. Dose escalation during the study will be made based on dose-limiting toxicity (DLT).
详细描述
This study will be carried out in 2 parts:
Part 1: A sequential Dose Escalation Part of four doses following a 3 + 3 design where dose escalation will be made based on dose-limiting toxicity (DLT), for a single cycle (28-days) of BEL-X-HG treatment
Part 2: A Dose Extension Part of up to 5 cycles (28-days each) at the same dose level (starting dose) of BEL-X-HG treatment
Approximately 24-48 eligible subjects with confirmed advanced refractory solid tumors will be enrolled sequentially, in 3 subject cohorts, from the lower to the higher dose cohort into the study. Escalating dose levels of BEL-X-HG in 4 study cohorts and one modified dose will be as follows:
Cohort 1: Dose level 1 - 0.5 g/day (0.25 g, bid)
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients of age ≥20 years
- •Pathologically or cytologically confirmed advanced refractory solid tumors for which standard therapy proven to provide clinical benefit does not exist or is no longer effective. It is acceptable for HCC subjects with Child Pugh stage A to confirm diagnosis of the advanced refractory solid tumors by imaging (CT scan).
- •Evaluable disease, at least one measurable target lesion on imaging by RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
- •Life expectancy ≥ 3 months
- •Patients able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major restriction of the stomach or bowels
- •Laboratory values at screening and baseline (Day 1) of:
- •Absolute neutrophil count (ANC) ≥ 1,500 /mm3
- •Platelets ≥ 75,000 /mm3
- •Hemoglobin (Hb) ≥ 8.5 g/dL
- •Serum creatinine (Cr.) ≤1.5 mg/dL or estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73 m
- •MDRD Study equation: eGFR = 186 x (SCr)^-1.154 x (age)^0.203 x (0.742 if female) x (1.210 if African American) SCr: serum creatinine in mg/dL; age: in year
- •Patients with primary liver cancer or hepatic metastasis are eligible to enroll, provided that, at screening and baseline (Day 1), the following criteria are met:
- •Total bilirubin (T-Bil) ≤2.0 mg/dL
- •AST and ALT ≤ 5 times the institutional upper limit of normal
- •Child-Pugh Class A; (Score ≤6)
- •Serum albumin ≥2.8 g/dL
- •Patients with a history of esophageal bleeding have varices that have been sclerosed or banded and no bleeding episodes have occurred during the prior 6 months
- •If history of brain metastases treated with radiation therapy, radiation therapy is required to be completed at least 3 months prior to enrolment and metastasis achieve stable disease (SD) since radiation completion
- •Must have recovered from toxicities of previous anti-cancer treatments to NCI-CTCAE version 4.03 grade 1 or lower, except for alopecia
- •Females patient must be either of non-childbearing potential, i.e. surgically sterilized (e.g. tubal ligation, hysterectomy, or ovariectomy) or one year post- menopausal; or, if of childbearing potential, confirmed not pregnant at screening and use of two adequate contraceptive precautions (as per investigator) i.e. condoms plus oral contraceptives or condoms plus endometrial contraceptive devices, during the entire treatment period of this study and for 6 months after exiting from the study
- •Male patients with female partners of childbearing potential must be willing to use a reliable form of contraception (condoms), from screening until 6 months after existing from the study
- •Given signed and dated written informed consent and willing/able to comply with all protocol required visits/procedures
排除标准
- •Primary major surgery < 4 weeks prior to the planned first study treatment day
- •Lactating or pregnant women or plans to be become pregnant
- •Except for alopecia, any drug-related AE from any previous treatments not recovered to NCI-CTCAE version 4.03 grade 1 or lower prior to the planned first study treatment day
- •With active systemic infections, active and clinically significant cardiac diseases, active gastrointestinal diseases, active pulmonary diseases, or medical conditions that may significantly affect adequate absorption of investigational product.
- •Known allergy to BEL-X-HG or its formulation excipients
- •History of autoimmune disease that in the investigator's opinion may be significant to exclude participation in the study
- •Use of any investigational agents or non-registered product within 4 weeks of baseline
- •Known human immunodeficiency virus (HIV) positivity
- •Known hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier who has:
- •serum HBV DNA > 2,000 IU/mL and abnormal ALT (> 5 ULN) (for HBV carrier)
- •abnormal ALT (> 5 ULN) (for HCV carrier)
- •With conditions, judged by the investigator, as unsuitable for the study
- •Mean QTc with Fridericia's correction (QTcF*) greater than 450 ms in screening ECG or history of familial long QT syndrome
- •*: Fridericia's formula:
- •Any cancer-directed therapy (chemotherapy, radiotherapy, biological or immunotherapy, etc.) within 4 weeks or 5 half-lives, (whichever is shorter) of baseline
研究组 & 干预措施
BEL-X-HG
Experimental
3+3 dose escalation
干预措施: BEL-X-HG (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 28 days (first treatment cycle of every subjects)
The prior dose level below the dose level at which ≥2/3 or ≥2/6 subjects suffer dose-limiting toxicity (DLT).
次要结局
- Oxidative stress(up to 168 days (up to 6 cycles of each enrolled subjects))
- Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST)(up to 168 days (up to 6 cycles of each enrolled subjects))
- immunological status(up to 168 days (up to 6 cycles of each enrolled subjects))
- cachexia status(up to 168 days (up to 6 cycles of each enrolled subjects))
- Incidence of Treatment-Emergent Adverse Events(up to 168 days (up to 6 cycles of each enrolled subjects))
- liver function(up to 168 days (up to 6 cycles of each enrolled subjects))
- nutritional status(up to 168 days (up to 6 cycles of each enrolled subjects))
- Quality of life (QoL) of patients with advanced refractory solid tumors(up to 168 days (up to 6 cycles of each enrolled subjects))
研究者
研究点 (2)
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