A Phase 1 Single Dose Escalation Trial of ch806 in Patients With Advanced Tumours Expressing the 806 Antigen
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Number of Patients With Adverse Events
研究概览
简要总结
The purpose of this clinical trial is to describe the toxicity, biodistribution, pharmacokinetics and tumour uptake of a single infusion of ch806 (tagged with a trace amount of radioactive 111-Indium: 111In-ch806) in patients with advanced tumours expressing the 806 antigen.
详细描述
This clinical research study explores the activity of the new experimental antibody ch806 in humans for the first time.
Cancers arising from an organ can be cured in some cases with various combinations of surgery, chemotherapy and radiotherapy. However, once some cancers spread to other organs, treatment with commonly used methods is unlikely to cure the cancer and so treatment is then designed to control the growth of the cancer, and the problems it is causing. One newer treatment approach involves targeting a marker (antigen) called the epidermal growth factor receptor (EGFR), which is found on the tumour cell's surface, with a specially constructed monoclonal antibody (mAB) called "ch806".
Antibodies are proteins that are found in the blood. Antibodies normally protect us from foreign invaders, such as bacteria or viruses. They help destroy these foreign substances by binding to them and activating white blood cells or blood proteins, resulting in their destruction. Tumour cells also have antigens which can be targeted by antibodies. A receptor expressed in high amounts (over-expressed) on various cancer cells, called the epidermal growth factor (EGFR), has been identified, studied and targeted with a variety of antibodies.
One of these antibodies, monoclonal antibody 806 (mAb806), was originally made from mouse protein. Because mAb806 is a mouse antibody, if it were given to humans the body would see it as a foreign protein and would be likely to react to it with an unwanted immune response. To overcome this, the structure of the original mouse antibody called mAb 806 was changed to appear more "human-like" and the chimeric antibody (part mouse part human) called ch806 was produced.
The study is open to patients whose tumour is shown to express the 806 antigen by a special test. Further tests are required to determine eligibility for the study. These tests determine general health and include: physical examination; blood samples for routine tests; routine tests to determine the extent of tumour prior to starting treatment with 111In-ch806 (eg. X-ray, CT scan, etc.).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Patients with advanced or metastatic tumours which are positive for 806 antigen expression based on chromogenic in situ hybridization (CISH) or immuno-histochemistry (IHC) of archived tumour samples.
- •Histologically or cytologically proven malignancy.
- •Measurable disease on CT scan with at least one lesion >/= 2 cm diameter (to allow adequate imaging).
- •Age greater than or equal to 18 years.
- •Karnofsky performance scale >/=
- •Within the last 2 weeks vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified: Neutrophil count >/= 1.5 x 10^9/L; Platelet count >/= 150 x 10^9/L; Serum bilirubin < 34 micromol/L; Creatinine clearance > 50ml/min
- •Able and willing to give valid written informed consent.
排除标准
- •Untreated active metastatic disease to the central nervous system (new or enlarging lesions on CT or MRI), or within 3 months of treatment (i.e. surgery or radiotherapy) for brain metastases. Primary central nervous system tumour (e.g. Glioblastoma Multiforme) is not an exclusion criterion.
- •Other serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders.
- •Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
- •Clinically significant cardiac disease (New York Heart Association Class III/IV).
- •Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
- •Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
- •Lack of availability for immunological and clinical follow-up assessments.
- •Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
- •Pregnancy or breastfeeding.
- •Women of childbearing potential: Refusal or inability to use effective means of contraception.
- •Concomitant treatment with systemic corticosteroids except for patients with Glioblastoma. (Topical or inhalational corticosteroids are permitted.)
- •Prior administration of monoclonal antibody or antibody fragment, and positive human anti-chimeric antibody (HACA) titre.
研究组 & 干预措施
Cohort 3
Patients received a single infusion of 20 mg/m2 111In-ch806 on Day 0 and followed for 30 days post infusion.
干预措施: ch806 (Biological)
Cohort 4
Patients received a single infusion of 40 mg/m2 111In-ch806 on Day 0 and followed for 30 days post infusion.
干预措施: ch806 (Biological)
Cohort 2
Patients received a single infusion of 10 mg/m2 111In-ch806 on Day 0 and followed for 30 days post infusion.
干预措施: ch806 (Biological)
Cohort 1
Patients received a single infusion of 5 mg/m2 111In-ch806 on Day 0 and followed for 30 days post infusion.
干预措施: ch806 (Biological)
结局指标
主要结局
Number of Patients With Adverse Events
时间窗: 30 days
All AEs occurring during the study were documented on the respective case report form (CRF) pages. Events, which occurred after signed informed consent, but before first administration of study drug, were documented on the Pre-existing Signs and Symptom page. Thereafter, they were documented on the Adverse Event page. Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Documentation of AEs includes: date and time of onset and resolution, severity, frequency, seriousness, related interventions and outcome. Dose limiting toxicity (DLT) was defined as any Grade 2 or greater allergic reaction related to 111In-ch806 antibody protein, and any Grade 4 haematological or Grade 3 or greater non-haematological toxicity except for skin rash, occurring within 30 days of the 111In-ch806 infusion.
次要结局
- Mean Normal Organ Dosimetry of 111In-ch806 Using Normal Organ Absorbed Dose (mGy/MBq) Following the First Infusion.(Day 0 (1-4 hours after 111In-ch806 infusion), and on Day 1, Day 2 or 3, Day 4 or 5, and Day 6 or 7 following 111In-ch806 infusion.)
- Mean Volume of the Central Compartment (V1) of 111In-ch806 Following the First Infusion.(Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.)
- Number of Patients With Tumour Uptake of 111In-ch806 Based on Qualitative Assessment of Biodistribution Images and Dosimetry Following the First Infusion.(Day 0 (1-4 hours after 111In-ch806 infusion), Day 1, Day 2 or 3, Day 4 or 5, and Day 6 or 7 following 111In-ch806 infusion.)
- Number of Subjects With Best Overall Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)(30 days)
- Biodistribution of 111In-ch806 Using Whole Body Clearance Methodology or Biological Halftime (T1/2-biol) Following the First Infusion.(Day 0 (1-4 hours after 111In-ch806 infusion), and on Day 1, Day 2 or 3, Day 4 or 5, and Day 6 or 7 post 111In-ch806 infusion.)
- Mean Half-life as Measured by Half-life of Initial Phase of Disposition (T½α) and Terminal Phase of Distribution (T½β) of 111In-ch806 Following the First Infusion .(Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.)
- Mean Total Serum Clearance (CL) of 111In-ch806 Following the First Infusion.(Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.)
- Mean Area Under the Serum Concentration Curve (AUC) of 111In-ch806 Following the First Infusion.(Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.)
- Number of Patients With Human Anti-chimeric ch806 Antibodies (HACA)(30 days)