A Preliminary Clinical Study on the Pharmacokinetics and Safety of Recombinant Anti-EGFR Human Mouse Chimeric Monoclonal Antibody Injection (CDP1) in Patients With Advanced Colorectal Cancer or Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Pharmacokinetic Parameters: Area Under the Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Infusion
研究概览
简要总结
Colorectal cancer (CRC) is one of the most common human malignant tumors. The incidence and mortality of colorectal cancer in our country are on the rise. Surgery-based, combined with chemotherapy, radiotherapy comprehensive treatment, is the main treatment of colorectal cancer. Surgical resection has been recognized as the primary treatment of colorectal cancer. However, due to the majority of patients already advanced at the time of diagnosis, some difficulties are brought to radical surgery. Therefore, the importance of chemotherapy for colorectal cancer gradually been clinically recognized, But rarely survive more than 18 months." In addition to chemotherapy, there is now a more ideal model of cancer treatment- molecular targeted therapies, including monoclonal antibody drugs such as cetuximab, as well as small molecule tyrosine kinases Inhibitors gefitinib and so on. Molecular targeted drugs make use of the difference in molecular biology between tumor cells and normal cells. Targeting drugs to tumor cells and inhibiting the growth and proliferation of the cells can achieve the therapeutic effect, which has the advantages of high specificity and low adverse reaction. The bio-targeted drug cetuximab is the first drug approved to marketed as an epidermal growth factor receptor (EGFR)-targeting immunoglobulin 1（IgG1）monoclonal antibody. Cetuximab, either monotherapy or combined radiotherapy and chemotherapy, can exert excellent anti-tumor activity in EGFR-positive malignant tumors and can significantly enhance the efficacy of radiotherapy and chemotherapy.
Reference to cetuximab injection, guilin sanjin Co., Ltd. and dragonboat Co., Ltd. jointly developed a recombinant anti-EGFR human mouse chimeric monoclonal antibody (R & D code: CDP1).The primary structure of CDP1 is exactly the same with cetuximab, the higher structure and Physical and chemical properties and cetuximab are highly similar. Pharmacodynamic activity in vivo and in vitro, pharmacokinetic characteristics and toxicological reactions are also similar to cetuximab. CDP1 selected with cetuximab consistent formulations, prescriptions, specifications.
CDP1 was approved by China Food and Drug Administration (No. 2016L06884) in August 2016 for clinical studies. According to the contents of the document and guidelines for biological analogs, the clinical pharmacokinetic and clinical effectiveness comparison tests of CDP1 and the safety and immunogenicity assessment are planned.
详细描述
OBJECTIVES:
Primary:
To compare the pharmacokinetic characteristics of a single dose between CDP1 and the original drug Erbitux In patients with advanced metastatic colorectal cancer.
Secondary :
- To compare the safety and immunogenic characteristics of the single dose between CDP1 and the original drug Erbitux in patients with advanced metastatic colorectal cancer.
- To evaluate the pharmacokinetics and safety of CDP1 multiple administrations."
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
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Age 18 ~ 75 (inclusive) years , male.
- •Histologically or cytologically confirmed ras genotype is wild-type patients with advanced metastatic colorectal cancer, at least second-line chemotherapy (including oxaliplatin, irinotecan and fluorouracil drugs) failed, or intolerant to Irinotecan or chemotherapy-denied patients.
- •ECOG physical score 0-2 points.
- •Expected survival time of 3 months or more.
- •According to RECIST 1.1, there is at least one assessable tumor lesion.
- •No serious hematological system, liver function, renal function and coagulation dysfunction:Neutrophils ≥1.5 × 109 / L, platelets ≥75 × 109 / L, hemoglobin≥90g / L; total bilirubin≤1.5 times ULN, alanine aminotransferase (ALT)≤2.5 times ULN,aspartate transaminase (AST) ≤2.5 times ULN (liver metastasis ALT ≤ 5 times ULN, AST≤ 5 times ULN);Serum creatinine ≤1.5 times ULN;Activated partial thromboplastin time (APTT) ≤1.5 times ULN, prothrombin time (PT) ≤1.5 times ULN, international normalized ratio (INR) ≤1.5 times ULN.
- •Eligible patients with fertility must agree to use reliable methods of contraception (hormonal or barrier abstinence) for at least 12 weeks during and after the last dose of medication.
- •Subjects should be informed of the study prior to the test and voluntarily sign a written informed consent form.
排除标准
- •Chemotherapy, biotherapy, radiation therapy, endocrine therapy, small molecule targeted therapies and other anti-tumor, etc. within 4 weeks prior to the start of study drug use or within 5 half-lives of the known drug (whichever is longer) Anti-cancer therapy, or other experimental drug treatment (except nitrosourea, mitomycin C and fluorouracil oral drugs),nitrosourea or mitomycin C for 6 weeks. Fluorouracil-based oral medications, such as tiotropium and capecitabine, have an interval of at least 2 weeks between the last oral dose and study drug use.
- •Have previously received anti-EGFR monoclonal antibody treatment.
- •EGFR antibody drug-resistant antibody (ADA) positive.
- •Within 3 months prior to enrollment, major organ surgery (excluding biopsy) or significant trauma occurred.
- •The adverse reactions of previous anti-tumor therapy have not been restored to CTCAE 4.03 grade ≤1 (excluding hair loss).
- •Untreated or clinically symptomatic brain metastases, spinal cord compression, cancerous meningitis, or other evidence that the patient's brain, spinal metastases have not yet been controlled, the researchers judged not suitable for inclusion. clinical symptoms suspected brain or soft Membrane disease is to be ruled out by CT / MRI examination.
- •Uncontrolled active infections.
- •Have a history of immunodeficiency, including HIV antibody test positive.
- •Treponema anti-positive.
- •Chronic hepatitis B virus (HBV) infection; Hepatitis C virus (HCV) infection.
- •Serious history of cardiovascular disease: including ventricular arrhythmias requiring clinical intervention; acute coronary syndromes, congestive heart failure, stroke or other cardiovascular events of grade III and higher within 6 months; New York, USA Heart Association (NYHA. Cardiac function grade ≥II or Left ventricular ejection fraction(LVEF) <50%; poorly controlled hypertension (systolic blood pressure> 150 mmHg, diastolic blood pressure> 90 mmHg).
- •Interstitial lung disease.
- •There are other serious history of systemic diseases, the researchers judged not suitable for clinical trials of patients.
- •Alcohol or drug dependence is known.
- •Persons with mental disorders or poor compliance.
- •Moderate or severe infusion-related reactions, including anaphylaxis, have been reported in the past when using monoclonal antibody drugs.
- •The investigators did not find it appropriate to participate in this clinical study because of any clinical or laboratory abnormalities or other causes.
研究组 & 干预措施
anti-EGFR monoclonal antibody
Recombinant anti-EGFR human mouse chimeric monoclonal antibody injection 250mg/m2 single administration
干预措施: anti-EGFR monoclonal antibody (Drug)
Cetuximab injection
Cetuximab,Erbitux 250mg/m2 single administration
干预措施: Cetuximab injection (Drug)
结局指标
主要结局
Pharmacokinetic Parameters: Area Under the Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) After First Infusion
时间窗: Up to 59 Days
Single-dose Phase: Pharmacokinetic parameters: AUC(0-t) for CDP1
次要结局
- Pharmacokinetic parameters: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-00) After First Infusion(Up to 59 Days)
- Physical examination: height(Up to 73 Days)
- Number of Subjects With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score(Up to 73 Days)
- Frequency of adverse events (AE)(Up to 59 Days)
- Immunogenicity indicators: Anti-drug antibodies (ADA) .(Up to 73 Days)
- Pharmacokinetic parameters: Mean Residence Time of Drug in the Body (MRT) of CDP1 After First Infusion(Up to 59 Days)
- Pharmacokinetic parameters: Apparent Terminal Half-life (t1/2) of CDP1 After First Infusion(Up to 59 Days)
- Pharmacokinetic parameters: Observed Maximum Serum Concentration (Cmax) of CDP1 After First Infusion(Up to 59 Days)
- Vital signs: Pulse rate(Up to 73 Days)
- Physical examination: Weigh(Up to 73 Days)
- Number of Subjects With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Best Post-baseline Score(Up to 73 Days)
- Vital signs: Blood pressure(Up to 73 Days)
- Vital signs: Respiratory rate(Up to 73 Days)
- Pharmacokinetic parameters: Total Body Clearance of Drug From Serum (CL) After First Infusion(Up to 59 Days)
- Immunogenicity indicators: neutralizing antibodies(Up to 73 Days)