Autologous Vaccination With Lethally Irradiated, Autologous Breast Cancer Cells Engineered to Secrete GM-CSF in Women With Operable Breast Cancer

Autologous Vaccination With Lethally Irradiated, Autologous Breast Cancer Cells Engineered to Secrete GM-CSF in Women With Operable Breast Cancer

This study is currently recruiting participants.
Verified by Dana-Farber Cancer Institute, October 2009
First Received: April 10, 2009 Last Updated: October 30, 2009 History of Changes
Sponsor: Dana-Farber Cancer Institute
Collaborator: Brigham and Women's Hospital

Information provided by: Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00880464

Purpose
The purpose of this trial is to test the safety of a vaccine made from a patient's own breast cancer cells, and determine if this vaccine will delay or stop the growth of the cancer. The vaccine is made by genetically modifying a patient's own tumor cells to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) to activate the immune response

Condition Intervention Phase
Breast Cancer
Biological: Autologous, Lethally Irradiated Breast Cancer Cells
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: 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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Granulocyte-macrophage colony-stimulating factor Sargramostim
U.S. FDA Resources

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
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 [ Time Frame: 3 years ] [ Designated as safety issue: No ]

to determine the safety and biologic activity of this vaccination in metastatic breast cancer patients [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
To monitor the rate of recurrent disease, either local or distant, in this patient population [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: April 2009
Estimated Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)

Intervention Details:
Biological: Autologous, Lethally Irradiated Breast Cancer Cells
Vaccine will be administered on days 1, 8, 15, 29 and then every 2 weeks until the supply of vaccine runs out
Detailed Description:
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.

Eligibility

Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Criteria
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
At least 2cm of residual disease in sum of diameters by clinical or radiographic findings following their preoperative chemotherapy
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
Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00880464

Contacts
Contact: Karen S. Anderson, MD, PhD 617-632-5931

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Investigators
Principal Investigator: Karen S. Anderson, MD, PhD Dana-Farber Cancer Institute

More Information

No publications provided

Responsible Party: Dana-Farber Cancer Institute ( Karen Anderson, MD, PhD )
Study ID Numbers: 08-216
Study First Received: April 10, 2009
Last Updated: October 30, 2009
ClinicalTrials.gov Identifier: NCT00880464 History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
autologous vaccination
GM-CSF
adenoviral mediated gene transfer
Stage IV breast cancer

Additional relevant MeSH terms:
Neoplasms by Site
Skin Diseases
Neoplasms
Breast Neoplasms
Breast Diseases