A Phase Ib Study of Autologous Vaccination With Lethally Irradiated, Autologous Breast Cancer Cells Engineered by Adenoviral Mediated Gene Transfer to Secrete GM-CSF Following Preoperative Chemotherapy in Women With Operable Breast Cancer
18 Years
N/A
Both
Breast Cancer
Trial Information
A Phase Ib Study of Autologous Vaccination With Lethally Irradiated, Autologous Breast Cancer Cells Engineered by Adenoviral Mediated Gene Transfer to Secrete GM-CSF Following Preoperative Chemotherapy in Women With Operable Breast Cancer
After the patient has given their consent to participate in the trial, a series of tests
will be performed to determine if the patient is eligible. These tests may take place up to
21 days before the surgery to remove a tumor sample or cancer-containing fluid, which will
be used to create the vaccines. The tumor cells or fluid is then brought to a special,
certified laboratory where the vaccine is made. Specially trained laboratory technicians
then use a method known as adenoviral mediated gene transfer, which adds a new gene to the
cancer cells. This gene causes the cells to make GM-CSF, a powerful hormone that stimulates
the immune system. The cells are then given radiation so that they will not grow.
Participants will start receiving vaccine on day 1, 8, 15, 29, and then every two weeks
until the supply of vaccine has run out. The amount of the vaccine depends upon the total
amount of cells that are obtained from the breast cancer tumor or fluid. Each time the
patient is vaccinated, they will be given injections that will be placed underneath the
skin. A different place will be used for each injection. If there are enough cells from the
patient's tumor sample, the patient will be given an injection of non-transduced irradiated
cells (the gene was not added) . These cells will help to measure how the patient's immune
system is reacting to the tumor cells. This is called Delayed-Type Hypersensitivity (DTH).
With vaccine #1 and #5, the patient will also receive a DTH injection. Two to three days
after the vaccine and DTH injection, skin biopsies will be taken of both sites. At week 10
in the study treatment, or earlier if necessary, the patient will have a chest, abdomen, and
pelvic CT scan to determine if the vaccine therapy has had an effect on their disease. A
brain MRI will be performed if there were any abnormalities on the first brain MRI or if new
symptoms have developed. 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 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.
Inclusion Criteria:
- Histologically or cytologically confirmed invasive breast cancer, pre-operative
stages II-III per AJCC 6th edition, based on baseline evaluation by clinical
examination and/or breast imaging
- Cohort 1: At least 2cm of residual disease in sum of diameters by clinical or
radiographic findings following their preoperative chemotherapy
- Cohort 2: Patients who have not received preoperative chemotherapy must have at
least 4cm of disease in the largest diameter by clinical or radiographic findings
- Prior therapy for Cohort 1 only: Must have completed preoperative (neoadjuvant)
chemotherapy with either a standard regimen (containing an anthracycline and/or a
taxane) or on a clinical trial
- HER2 positive tumors must have received at least one prior trastuzumab-based therapy,
and may not receive concurrent trastuzumab therapy and vaccination
- Must initiate hormonal therapy (if indicated), including ovarian suppression, at
least 4 weeks prior to initiation of vaccinations
- Must have completed definitive resection of primary tumor with adequated excision of
gross disease. Surgery should have occured more than 28 days but within 12 weeks
prior to enrollment
- May receive concurrent hormonal therapy, such as tamoxifen, ovarian suppression, and
aromatase inhibitors
- Must have had prior banked tumor of sufficient cellular yield for vaccination
- ECOG Performance Status 0 or 1
- 18 years of age or older
- Greater than 4 weeks from immunotherapy, or systemic glucocorticoid therapy
- Adequate recovery from recent surgery and radiation therapy
Exclusion Criteria:
- Uncontrolled active infection or illness
- Other medical or psychiatric illness or social situation that would limit study
compliance
- Pregnancy or nursing mothers
- Evidence of HIV infection
- Previous participation in an adenovirus-based trial
- Concurrent invasive malignancies
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To determine the doses of lethally irradiated, autologous breast cancer cells engineered by adenoviral mediated gene transfer to secrete GM-CSF that can be manufactured in patients with metastatic breast cancer
Outcome Time Frame:
3 years
Safety Issue:
No
Principal Investigator
Beth Overmoyer, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Dana-Farber Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
08-216
NCT ID:
NCT00880464
Start Date:
April 2009
Completion Date:
April 2015
Related Keywords:
- Breast Cancer
- autologous vaccination
- GM-CSF
- adenoviral mediated gene transfer
- Stage IV breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| Brigham and Women's Hospital | Boston, Massachusetts 02115 |
