Biodistribution Study of CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen
This is a clinical trial of a drug called CMD-193 which is a humanised monoclonal antibody linked to a toxin (calicheamicin). The purpose of this study is to determine in patients with advanced tumours expressing the Lewis-Y antigen:
- How much and how long 111-In-CMD-193 (CMD-193 tagged with a small amount of radioactive Indium – also called Indium-111 or 111In) circulates in the blood, where the antibody goes in the body, and how much attaches to the tumour.
- Whether CMD-193 causes changes in the metabolism (activity) of the tumour.
- Whether CMD-193 causes shrinkage of the tumour.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Biodistribution Study of 111-Indium-CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen|
- Biodistribution of CMD-193 based on gamma camera images.
- Tumour uptake of 111In-CMD-193 based on qualitative assessment of biodistribution images and dosimetry.
- Pharmacokinetics of 111In-CMD-193 and CMD-193 protein from gamma counting and ELISA of serum samples.
- Tumour metabolism response to CMD-193 assessed by 18F-FDG PET.
- Tumour response to CMD-193 measured by RECIST.
|Study Start Date:||February 2006|
|Study Completion Date:||May 2007|
Cancers arising from an organ can be cured in some cases with various combinations of surgery, chemotherapy and radiotherapy. However, once some cancers spread, treatment with conventional methods is unlikely to cure the cancer and treatment is designed to control the growth of the cancer and the problems it is causing. This is a clinical trial of a drug called CMD-193 which is a humanised monoclonal antibody linked to a toxin (calicheamicin). The experimental treatment approach used here involves targeting a marker (antigen) called the Lewis-y antigen on the tumour cell’s surface with a specially constructed humanised monoclonal antibody. This antibody delivers a toxin (calicheamicin) into the tumour cell and this may kill the tumour cell.
This clinical research study explores where CMD-193 distributes in the body, and the activity of CMD-193 in humans. CMD-193 recognises and binds to the Lewis-y antigen which is present on some cancers. If a radioactive label is attached to the antibody, the antibody can be seen in a special type of scan, to seek out and stick to the tumour. Showing how the antibody localizes to tumour may assist in determining optimal dosing for future trials.
This study is open to patients with advanced cancers where tumour samples that were previously removed are shown to express the Lewis-y antigen. A series of tests will be performed to determine eligibility to participate in the trial. Groups of patients will be allocated increasing doses of CMD-193 at study entry to explore the effects in a series of doses.
Patients will each receive 6 infusions of CMD-193 (the first dose will be labeled with a trace dose of radioactive Indium-111 (111In)) at three weekly intervals, unless toxicity, disease progression or withdrawal from study for another reason occurs.
On study, 111-In-CMD-193 will be given intravenously (by infusion into a vein) over one hour. Patients will be observed for three hours after the infusion. An ECG (heart trace) will be performed prior to the first dose of 111-In-CMD-193 and repeated 30 minutes after the infusion. To determine how the body rids itself of CMD-193, blood samples will be taken just before and after the 111-In-CMD-193 infusion, and at three hours after infusion completion: 3 in total. These blood samples will be drawn from a separate intravenous access line which will be placed into a vein. Blood samples will also be drawn on the next day, then approximately every second day for the first week. Special scans to see where 111-In-CMD-193 goes in the body will be done approximately one hour after the first infusion, and 3 more times over the next seven days. The procedure will take about one hour each time.
Further blood tests will be done once per week, coinciding with clinical visits. These samples will check the general health of the blood cells and blood chemistry, and assess blood levels of CMD-193. Blood tests will also see if the immune system recognises the infused antibody by making another antibody against it.
Evaluation of the function (metabolism) of the tumour will also be performed with a special scan called a Positron Emission Tomography (PET) scan. This PET scan will be performed before the first CMD-193 infusion, and after the 2nd and 4th infusions of CMD-193. Tumour assessment will take place before the study with appropriate tests such as CT scans, plain X-rays etc. These scans will be repeated 15-21 days after the 2nd, 4th and 6th infusions of CMD-193.
Additional infusions of CMD-193 may be administered for patients who have tolerated CMD-193 treatment and if there is evidence of response.
|Cancer Care Services, Dept. of Medical Oncology, Royal Brisbane and Women's Hospital|
|Herston, Queensland, Australia, 4209|
|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|