Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Biomarker/Laboratory analysis, Treatment Completed 18 and over Other LUD2004-015 NCT00293215

Trial Description

Summary

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.

Further Study Information

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.

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed malignant solid tumor that has progressed following standard therapy, or for which no standard effective treatment is available

• Tumour expresses Lewis Y antigen (>/= 20% tumour cells positive for Lewis Y by immunohistochemistry assay)

• Measurable disease (RECIST), including at least one lesion >/=2 cm and suitable for 18F-FDG PET imaging

• Eastern Cooperative Oncology Group (ECOG) performance status = 0 or 1

• Life expectancy of >/= 18 weeks

• Recovered from toxicity of any prior therapy

• Renal test: serum creatinine </= 1.5 x ULN

• Hepatic tests: alanine aminotransferase (ALT) </= 2.5 x ULN and total bilirubin </= 1.5 x ULN

• Pancreatic tests: amylase < 1.5 x ULN and lipase </= 1.5 x ULN

• Bone marrow tests: absolute neutrophil count (ANC) >/= 1.5 x 10^9/L; platelet count >/= 150 x 10^9/L

• For women of child bearing potential: a negative serum pregnancy test result within 48 hours before the first dose of CMD-193.

• Willing and committed to use of reliable method of birth control for the study duration and for 28 days after the last dose of CMD-193

• Will refrain from breast feeding infants during study or within 28 days after the last dose of CMD-193

• Signed and dated informed consent

Exclusion Criteria:

• Chemotherapy, radiotherapy, other cancer therapy, or investigational agents within 21 days prior to the first dose of CMD-193

• Symptomatic or clinically active CNS metastases. (Treated CNS metastases permitted if stable and no treatment required for at least 3 months prior to the first dose of CMD-193)

• Significant prior allergic reaction to recombinant human or murine proteins

• History of cirrhosis, current or chronic hepatitis B or C infections, or other significant active liver disease

• Unstable or serious concurrent medical conditions. (Including, but not limited to: gastrointestinal bleeding, hepatitis, significant immune disorders, pancreatitis, congestive heart failure, unstable angina, recent myocardial infarction, ongoing maintenance therapy for life-threatening ventricular arrhythmia, serious active infections, uncontrolled major seizure disorder)

• Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.

• Any other condition that is judged to substantially increase the risk associated with the subject’s participation in this study.

Trial Contact Information

Trial Lead Organizations/Sponsors

Ludwig Institute for Cancer Research

A/Prof. Andrew M Scott, MBBS MD DDU

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00293215
Information obtained from ClinicalTrials.gov on May 27, 2008