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Phase I Trial of Oral Capecitabine Combined With 131I-huA33 in Patients With Metastatic Colorectal Cancer

Phase 1
18 Years
Not Enrolling
Colorectal Neoplasms

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Trial Information

Phase I Trial of Oral Capecitabine Combined With 131I-huA33 in Patients With Metastatic Colorectal Cancer

This clinical trial tests the combination of humanised A33 monoclonal antibody tagged with
radioactive iodine 131 (131I-huA33) together with capecitabine chemotherapy in patients with
advanced colorectal cancer.

When colorectal cancer has spread to other organs, it is generally considered incurable but
with a limited number of treatment options. Colorectal cancer cells express proteins on
their surface known as antigens, and one of these is called the A33 antigen. An antibody
which targets the A33 antigen was initially developed in the mouse and found to bind to
human colorectal cancer cells. Because humans developed immune reactions when given the
mouse antibody, an antibody, which is more like normal human antibodies, was developed
(humanised A33 antibody). In order to increase its effectiveness, radioactive iodine (131I)
has been attached to the antibody so that the antibody can deliver radiation directly to
colorectal cancer cells. Previous studies have shown that both the unlabelled humanised A33
antibody as well as the humanised A33 antibody tagged with radioactive iodine can be
administered safely to humans with no major allergic reactions. The addition of chemotherapy
to radiolabelled 131I-huA33 may result in a treatment that is more effective for the
treatment of colorectal cancer than either agent alone.

The purpose of this study is to determine whether it is safe to give humanised A33 antibody
tagged with radioactive iodine together with chemotherapy. Different dose levels of
radioactive iodine attached to a constant dose of antibody will be given together with a
fixed total daily capecitabine chemotherapy dose. Providing humanised A33 antibody tagged
with radioactive iodine and chemotherapy is tolerated well without major side effects, the
dose of capecitabine chemotherapy given with 131I-huA33 will also be increased in order to
determine the highest dose that can be given safely in combination with radio-labelled
131I-huA33. The effectiveness of the treatment combination against advanced colorectal
cancer will also be assessed.

Patients with advanced colorectal cancer who have never previously received chemotherapy
using capecitabine may be eligible to participate in the study. A total of between 15 and
30 patients are expected to be recruited.

Screening blood tests will be performed to determine eligibility, as well as baseline heart
and lung function tests and appropriate scans to measure tumour size and assess radiation
within the body. Patients will be given a trace labelled (small radiation dose) infusion of
131I-hu A33 into a vein followed a week later by the treatment infusion of 131I-hu A33. The
first infusion will be given as an outpatient but for the second patients will be
hospitalised and confined to a radiation shielded room until radiation levels fall to safe
limits. Oral iodine drops will also be given for 28 days in order to protect the thyroid
gland from the effects of radioactive iodine. Capecitabine chemotherapy will be taken
orally and will commence at the time of the treatment infusion. Each cycle of capecitabine
chemotherapy involves the medication being taken twice per day for a total of 14 days
followed by 7 days rest. A total of 4 cycles of capecitabine will be given after the
treatment infusion.

Blood samples will be taken just before the treatment infusion and then weekly for 9 weeks
and again at 12 weeks. There will be weekly physical examinations until 9 weeks after the
treatment infusion and again at 12 weeks. Total study duration is 13 weeks from the trace
labelled infusion of 131I-hu A33, that is 12 weeks from the treatment infusion of 131I-hu
A33. Patients will only receive one treatment infusion of 131I hu-A33 antibody.

Inclusion Criteria:

- Metastatic colorectal cancer

- Histologically or cytologically proven colorectal cancer

- Measurable disease on CT scan with at least one lesion >/= 2cm diameter (to allow
adequate scout infusion imaging)

- Expected survival of at least 4 months.

- ECOG performance status 0-2.

- Vital laboratory parameters should be within normal range including:

1. Neutrophils >/= 1.5 x 10^9/L;

2. Platelets >/= 150 x 10^9/L;

3. Serum bilirubin
4. calculated creatinine clearance > 50 ml/min

- Age >/= 18 years

- Able and willing to give valid written informed consent

Exclusion Criteria:

- Previous treatment with capecitabine

- Untreated active metastatic disease to the central nervous system (new or enlarging
lesions on CT or MRI), or within 3 months of treatment (ie surgery or radiotherapy)
for brain metastases

- Other serious illnesses, eg, serious infections requiring antibiotics, bleeding

- Liver involvement with metastatic disease > 50% liver volume

- Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry
(6 weeks for nitrosoureas).

- Previous external beam irradiation except if: (i) it was for standard adjuvant pelvic
radiation for rectal cancer; (ii) it was for localised irradiation for skin cancer;
or (iii) the sum total of all previous external beam irradiation port areas is not
greater than 25% of the total red marrow.

- Previous treatment with a monoclonal antibody or antibody fragment AND a positive
huA33 HAHA titre.

- Concomitant treatment with systemic corticosteroids. Topical or inhalational
corticosteroids are permitted

- Mental impairment that may compromise the ability to give informed consent and comply
with the requirements of the study.

- Lack of availability of the patient for clinical and laboratory follow-up assessment.

- Participation in any other clinical trial involving another investigational agent
within 4 weeks prior to enrollment.

- Pregnancy or breastfeeding.

- Women of childbearing potential: Refusal or inability to use effective means of

Type of Study:


Study Design:

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

Outcome Measure:

- Safety and tolerability of 131I-huA33 combined with capecitabine (NCI-CTCAE)

Outcome Time Frame:

13 weeks

Principal Investigator

Prof. Andrew M Scott, MBBS, DDU MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ludwig Institute for Cancer Research


United States: Food and Drug Administration

Study ID:




Start Date:

October 2003

Completion Date:

December 2008

Related Keywords:

  • Colorectal Neoplasms
  • Neoplasms
  • Colorectal Neoplasms