A Phase I Trial of Vaccination With Autologous, Lethally Irradiated Tumor Cells Engineered by Adenoviral Mediated Gene Transfer to Secrete Granulocyte-Macrophage Colony Stimulating Factor in Pediatric and Adult Patients
The patient will have surgery to remove a portion of the tumor. This tumor is then brought
to a special, certified laboratory where it is broken up into single cells and then washed.
Specially trained laboratory technicians then use a method known as adenoviral mediated gene
transfer, which adds a new gene to the cancer calls. This gene causes the cells to make
GM-CSF, a powerful hormone that stimulates the immune system. The cells are then given
enough radiation so that they will never grow, but not enough to completely destroy them,
developing a vaccine.
The patient is then injected with the vaccine on days 0, 7, 14, 28, and then every two weeks
until the supply of vaccine has run out. The amount of vaccine that can be made depends upon
the total amount of cells taken from the tumor. The actual injections are like childhood
vaccinations that go under the skin or into muscle and a different place will be used for
It is hoped that the cancer cells that have been made to secrete the hormone GM-CSF will
cause the patient's immune system to attack the cancer in other parts of the body.
If the tumor yields enough cells, the patient will also be given an injection of
non-transduced irradiated tumor cells. Non-transduced means that the gene for GM-CSF has
not been added to these cells as it has for the vaccines. This is done to measure the
amount of reaction of the immune system caused by the vaccine. This injection is measuring
delayed type hypersensitivity, or DTH.
The patient will be asked to undergo optional skin biopsies of the vaccine and DTH sites to
see if an immune reaction is occuring at the injection sites 2 days after vaccine 1 and
The following tests and procedures will be performed through out the study: physical exam,
blood samples, immune studies, vital signs and physical exam.
At week 10 in the patient's treatment, or earlier if the doctor feels it is necessary, the
patient will undergo a chest, abdomen and pelvic XT scan. A brain MRI will be performed if
there were any abnormalities on the first brain MRI or if any new central nervous system
symptoms have developed.
If the patient's disease has not disappeared or if new lesions have been found after the
patient receives at least six vaccines, they may have the opportunity to undergo a second
course of study treatment.
Patients may participate in this study until one of the following happens: All vaccine
created from the tumor has been given to the patient; the patient's disease worsens; the
patient experiences an unacceptable and/or harmful side effect; the patient becomes
pregnant; the patient is unable to follow the study plan; or the patient's doctor feels it
is no longer in the best interest of the patient to continue.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the safety and feasibility of preparation and administration of vaccine in patients with metastatic or locally advanced clear cell sarcoma (CCS), alveolar soft part sarcoma (ASPS) and translocation associated renal cell carcinoma (RCC)
F. Stephen Hodi, MD
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Children's Hospital Boston||Boston, Massachusetts 02115|