Dose-escalation, PK- and Safety Study With Single Agent CetuGEX™ in Patients With EGFR Positive Locally Advanced and/or Metastatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- To define the recommended phase II dose and regimen
研究概览
简要总结
This was a prospective, open label, multicenter study evaluating the safety, tolerability and pharmacokinetics of CetuGEX™ after intravenous administration in patients with EGFR positive, locally advanced and/or metastatic solid cancers. The effect of CetuGEX™ on the development of anti-drug antibodies and on tumour response was also evaluated.
详细描述
Male or female patients ≥18 years of age with a histologically confirmed locally advanced and/or metastatic solid organ tumor. Patients enrolled in Germany were required to have a positive EGFR overexpression status. Patients must have experienced a failure or non-availability of standard therapy (had received at least one line of chemotherapy and further standard therapy was not an option at study entry). Open-label, non-randomized, inter-patient dose-escalation, multi-center study. Patients were to receive CetuGEX until disease progression or until intolerable toxicities occurred.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female and age ≥ 18 yrs
- •Histologically confirmed EGFR positive locally advanced and/or metastatic solid organ tumour
- •Measurable or non-measurable tumour
- •Failure of standard therapy or non-availability of standard therapy (Patients must have received at least 1 line of chemotherapy and further standard therapy is not an option at study entry)
- •All anti-tumour therapies must be completed 4 weeks before start of study treatment; treatment with Cetuximab must be completed at least 6 weeks prior to study start
- •ECOG Performance Status ≤1 and estimated life expectancy of ≥ 3 months
- •Adequate organ function:
- •Bone marrow function: hemoglobin ≥ 100 g/L; white blood cell count (WBC) ≥ 3.0 x 10^9/L; absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; platelet count ≥ 100 x 10^9/L
- •Hepatic: aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 2.5 times upper limit of normal (ULN) (≤ 5 x ULN if hepatic metastases present); bilirubin ≤ 1.5 x ULN; alkaline phosphatase ≤ 5.0 x upper limit of normal (ULN)
- •Renal: creatinine < 1.5 x ULN
- •Patients of both genders with procreative potential must use effective contraception while enrolled in the study and for at least 4 weeks after the last study drug infusion
- •Written informed consent must be obtained prior to conducting any study-specific procedures
- •For Expansion Phase only:
- •No prior treatment with Cetuximab allowed
排除标准
- •Chemotherapy, radiation, other anti-cancer therapies including any investigational agents at the study enrolment within 4 weeks prior to study enrolment
- •Concurrent anti-tumour therapy or concurrent immunotherapy
- •Concurrent systemic steroids except topical (inhaled, topical, nasal) or replacement therapy for the last 28 days.
- •Major surgery within 4 weeks prior entering the study and/or incomplete recovery from surgery or planned major surgery
- •Primary or secondary immune deficiency
- •Clinically active infections > CTCAE grade 2
- •Prior allergic reaction to a monoclonal antibody (e.g. Trastuzumab, Cetuximab or Bevacizumab).
- •Active hepatitis B assessed by serology, hepatitis C by histology; human immunodeficiency virus (HIV) seropositivity
- •Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for ≥ 3 years will be allowed to enter the study.
- •Uncontrolled medical condition considered as high risk for the treatment with an investigational drug including unstable diabetes mellitus, vena-cava-syndrome, chronic symptomatic respiratory disease.
- •Clinical signs of brain metastasis or leptomeningeal involvement
- •Symptomatic congestive heart failure (New York Heart Association [NYHA] 3 or 4); unstable angina pectoris within 6 months prior to enrollment; significant cardiac arrhythmia, or history of stroke or transient ischemic attack within 1 year.
- •Active drug abuse or chronic alcoholism
- •Pregnancy or Breastfeeding
研究组 & 干预措施
CetuGEX™, weekly
application weekly
干预措施: CetuGEX™ (Drug)
CetuGEX™ 2-weekly
application biweekly
干预措施: CetuGEX™ (Drug)
结局指标
主要结局
To define the recommended phase II dose and regimen
时间窗: from first infusion until 28±2 days following the last infusion
Defining a recommended dose for a Phase II study was possible based on the available PK data in combination with the safety and activity data for CetuGEX™
Incidence of Treatment-Emergent Adverse Events (TEAE) assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0
时间窗: throughout the study until 28±2 days after last infusion
TEAE were coded by use of Medical Dictionary for Regulatory Activities (MedDRA) version 13.1
Dose-limiting toxicities (DLT)
时间窗: from first infusion until 28±2 days following the last infusion
DLTs were defined as drug-related: * Hematological or non-hematological toxicity grade 3 (excl. rash) or 4 excluding inadequately treated nausea and vomiting; * In case of skin reaction (rash) grade 4
Changes of corrected QT interval (QTc) duration
时间窗: from first infusion until 28±2 days following the last infusion
by use of 12-lead electrocardiograms (ECG)
Incidence of clinically relevant abnormal clinical laboratory parameters
时间窗: from first infusion until 28±2 days following the last infusion
graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0
次要结局
- Anti-Tumor Activity: Confirmed Best Overall Response Rates(From date of randomization until the date of first documented progression, assessed up to 60 months)
- Anti-Tumor Activity: Clinical Benefit Rates(From date of randomization until the date of first documented progression, assessed up to 60 months)
- Eastern Cooperative Oncology Group (ECOG) Performance Status(From date of randomization until 28 days ± 2 days after the end of treatment)
- Pharmacokinetics (PK): Area under the serum concentration-time curve (AUC)(Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks)
- Pharmacokinetics (PK): Maximum serum concentration (Cmax)(Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks)
- Pharmacokinetics (PK): Time to maximum serum concentration (tmax)(Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks)
- Pharmacokinetics (PK): Minimal serum concentration (Cmin)(Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks)
- Pharmacokinetics (PK): Terminal elimination half-life (t1/2)(Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks)
- Pharmacokinetics (PK): Clearance rate (CL)(Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks)
- Pharmacokinetics (PK): Volume of distribution (Vz)(Prior to 1st infusion, end of 1st infusion, 4 hours after end, 72 and 168 hours after start of 1st infusion, then before and after each infusion up to 10 weeks)