Phase I Trial of huA33 Plus 5-Fluorouracil (5FU), Leucovorin and Oxaliplatin in Patients With Metastatic Colorectal Cancer
Purpose of the Research Study:
huA33 is an antibody that reacts with the A33 antigen which is produced by colorectal
cancers. Prior studies have shown that application of the huA33 antibody may delay the
growth of tumor cells producing the respective antigen.
Oxaliplatin and 5-FU are cytotoxic agents which are considered as standard treatment in
metastatic colorectal cancer. Leucovorin is a vitamin which enhances the effect of 5FU.
The primary purpose of this study is to determine whether the combination huA33 plus
Oxaliplatin, 5-FU and Leucovorin is safe and what side effects occur.
Description of Research Procedures:
The first step is to determine whether or not patients are eligible for participation in the
study. Apart from general blood tests and x-ray studies needed, this involves testing with
regard to some special requirements:
- Three tests of stool to determine if it is positive for blood.
- Women of childbearing age must have a negative pregnancy test.
- If patients ever had a treatment with similar substances like huA33 before, a blood
sample needs to be tested for antibodies that may have developed against huA33.
After eligibility is established, huA33 will be administered intravenously over a period of
30 minutes once a week at a dose of 10 mg/m2. Every second week, Oxaliplatin, 5-FU and
Leucovorin are administered additionally. Oxaliplatin and Leucovorin will be given as an
infusion over 2 hours. Afterwards patients will receive an bolus infusion of 5-FU
intravenously followed by an infusion of 5-FU over 22 hours.
The doses of Oxaliplatin will be 85mg/m2, Leucovorin 200mg/m2, 400mg/m2 of 5-FU as an bolus
infusion and 600mg/m2 as an continuous infusion. A complete treatment cycle consists of 12
weekly treatment days.
Patients will have an interview with their doctor and a physical examination before the
first day of treatment and before each therapy. Standard blood tests as well as special
blood tests to measure a possible reaction of the immune system to the huA33 antibody will
be done weekly before the treatment is started. The amount of blood to be drawn will be
20-30 ml during one cycle of the study.
X-rays and/or CT scans to measure the extend of the disease will be done at the start and on
week 12, which is considered to be the first day of the next cycle. Patients may continue
with this treatment until there is no evidence of tumor progression.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the safety of the combination of huA33 and 5FU plus leucovorin and oxaliplatin in patients with metastatic colorectal cancer
Duration of study
Christoph Renner, MD
Universitätsspital Zürich, Switzerland
Germany: Federal Institute for Drugs and Medical Devices