A Phase 1 Study of Recombinant Anti-Epidermal Growth Factor Receptor (EGFR) Human-mouse Chimeric Monoclonal Antibody Injection in Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events [AEs]
研究概览
简要总结
This is an open-label, parallel designed study to assess the pharmacokinetics, safety and tolerability of the single-dose and multi-dose of a recombinant anti-EGFR monoclonal antibody (CPGJ602) in patients with at least one prior chemical regimen failed metastatic colorectal cancer. The immunogenicity and preliminary efficacy of CPGJ602 will also be assessed. The study includes 3 parts: part 1: after a single dose of CPGJ602 or cetuximab (the active comparator), the patients will be observed for 4 weeks; part 2: CPGJ602 or cetuximab will be administered to the patients once a week for 5 weeks; part 3: CPGJ602 will be administered to the patients once a week until the patient's death or the withdrawal decision of the patient and/or investigator.
详细描述
OBJECTIVES:
Primary:
To assess the pharmacokinetics, safety and tolerability of the single-dose and multi-dose of CPGJ602 administered by intravenous infusion.
Secondary:
To assess the immunogenicity and anti-tumor activity of CPGJ602, compare the pharmacokinetics and immunogenicity between CPGJ602 and the active comparator, cetuximab, and to provide scientific basis for the subsequent phase 2/3 clinical trials.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-70 years old, male or female.
- •Histologically or cytologically confirmed metastatic CRC, and have failed (disease progression or intolerance) at least one prior chemical regimen containing oxaliplatin, irinotecan or 5-FU, etc.
- •ECOG performance status 0 or
- •Estimated life expectancy ≥ 3 months.
- •RAS (including K-ras and N-ras) wide type status.
- •Adequate bone marrow, hepatic and renal functions. Hematopoietic:
- •Leukocytes (WBC)>4.0×109/L or Absolute Neutrophil Count (ANC)> 1.5×109/L, Platelet Count (PLT)>80×109/L, Hemoglobin (Hb)>90g/ L; Hepatic: Total Bilirubin (T-Bil)≤1.5×ULT (Upper Limit of Normal), Alanine Transaminase (ALT)/ Aspartate Transaminase (AST)≤2.5×ULT or ≤5×ULT in case of liver metastases; Renal: Blood Urea Nitrogen (BUN)≤1.5×ULT, Serum Creatinine (Cr) ≤ 1.5×ULT.
- •At least one measurable disease based on RECIST criteria (v 1.1).
- •Signed informed consent on a voluntary basis at screening, and no geographical condition that would preclude the study compliance.
排除标准
- •Less than 28 days since prior chemotherapy, radiotherapy or surgery (diagnosis biopsy is allowed).
- •Previous epidermal growth factor receptor (EGFR) targeted therapies (including monoclonal antibody, tyrosine kinase inhibitor [TKI] and other EGFR targeted therapies, such as cetuximab, nimotuzumab, panitumumab, gefitinib, erlotinib, and icotinib, etc.
- •Known hypersensitivity to study drugs or any of the excipients.
- •Known or clinical suspected brain metastases and/or disease of meninges.
- •Clinically significant cardiovascular or cerebrovascular dis ease, history of myocardial infarction (MI) in the latest 6 months, or high-risk of uncontrolled cardiac arrhythmias.
- •History of acute or sub-acute intestinal obstruction, or of inflammatory bowel disease.
- •A serious and uncontrolled concomitant disease which, in the investigator's opinion, rules out the patient's participation in the study, such as history of malignancies other than CRC (with the exception of: curatively treated carcinoma of the skin [except for melanoma]; cured cervical cancer or basal cell skin cancer, ductal carcinoma in situ [DICS], endometrial carcinoma [stage I grade 1]; and other solid tumors including lymphoma without bone marrow infiltration for which the patient has been disease-free for 5 years), uncontrolled hypertension, diabetes mellitus (DM), peripheral neuropathy, and infectious diseases (including viral, bacterial and parasitic infections), etc.
- •Pregnancy or lactation, or a fertility plan during the participation in this study.
- •No more than 4 weeks or no more than 5 times of t1/2 since prior investigational agents.
- •Other situations that impede the patient's participation in the study at the discretion of the investigator.
研究组 & 干预措施
Cetuximab normal dose
Part 1: Cetuximab, IV over 2 hours, 400 mg/m2 X 1. Part 2: Cetuximab, IV, QW, 400 mg/m2 X 1, over 2 hours, followed by 250mg/m2 X4, over 1 hour for each time.
干预措施: Cetuximab (Biological)
CPGJ 602 low dose
Part 1: CPGJ602, IV over 2 hours, 100 mg/m2 X 1;
干预措施: CPGJ602 (Biological)
CPGJ 602 normal dose
Part 1: CPGJ602, IV over 2 hours, 400 mg/m2 X 1; Part 2: CPGJ602, IV, QW, 400 mg/m2 X 1, over 2 hours, followed by 250mg/m2 X4, over 1 hour for each time;
干预措施: CPGJ602 (Biological)
结局指标
主要结局
Incidence of Adverse Events [AEs]
时间窗: Day -28 to 1 month following the last administration
to evaluate the safety and tolerability
Maximum Plasma Concentration [Cmax]
时间窗: Day 0 - Day 21 for single dose and Day 28 - Day 63 for multiple doses
part 1 for single dose and part 2 for multiple doses
Half life of CPGJ602 in blood [t1/2]
时间窗: Day 0 - Day 21 for single dose and Day 28 - Day 63 for multiple doses
part 1 for single dose and part 2 for multiple doses
Area Under the Curve [AUC]
时间窗: Day 0 - Day 21 for single dose and Day 28 - Day 63 for multiple doses
part 1 for single dose and part 2 for multiple doses
次要结局
- Anti-Drug Antibody [ADA](Day 0 to Day 63, and in the follow-up period.)
- Cancer antigen [CA19-9](Day -28 - Day 63)
- Objective Response Rate [ORR](Day -28 - Day 63)
- Carcinoembryonic antigen [CEA](Day -28 - Day 63)