An Multi-center, Open-label Phase Ib/II Study of Gentuximab Injection + Paclitaxel in Patients With Advanced Gastric or Gastroesophageal Junction Cancer to Evaluate Tolerability, Safety, Efficacy and Pharmacokinetics.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 12
- 主要终点
- AEs or SAEs
研究概览
简要总结
The objective of the study is to evaluate Tolerability, Safety, and primary Efficacy of Gentuximab Injection at different dosage in combination with Paclitaxel in Advanced Gastric or Gastroesophageal Junction Cancer patients, to ensure adequate treatment dosage for further study. Meanwhile, the study also evaluate Pharmacokinetics of Gentuximab Injection at different dosage in combination with Paclitaxel.
详细描述
The study includes dose-limiting toxicity （DLT）observing period and randomization period with two cohorts as low-dose group（Gentuximab Injection 8mg/kg+ paclitaxel） and high-dose group（Gentuximab Injection 12mg/kg+ paclitaxel）. During the study，the anti-cancer efficacy, safety and anti-drug antibody were evaluated in all patients. DLT observation is only to subjects enrolled in DLT observation period and it lasts one treatment period. PK were doing in part of subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject can understand the process and methods of the study, complete the study in accordance with the protocol and is willing to sign a written informed consent.
- •Male or female. aged between 18 and 75 years
- •Histopathologically confirmed advanced advanced gastric or gastroesophageal junction cancer, and Documented progression during first-line fluoropyrimidine- and platinum- containing chemotherapy, or during the 3 months following the last cycle of such chemotherapy (or during the 6 months following the last dose of adjuvant therapy or new adjuvant therapy containing fluoropyrimidine and platinium).
- •At least one Measurable lesion.
- •ECOG Performance status (PS) score, 0-1 level.
- •A life expectancy of >3 months.
- •Adequate hematologic function, as defined by: Absolute neutrophil count (ANC) ≥1.5×109/L; hemoglobin concentration ≥90g/L (allowing blood transfusion); and platelet count ≥80×109/L.
- •Adequate hepatic function, as defined by: ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN (liver metastases patients ALT ≤ 5 × ULN, AST ≤ 5 × ULN, TBIL ≤ 3 × ULN).
- •Adequate renal function, as defined by: serum creatinine level≤ 1.5 × ULN, or creatinine clearance ≥ 50ml / min when serum creatinine level> 1.5 × ULN.
- •Adequate coagulation function, as defined by: International normalized ratio (INR) ≤1.5× ULN, activated partial thromboplastin time (aPTT) ≤1.5 x ULN.
- •24-hour urine protein quantitation is <1g（24-hour urine protein quantitative test should be performed when urine protein ≥1+ is found during screening visit）.
- •Subjects (male and female) who have fertility must agree to use reliable contraceptive methods during the trial and in 3 months after the last administration. Female subjects in childbearing age must be negative for blood pregnancy test prior to enrollment.
排除标准
- •Previously administrated with anti-angiogenic drugs or paclitaxel.
- •Systematic anti-tumor therapy (non-anti-angiogenic drugs or paclitaxel) such as chemotherapy, radiotherapy, macromolecular targeted therapy, immunotherapy, endocrine therapy, etc. within 4 weeks before the first dose of investigational drug, except for the following: nitrourea or mitomycin C is within 6 weeks before the first dose, oral fluorouracil and small molecule targeted drugs are within 2 weeks or 5 half-life of the drug(whichever is longer) before the first dose，Chinese medicine with anti-cancer indications is within 2 weeks before the first dose.
- •Has participated in a clinical study of a non-approved experimental agent within 4 weeks prior to screening visit.
- •Has undergone major surgery within 4 weeks before screening visit (not including needle biopsy)， or would undergo planned surgery during the study.
- •Subject with positive HCV-Ab, Anti-HIV or TP-Ab, or positive HBS-Ag with copies of HBV DNA > ULN.
- •Patients with previously confirmed malignant tumors.
- •History of arterial thrombosis or deep vein thrombosis within 6 months prior to screening, or a bleeding event no less than Grade level 3 within 2 months prior to screening， or the investigator determines that there is a risk of bleeding.
- •History of severe cardiovascular and cerebrovascular diseases.
- •Subjects with confirmed brain tumor metastases，but subjects in steady situation can be enrolled.
- •Active bleeding confirmed by gastroscopy when fecal occult blood positive (only subjects with primary lesions not removed need to do fecal occult blood test.
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 12 months before screening visit.
- •Thoracic，abdominal or pericardial effusion that cannot be controlled by repeated drainage or with obvious symptoms.
- •Has a nonhealing wound, serious ulcer, or unrecovered bone fracture.
- •Active infections requiring systemic treatment, including but not limited to active tuberculosis.
- •Using anticoagulation and antiplatelet drugs.
- •Female subjects who is pregnant (confirmed by urine or serum pregnancy test) or lactating.
- •Has a known serious allergy reaction to recombination monoclonal antibody (MAb) drug, ,or infusion reaction.
- •Has known alcohol or drug dependency.
研究组 & 干预措施
2 Gentuximab+ Paclitaxel
12 mg/kg Gentuximab administered intravenously (IV) on D1 and D15（28 days every cycle）+ 80 mg/m² paclitaxel administered IV on D1, D8 and D15
干预措施: Paclitaxel (Drug)
1 Gentuximab+ Paclitaxel
8 mg/kg Gentuximab administered intravenously (IV) on D1 and D15（28 days every cycle）+ 80 mg/m² paclitaxel administered IV on D1, D8 and D15
干预措施: Paclitaxel (Drug)
1 Gentuximab+ Paclitaxel
8 mg/kg Gentuximab administered intravenously (IV) on D1 and D15（28 days every cycle）+ 80 mg/m² paclitaxel administered IV on D1, D8 and D15
干预措施: Gentuximab (Drug)
2 Gentuximab+ Paclitaxel
12 mg/kg Gentuximab administered intravenously (IV) on D1 and D15（28 days every cycle）+ 80 mg/m² paclitaxel administered IV on D1, D8 and D15
干预措施: Gentuximab (Drug)
结局指标
主要结局
AEs or SAEs
时间窗: Baseline through Study Completion, about 24 weeks
Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)
Dose-limiting toxicities (DLT)
时间窗: Up to 4 Weeks
Number of Participants With One or More Drug-Related Adverse Events (AEs) defined as DLT in the protocol
次要结局
- Area Under the Concentration-Time Curve (AUC)(Cycle 1(day1-day 15)& Cycle 2(day 15-day26) & Cycle 3(day 1) Cycle 1(day1-day 15)& Cycle 2(day 15-day26) & Cycle 3(day 1) （28 days for every cycle）)
- Objective response rate（ORR）(Up to 6 cycles (28 days for every cycle))
- Time-to-progress (TTP)(Up to 6 cycles (28 days for every cycle))
- Anti-drug antibody(Up to 6 cycles (28 days for every cycle))
- Progression-free survival (PFS)(Up to 6 cycles (28 days for every cycle))
- Disease control rate (DCR)(Up to 6 cycles (28 days for every cycle))
- Time-to-failure (TTF)(Up to 6 cycles (28 days for every cycle))
- Pharmacokinetics Cmax(Cycle 1(day1-day 15)& Cycle 2(day 15-day26) & Cycle 3(day 1) (28 days for every cycle))