Trial Information

A Phase II Trial Assessing Autologous, Tumor-Pulsed Dendritic Cells as a Tumor Vaccine Administered With IL-2 in Patients With Metastatic Colorectal Cancer

Pretreatment screening: If a subject decides to participate in this study they will first be
presented the informed consent document to read and review with the Principal Investigator
(or his designee) to go over each aspect of the study and answer any questions. Once the
patient has consented, they will first be screened to make sure they meet the eligibility
criteria. The screening process is done to make sure that it is appropriate for the subject
to participate in this study. This process will include a review of their medical history,
a complete physical examination, standard blood tests, an EKG (an electrocardiogram), a
chest x-ray and if it is possible for them to become pregnant, a pregnancy test. These
tests are normally performed on patients prior to receiving chemotherapy for cancer. In
addition to these tests which are normally performed, blood will be obtained for tests which
are specific for this investigational study.

These study specific tests include a blood test to determine whether a subject may be
infected with the hepatitis B virus or the AIDS virus, and blood tests to determine the
ability of their immune system to respond to normal stimulation. A doctor will also order
CT scans or nuclear medicine scans to measure the extent of the subject's cancer because the
study therapy has a possibility of shrinking the tumor and this will be determined by
measuring each subject's disease before and after therapy.

At the time of this initial evaluation subjects will have skin tests that will determine
their ability to mount an immune response to infectious agents (such as tetanus, measles,
mumps) that they have been exposed to or vaccinated against. If a subject fails to
demonstrate a response to all the skin tests, they will not be allowed to participate in
this study because such lack of response indicates that their immune system may not respond
to the therapy planned in this study.

Vaccine therapy: In order to make a vaccine from a subject's tumor they must have surgical
removal of some tumor in order to provide tumor cells. The doctor will determine if a
subject has colorectal cancer cells that are easily obtainable. However, if a subject
already has an available frozen tumor specimen at the University of Michigan, that may be
used for the vaccine preparation instead of undergoing another surgical procedure. This
surgery may be done solely for the purpose of participating in this research and may not
otherwise benefit a subject. A separate consent form will be required for any surgery a
subject undergoes.

The cancer cells obtained from each subject will be taken to the laboratory where they will
be separated into single cells, disrupted to make cell fragments, radiated to kill the cells
and then mixed with your dendritic cells. The dendritic cells will be obtained from the
peripheral blood. Subjects will undergo a procedure called leukapheresis that involves
placing a large needle (central line) in a vein in each of their arms. These central lines
will be inserted under local anesthesia (subjects will remain awake…only the site of the
insertion will be “frozen”). Blood exits from one needle and is processed through a machine
that selectively removes one kind of white blood cell and then returns the other elements of
the blood back to their body. The leukapheresis procedure generally lasts three to four
hours. Following the procedure, the dendritic cells will be cultured in the laboratory to
increase the number of dendritic cells. This procedure takes about 2 days.

The tumor-exposed dendritic cell vaccine will be administered as an intradermal (into the
skin) injection into a subject's thigh or arm on days 1, 15 and 29 of study treatment.
Additionally, they will receive IL-2 by subcutaneous injection daily for 4 days after each
vaccination.

Four weeks after their last vaccination, subjects will undergo skin testing to determine if
they are reactive to their tumor cells. White blood cells will also be obtained by a second
leukapheresis procedure to determine, via research tests in the laboratory, if their
circulating immune cells have developed the capacity to respond to their cancer cells. This
skin testing and leukapheresis are for research purposes.

Also, 4 weeks after subjects receive their last vaccination, they will have x-rays and/or
CT scans done to determine whether their disease has responded to the immune therapy. If
their cancer has not worsened or if it has shrunk, then they will be offered the option to
receive additional vaccinations using the tumor-pulsed dendritic cells providing that they
did not experience severe toxicity with the first series of vaccinations and provided there
is enough vaccine material available. The additional vaccinations would be done using the
same procedure and schedule as the previous vaccinations until there is evidence that the
subject's disease has started to grow or worsen. This includes leukapheresis, vaccination,
and IL-2 administration. Re-treatments will be offered until a subject's disease gets worse
or tumor cells are no longer available to produce vaccines. A subject's study participation
will end with the leukopheresis and tumor evaluation 4 weeks following their last series of
vaccinations.

Blood Drawing: The maximum amount of blood, for standard tests and research purposes that
will be drawn during the 10 weeks will be a total of 100ccs, which is approximately 20
teaspoons, which is equivalent to approximately 7 tablespoons over the 12 week time period.

The length of time a subject would be on this study is a minimum of nine weeks. If the
physician determines that a subject is benefiting from this study, they may continue repeat
vaccinations for as long as they continue to have clinical benefit from the study and
vaccine is available. During the study, if other therapy alternatives become clinically
indicated, they will be discussed with the subject. Also, if there are any significant new
findings developed over the course of this research which may affect a subject's willingness
to participate, they will be told of them.