This study is a Pilot clinical trial. Pilot clinical trials test the safety of an
investigational combination of drugs. Pilot studies provide information on what effects, both
good and bad, the Investigational agent might have on your disease. "Investigational" means
that the intervention is still being studied and that research doctors are trying to find out
more about it. It also means that the FDA has not approved the treatment for your type of
cancer.
The main purposes of this study are to determine:
- The amount of vaccine that can be made for your colorectal tumor cells
- If the vaccine can be given safely
- What the effects of the vaccine are, both good and bad
- How the vaccine affects your immune system
- Whether this vaccine might have any effect on the return of your cancer in the liver
after surgical removal
This study is being done because there are currently no treatments which have demonstrated to
cure diseae which has progressed, or moved beyond the site of the primary site of disease
(colon or rectum). These vaccinations will be given after you have completed the standard of
care treatment as determined by your doctor.
Laboratory research has made vaccines from cancer cells by inserting genetic material from a
protein called granulocyte-macrophage colony stimulating factor (GM-CSF) into the cancer
cell. Once complete, the cancer cells are able to produce large amounts of GM-CSF. The
vaccine made form these cells has a greater anti-tumor effect than cancer cells without
GM-CSF. The purpose of this research study is to determine the safety of an investigational
vaccine that will be made using your own colorectal cancer cells in the manner described
above.
This vaccine has been used in several other research studies for treatment for other cancers
(skin, lung, ovarian, sarcoma and leukemia.) Information from these other research studies
suggests that this vaccine may help to reduce the risk of your colorectal cancer returning
after you have your colorectal cancer surgery.
Due to these results in melanoma and several other tumors we are encouraged to use this
vaccine approach in patients with liver metastases from colorectal cancer, after the cancer
in the liver has been removed by surgery.
After you have given your consent to participate in this study, your study doctor will
perform some tests to confirm that you are eligible to participate. These tests may take
place up to 21 days before the surgery to remove a liver tumor, which will be used to create
the vaccines. Many of the following examinations are commonly done to determine diagnosis
and/or stage of disease and you may have already had some or all of these evaluations. They
may or may not have to be repeated. These tests include a medical history, performance
status, blod samples, routine blood tests, tumor assessment and blood pregnancy test (if
applicable). If these tests indicate you are eligible for this study and you agree to
participate, you will be referred to a surgeon for the surgical removal of tumor tissue from
which the vaccine will be made.
The surgery will be performed at Massachusetts General Hospital. You will be asked to sign a
separate consent form to give permission to the surgeon to perform this operation. That
consent will describe the risks of the operation which involves removing the tumor cells from
your liver.
After your surgery, there is a possibility that your physician will recommend other treatment
before starting the vaccines if he or she feels it would be beneficial to your care and
medically appropriate. This part of the treatment would not be experimental (for example,
chemotherapy or radiation therapy).
Then, in this case, the vaccines made from your cancer will not be administered to you until
at least 4 weeks after your last chemotherapy or radiation treatment. If the time between
your operation and the first scheduled vaccine injection is 8 weeks or longer, we will ask
you to undergo another chest, abdomen and pelvic CT scan and clinical blood work to confirm
that it is still safe for you to proceed with the vaccines. After this 4 week rest period,
vaccine administration will occur as previously outlined.
If these tests indicate you are eligible for this study and you agree to participate, you
will be referred to a surgeon for the surgical removal of tumor tissue from which the vaccine
will be made.
It is important to know that sometimes we are unable to collect enough cells from the tumor
collection. In those cases we can try to grow the tumor cells for a short period of time to
get enough cells to make a vaccine, but we can not guarantee that we will always be able to
produce vaccine for every participant who undergoes tumor cell collection.
The vaccines created from your colorectal cancer cells are scheduled to be given to you on
days 1, 8, 15 and then every two weeks after that until 6 total vaccines have been
administered. The amount of vaccines is dependent on the total amount of cells collected when
your colorectal cancer liver metastasis is processed and prepared into vaccine in our lab. It
is hoped that you will receive at least six vaccines. All scheduled treatment will occur in
the outpatient clinic.
The vaccines will be administered in two injections that will be placed underneath your skin.
The two injections will be given at the same place on your body. The recommended sites are
your arms, thighs or trunk area and the sites will rotate per vaccine.
Day 1 is the first day of treatment on study. The following procedures are planned on this
day: update of medical history, physical exam, blood samples for routine labs, required blood
sample for immune studies, vaccine administration, and, if enough cells can be grown, you
will receive an injection of cancer cells that have been killed but not able to secrete
GM-CSF. This is done to measure the amount of reaction of your immune system caused by the
vaccine alone.
Punch biopsies will be obtained 2 days after the first and fifth vaccinations. A DTH
injection will also be administered at the first and fifth vaccine. Two days after the
vaccine and DTH administration punch biopsy will be taken. DTH injections are Delayed-type
Hyper-sensitivity Tests. This injection inserts a small amount of the vaccine under your skin
to determine if you have any allergic reactions to the vaccine. This will consist of a small
piece of skin tissue removed under local anesthesia. A small stitch will be placed after the
biopsy. You will sign a separate consent form for this procedure.
The following procedures are planned for Days 8 and 15: update of medical history, weight and
vital signs, blood samples for routine labs and immune studies, and vaccine administration.
On day 29 and every two weeks (until no more vaccines are available) you wil undergo an
update of medical history, physical exam, weight and vital signs, blood samples for routine
labs and immune studies, punch biopsy and vaccine administration. With vaccine #5, you may
receive a second DTH injection. Two days after the vaccine and DTH injection, punch biopsies
will be taken off both sites to further evaluate your body's response to the treatment.
After the final dose of study drug, your treating physician will determine if you are
eligible to receive a second series of vaccinations. In addition, there must be sufficient
numbers of cells for vaccine remaining from the original harvest or a new liver metastasis
has occurred and been removed to make more vaccine.
If you give consent to participate in the repeat dose phase, you will be required to repeat
the screening tests to see if you are still eligible to participate in the study.
It is possible that additional rounds of vaccine therapy may be offered after the second
round, as long as it is appropriate in the opinion of your treating physician and additional
tumor is available to make vaccine and you continue to meet the eligibility criteria.
Participants will be monitored every 3 months with a blood test for the first 3 years and
then every 6-12 months for a total of 5 years. Staging CT scans will be performed 3 months
after the last vaccination, then every 6 months for the first three years and then yearly to
year 5. After 5 years imaging will be at the discretion of the treating physician. Blood
draws for immune research studies will occur every 3 months for 2 years after completing all
vaccinations.
Inclusion Criteria:
- Histologically documented hepatic colorectal cancer metastasis with resectable hepatic
lesions
- At least 4 weeks since last dose of chemotherapy, radiotherapy, immunotherapy,
systemic glucocorticoid therapy or operation in order to receive vaccine
- Fully recovered from hepatic resection
Exclusion Criteria:
- Pregnant or breastfeeding
- Uncontrolled active infection
- Infection with HIV, Hepatitis B or C
- Other current malignancies except in situ cancer or basal/squamous cell carcinoma
- Active autoimmune disease
- Hepatic metastases involving both branches of the portal vein or all three hepatic
veins
- Peritoneal metastases identified at the time of attempted resection
- Greater than 1 month since resection of liver metastasis for vaccine production
