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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Breast Cancer	Biological: Autologous, Lethally Irradiated Breast Cancer Cells	Phase 1; Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	20 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Study Start Date :	April 2009
Estimated Primary Completion Date :	April 2018
Estimated Study Completion Date :	July 2019

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Vaccine; Biological/Vaccine: 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	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

Outcome Measures

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Primary Outcome Measures :

1. 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 ]
2. to determine the safety and biologic activity of this vaccination in metastatic breast cancer patients [ Time Frame: 3 years ]

Secondary Outcome Measures :

1. To monitor the rate of recurrent disease, either local or distant, in this patient population [ Time Frame: 3 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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
• 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

Contacts and Locations

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Locations

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

Sponsors and Collaborators

Dana-Farber Cancer Institute

Brigham and Women's Hospital

Investigators

Principal Investigator:	Beth Overmoyer, MD	Dana-Farber Cancer Institute

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Beth Overmoyer, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00880464 History of Changes
Other Study ID Numbers:	08-216
First Posted:	April 13, 2009
Last Update Posted:	September 20, 2017
Last Verified:	September 2017

Keywords provided by Beth Overmoyer, MD, Dana-Farber Cancer Institute:

autologous vaccination; GM-CSF; adenoviral mediated gene transfer; Stage IV breast cancer

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases	Skin Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs