111-In-ch806 in Patients With Advanced Tumours Expressing the 806 Antigen
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Single Dose Escalation Trial of ch806 in Patients With Advanced Tumours Expressing the 806 Antigen|
- Toxicity as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE).
- Biodistribution of ch806 based on gamma camera images.
- Pharmacokinetics of 111In-ch806 and ch806 protein from gamma counting and ELISA of serum samples.
- Tumour uptake of 111In-ch806 based on qualitative assessment of biodistribution images and dosimetry.
|Study Start Date:||May 2005|
|Estimated Study Completion Date:||May 2006|
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 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One of these antibodies, mAb806, was originally made from mouse protein.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 111 In-ch806 (eg. X-ray, CT scan, etc.)
On study, 111In-ch806 is given by infusion into a vein over one hour. Blood samples to determine the amount of drug in the blood (pharmacokinetics), are taken a number of times on the day of the 111 In-ch806 infusion; about every 2nd day for the first week; then 1 week, 2 weeks and 3 weeks after the infusion. Blood tests are also used to monitor general health and to see if the immune system recognises the infused antibody by making another antibody against it. Such a response is called “anti-ch806 antibody” or “HACA”. Gamma camera scans to see where 111 In-ch806 goes in the body are done right after the first infusion, and 3 more times over the next seven days. The scan takes about one hour each time. Visits for weekly follow up examinations and blood tests until 30 days after the infusion are combined with further gamma camera scans. Tumour is reassessed 30 days after the infusion using the same type of scans as at study entry.
Further treatment with a course of 111In-ch806 is not be available at this time, as this study is to test the safety of a single infusion only.
|Ludwig Institute Tumor Targeting Program, Austin Health|
|Heidelberg (Melbourne), Victoria, Australia, 3084|
|Principal Investigator:||A/Prof Andrew M Scott, MBBS MD DDU||Ludwig Institute for Cancer Research|