Breast Cancer
Conditions
Keywords
autologous vaccination, GM-CSF, adenoviral mediated gene transfer, Stage IV breast cancer
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.
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.
Interventions
Vaccine will be administered on days 1, 8, 15, 29 and then every 2 weeks until the supply of vaccine runs out
Sponsors
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed Stage IV breast cancer * Prior banked malignant effusion or significant malignant effusion for tumor harvest or surgically-accessible tumor nodule of at least 2cm in greatest diameter by physical exam, magnetic resonance imaging (MRI) or computed tomography (CT) scan * Must have received at least one prior regimen of chemotherapy for metastatic disease * Patients with HER2 positive tumors must have received at least one prior trastuzumab-based therapy in the metastatic setting, and may not receive trastuzumab therapy and vaccine treatment concurrently * Patients may receive concurrent bisphosphonate therapy and/or erythropoetin therapy at any point while on study * ECOG performance status 0 or 1 * Estimated life expectancy of greater than or equal to 6 months * 18 years of age or older * Greater than 4 weeks from immunotherapy, or systemic glucocorticoid therapy * Adequate recovery from drug-related toxicities from prior systemic therapies * Adequate recovery from recent surgery and radiation therapy * Greater than 6 months since bone marrow or peripheral blood stem cell transplant
Exclusion criteria
* Urgent need for cytotoxic chemotherapy, radiotherapy, or surgery in the next 60 days * Uncontrolled active infection or illness * Psychiatric illness/social situation that would limit study compliance * Pregnant or nursing mothers * Evidence of HIV infection * Previous participation in an adenovirus-based trial * Concurrent invasive malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Number of Vaccine Doses Created Using Participant Tumor Sample | Vaccine doses created and banked soon after registration, up to 8 days. | Tumor samples were obtained via malignant effusion or a surgically accessible tumor nodule of 2 cm in greatest diameter. Tumor cells were processed to single cell suspension and transduced with adenoviral vector encoding human Granulocyte-macrophage colony-stimulating factor (GM-CSF). Then, the cells washed extensively and irradiated with 10,000 cGy. Over the next 14 days, sterility cultures were tested for endotoxin and mycoplasma contamination. Individual vaccine cell dose and number varied depending on the final cell yield from vaccine production. The minimal dose was 1 x 10\^5 cells and the maximal dose was 1 x 10\^7 cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3 or Higher Adverse Events | Up to 58 Months | Number of participants with grade 3 or higher adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. |
| Number of Participants With RECIST Criteria Responses | Up to 14 Years | Clinical outcomes as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. For target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria. |
Countries
United States
Participant flow
Recruitment details
January 2006 through May 2008
Participants by arm
| Arm | Count |
|---|---|
| Vaccine Vaccinations will be administered on days 1,8,15 and every two weeks thereafter until the supply of vaccine has been exhausted or the patient is removed from study. As indicated in 5.2.5, vaccine cell dosage will be approximately 1x10 7 , 4x10 6 ,
1x10 6 , or 1x10 5 depending on the final cell yield.
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 | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressive Disease | 3 |
Baseline characteristics
| Characteristic | Vaccine |
|---|---|
| Age, Continuous | 51.5 years |
| Hormone Receptor Status Negative | 4 Participants |
| Hormone Receptor Status Positive | 8 Participants |
| Human Epidermal Growth Factor Receptor 2 Status Negative | 7 Participants |
| Human Epidermal Growth Factor Receptor 2 Status Positive | 5 Participants |
| Median Duration of Stage IV Breast Cancer | 3.45 years |
| Median number of prior lines of chemotherapy in the metastatic setting (range) | 2.5 therapies |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 0 Participants |
| Site of Disease Ascites | 1 Participants |
| Site of Disease Bone | 9 Participants |
| Site of Disease Central Nervous System | 1 Participants |
| Site of Disease Chest Wall | 1 Participants |
| Site of Disease Pleura | 8 Participants |
| Site of Disease Skin / Lymph Nodes | 9 Participants |
| Site of Disease Viscera | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 3 / 12 |
Outcome results
Primary
Minimum Number of Vaccine Doses Created Using Participant Tumor Sample
Tumor samples were obtained via malignant effusion or a surgically accessible tumor nodule of 2 cm in greatest diameter. Tumor cells were processed to single cell suspension and transduced with adenoviral vector encoding human Granulocyte-macrophage colony-stimulating factor (GM-CSF). Then, the cells washed extensively and irradiated with 10,000 cGy. Over the next 14 days, sterility cultures were tested for endotoxin and mycoplasma contamination. Individual vaccine cell dose and number varied depending on the final cell yield from vaccine production. The minimal dose was 1 x 10\^5 cells and the maximal dose was 1 x 10\^7 cells.
Time frame: Vaccine doses created and banked soon after registration, up to 8 days.
Population: Vaccinations prepared for enrolled for vaccine administration population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaccine | Minimum Number of Vaccine Doses Created Using Participant Tumor Sample | 6 doses |
Secondary
Number of Participants With Grade 3 or Higher Adverse Events
Number of participants with grade 3 or higher adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time frame: Up to 58 Months
Population: Analysis population for adverse events is Treated population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vaccine | Number of Participants With Grade 3 or Higher Adverse Events | Grade 3 | 0 Participants |
| Vaccine | Number of Participants With Grade 3 or Higher Adverse Events | Grade 4 | 0 Participants |
| Vaccine | Number of Participants With Grade 3 or Higher Adverse Events | Grade 5 | 0 Participants |
Secondary
Number of Participants With RECIST Criteria Responses
Clinical outcomes as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. For target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria.
Time frame: Up to 14 Years
Population: Clinical outcomes assessed for the treated population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vaccine | Number of Participants With RECIST Criteria Responses | Progressive Disease within 2 months | 8 Participants |
| Vaccine | Number of Participants With RECIST Criteria Responses | Stable Disease with progression at 4 months | 2 Participants |
| Vaccine | Number of Participants With RECIST Criteria Responses | Stable Disease with progression at 13 months | 1 Participants |
| Vaccine | Number of Participants With RECIST Criteria Responses | No Evidence of Disease > 12 years | 1 Participants |