Clinical trial NCT00199797
Conditions: Colorectal Cancer
Keywords: Colorectal Cancer huA33 antibody chemotherapy
Sponsor: Ludwig Institute for Cancer Research
Start date: 2005-04-18; Completion date: 2016-04-01
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Although treatment for metastatic colorectal cancer has improved significantly over the recent years, it still remains a significant health problem representing the leading cancer by incidence in the United States of America. In the search for new therapies, monoclonal antibodies have been developed to specifically target human colon cancer cells. huA33 is an antibody that reacts with the A33 antigen which is produced by colorectal cancers. Prior studies have shown that administration of the huA33 antibody may delay the growth of tumor cells producing the specific antigen. Oxaliplatin and 5-fluorouracil (5-FU) are cytotoxic agents which are considered as standard treatment in metastatic colorectal cancer. Leucovorin (folinic acid) is a vitamin which enhances the effect of 5-FU. Eligible patients with advanced colorectal cancer will receive huA33 10 mg/m2 by intravenous (IV) infusion weekly for twelve weeks. Starting on Study Day 15 (week 3), 5-FU, leucovorin, and oxaliplatin will be administered every 2 weeks for 10 weeks. Patients will be evaluated weekly for toxicity. Blood samples will be obtained every week for hematology and serum biochemistry analysis and for determination of human anti-human antibodies (HAHA). In patients with measurable disease, tumors will be assessed by the appropriate scan at baseline and at the end of the thirteen week cycle. The primary objective of this study is to assess the safety of huA33 + 5-FU + leucovorin + oxaliplatin. The secondary objective is to measure the immunogenicity of huA33 when given in combination with 5-FU plus leucovorin and oxaliplatin and to document tumor responses.

Detailed description:
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 5-FU.

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. Starting on day 15 and continuing every second week, oxaliplatin, 5-FU and leucovorin are administered. Oxaliplatin and leucovorin will be given as infusions over 2 hours. Afterwards patients will receive a 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 a bolus infusion and 600mg/m2 as a 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 and 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 extent of the disease will be done at the start and at week 13, which is considered to be the first day of the next cycle. Patients may continue with this treatment for up to 2 cycles.

Arms: arm 1: huA33 was administered intravenously over a period of 30 minutes once a week at a dose of 10 mg/m2 for 12 weeks.

Starting on day 15 and continuing every second week, oxaliplatin, 5-fluorouracil (5-FU) and leucovorin were also administered.

Oxaliplatin and leucovorin were given as infusions over 2 hours. Afterwards, patients received a bolus infusion of 5-FU intravenously followed by an infusion of 5-FU over 22 hours.

The doses of oxaliplatin were 85mg/m2, leucovorin 200mg/m2, 400mg/m2 of 5-FU as a bolus infusion and 600mg/m2 as a continuous infusion.

A complete treatment cycle consisted of 12 weeks. Patients were eligible to receive an additional cycle in the absence of dose-limiting toxicity (DLT), immunogenicity (huA33 human anti-human antibodies {HAHA}) and disease progression.
Interventions: intervention 1: Oxaliplatin intervention 2: 5-Fluorouracil intervention 3: Leucovorin intervention 4: huA33
Intervention descriptions: intervention 1: Oxaliplatin was administered at 85 mg/m2 on day 2 of every 2 week regimen. intervention 2: The dose of 5-FU was 400 mg/m2 IV bolus followed by continuous IV infusion at 600 mg/m2 over 22 hours on day 2 and day 3 of every 2 week regimen. intervention 3: Leucovorin was administered at a dose of 200mg/m2 on day 2 and day 3 of every 2 week regimen. intervention 4: huA33 was administered intravenously over a period of 30 minutes once a week at a dose of 10 mg/m2.

Protocol documents: