Clinical Studies by Using Alphacait to Screen Drug Combinations for Advanced Solid Tumor
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Progression-free survival(PFS)
研究概览
简要总结
This is a single-center, open-label, single-arm, non-randomized study designed to evaluate PFS, safety, overall survival (OS), objective response rate (OPR), disease control rate (DCR) and biomarkers of cancer therapy based on Alphacait screening system in subjects with advanced malignant tumor.
详细描述
Tumor heterogeneity leads to a significant difference in the rate of response to drugs in patients with the same pathological type. According to the information, the current initial effective rate of domestic and foreign chemotherapeutic single drug is no more than 30%, even if treated with repeated medication or replacement treatment program, the responsive rate is generally not more than 10%. This heterogeneity of tumor is the biological basis of precision medicine, and how to predict cancer drug sensitivity is a clinical need to solve the practical problems.
Traditional PDX (patient-derived engraft) technology utilizes patient's fresh tumor tissue (containing tumor cells, stromal cells and vascular components), and inoculates in immunodeficient mice to establish mouse tumor model. This method can better reflect the true biological characteristics of tumor, while the mouse tumor tissue can be continuously passed on, and greatly facilitate tumor biology research. According to the transplant site it can be divided into orthotopic transplantation and ectopic transplantation (mostly subcutaneous or renal transplantation). However, the traditional PDX model has its disadvantage of low success rate and time consuming. Most of the tumor matrix after transplantation can be replaced by the corresponding components in mice, leading to differences in the biological properties of the original tumor.
In view of this imperfection, we developed an optimized drug selection model based on the Alphacait screening system that combines artificial intelligence, synthetic lethal and combinational chemistry, which allows rapid selection of candidates from millions of drug combinations. We want to provide physicians with individualized drug therapy through a new in vitro and in vivo drug-sensitive screening technique, to achieve rapid and accurate selection of cancer clinical treatment.
In order to achieve the two key requirements of tumor tissue culture system in vitro, the establishment of tumor microenvironment we introduced the millimeter-sized microbeads, based on combinatorial chemistry in the culture medium. The surface of the microbeads is coated with small molecules that can specifically absorb high levels of metabolites secreted by the tumor cells into the matrix, thereby mimicking in vivo circumstances. In short, we innovatively applied microbeads technology to solve the inherent limitations of 3D organoid culture - no blood circulation in vitro.
Purpose and design Primary endpoint: progression-free survival (PFS) Secondary endpoints: overall survival (OS); disease control rate (DCR), objective response rate (ORR); safety; blood test and gene test in the aspect of biomarkers. Expectations of exploratory markers for this study include the status of exploratory biomarkers associated with immunohistochemistry (IHC) or quantitative reverse transcription polymerase chain reaction (qRT-PCR), a new generation sequencing method (NGS), Nanostring technique and / or other methods to evaluate archived and/or newly acquired tumor tissue, as well as its association with disease status and/or (Including but not limited to somatic mutations and other exploratory markers) according to qRT-PCR and NGS techniques, and to evaluate the relationship between the therapeutic response, the status of the biomarker during exploratory treatment and during treatment, and the evaluation of plasma, serum or whole blood samples (including but not limited to somatic mutations and other exploratory markers) The association of the above markers with disease status and / or therapeutic response.
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
- •Advanced recurrent or metastatic malignant tumor confirmed by pathological diagnosis;
- •At least one measurable malignant lesion;
- •Failed previous standard treatment or with tumor recurrence, and no standard therapeutic regimen available;
- •No radiation therapy within last four weeks or recovered from last radiation related acute complication, if applicable; prophylactic brain radiation therapy or palliative radiation treatment for bone metastasis is acceptable;
- •No gender requirement and must be no younger than18 years old;
- •ECOG PS: score 0-2;
- •Life expectancy more than three months;
- •Patient's organ function level should meet these criteria:
- •(1) CBC should meet these criteria: ANC≥1.5×109 /L，PLT≥100×109/L，Hb≥ 100 g/L; (2) Chemistry should meet these criteria: TBIL<1.5×ULN，ALT、AST< 2.5×ULN（if with liver metastasis ALT、AST<5×ULN） BUN and Cr ≤1×ULN or Cr clearance ≥50ml/min（Cockcroft-Gault formula）
- •Agree to use appropriate contraceptive measure during the study period and until 8 weeks after the last study drug is given. Or patient has been surgically sterilized.
- •Qualified candidate should voluntarily participate this study, sign informed consent forms and be compliant with the study protocols and follow-up visit(s).
排除标准
- •Symptomatic brain metastasis (could still enroll into the study if treatment finished 21 days prior to the enrollment and the patient is stable, but brain MRI, CT or angiogram is needed to rule out no intracranial hemorrhage)
- •Following cardiac disease: second-degree or above cardiac ischemia or myocardial infarction, uncontrolled arrhythmias (including QTc interval male>450 ms, female>470ms), according to NYHA criteria, III to IV cardiac insufficiency, or echocardiogram reveals left ventricular ejection fraction (LVEF) <50%;
- •History of pulmonary interstitial lung disease or active interstitial lung disease;
- •Coagulation dysfunction (INR >1.5 or PT>ULN+ 4sec, or PTT>1.5 ULN), with bleeding tendency or currently receiving thrombolysis therapy or anticoagulation treatment;
- •Clinical bleeding episode or bleeding tendency within past three months, such as GI bleeding, hemorrhagic gastric ulcer, stool guaiac++ positive, or with vasculitis；
- •Arterial or venous thrombosis within last 12 months, such as various types of CVA, DVT or PE patients;
- •Known hereditary or acquired bleeding or hypercoagulable state (such as hemophilia, coagulating dysfunction, thrombocytopenia, hypersplenism);
- •Major surgery, trauma, fracture or ulcer within past 4 weeks;
- •Active infection requiring antibiotics, antifungal or antiviral treatment;
- •Patient has a history of psychiatric medication abuse and cannot be abstinent from the psychiatric medication, or with mental disorder;
- •Participation of other cancer chemotherapy clinical study within past 4 weeks;
- •History of uncured coexisting cancer, no including cured basal cell carcinoma, cervical cancer in situ, or superficial bladder cancer;
- •Pregnant or breast feeding women; fertile patients no willing or able to take effective contraceptive measures;
- •Any circumstances that might affect the proceeding of the clinical trial and/or research result analysis, as determined by the clinical investigator(s).
研究组 & 干预措施
Alphacait-guided therapy
Drugs screened by the Alphacait screening system will be administered in accordance with the protocol of the drug specification or the CPSC guidelines until the patient progresses, intolerant, the patient withdrawn or the investigator determines that the medication must be discontinued.
干预措施: Non Chemotherapy (Drug)
Alphacait-guided therapy
Drugs screened by the Alphacait screening system will be administered in accordance with the protocol of the drug specification or the CPSC guidelines until the patient progresses, intolerant, the patient withdrawn or the investigator determines that the medication must be discontinued.
干预措施: Chemotherapy and target therapy (Drug)
Alphacait-guided therapy
Drugs screened by the Alphacait screening system will be administered in accordance with the protocol of the drug specification or the CPSC guidelines until the patient progresses, intolerant, the patient withdrawn or the investigator determines that the medication must be discontinued.
干预措施: Chinese herb medicine (Drug)
结局指标
主要结局
Progression-free survival(PFS)
时间窗: 36 months
Progression-free survival (PFS) is defined as the time from assignment in the trial to disease progression or death from any cause.
次要结局
- Overall survival(OS)(36 months)
- Overall response rate (ORR)(36 months)
- Disease control rate(DCR)(36 months)
- Incidence of Treatment-Emergent Adverse Events(36 months)
- Biomarkers(36months)