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A Phase I Biodistribution Study of 111-Indium-CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen

Phase 1
18 Years
Not Enrolling

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Trial Information

A Phase I Biodistribution Study of 111-Indium-CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen

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

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

Additional infusions of CMD-193 may be administered for patients who have tolerated CMD-193
treatment and if there is evidence of response.

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
- Hepatic tests: alanine aminotransferase (ALT) 1.5 x ULN

- Pancreatic tests: amylase < 1.5 x ULN and lipase
- 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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Biodistribution of CMD-193 based on gamma camera images.

Principal Investigator

A/Prof. Andrew M Scott, MBBS MD DDU

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ludwig Institute for Cancer Research


Australia: Department of Health and Ageing Therapeutic Goods Administration

Study ID:




Start Date:

February 2006

Completion Date:

May 2007

Related Keywords:

  • Neoplasms
  • Neoplasms