Breast CancerPhase 1NCT00880464
Autologous Vaccination With Lethally Irradiated, Autologous Breast Cancer Cells Engineered to Secrete GM-CSF in Women With Operable Breast Cancer
A Phase 1 study testing Autologous, Lethally Irradiated Breast Cancer Cells in people with Breast Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Autologous, Lethally Irradiated Breast Cancer Cells
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2006to Jun 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this 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
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
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Autologous, Lethally Irradiated Breast Cancer Cells
- Keywords
- autologous vaccination, GM-CSF, adenoviral mediated gene transfer, Stage IV breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous, Lethally Irradiated Breast Cancer CellsBiological
Vaccination with autologous tumor cells engineered by adenoviral mediated gene transfer to secrete GM-CS
| Study group | Role | What they receive |
|---|---|---|
| Vaccine | Experimental | 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. Receives: Biological: Autologous, Lethally Irradiated Breast Cancer Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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. For stage II-III patients, the minimal dose was 1 x 10^5 cells and the maximal dose was 4 x 10^6 cells. For metastatic patients, the minimal dose was 1 x 10^5 cells and the maximal dose was 1 x 10^7 cells.
Measured: 40 Months
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.
Measured: Up to 58 Months
Secondary outcomes (1)
Median Follow-up Time by Survival Status
Participants followed for survival status. Participants who were alive were noted as such as late as December 2020.
Measured: Up to 14 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2009 (estimated)
- Study start1 Jan 2006
- Primary completionOct 2011
- Study completionJun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital
- Responsible party
- Principal investigator, Ana C Garrido-Castro, Dana-Farber Cancer Institute
- Investigators
- Beth Overmoyer, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00880464
- Sponsor's protocol ID
- 08-216
- Status last verified
- Mar 2022
- First submitted
- 10 Apr 2009
- Last updated
- 1 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Anderson KS, Erick TK, Chen M, Daley H, Campbell M, Colson Y, Mihm M, Zakka LR, Hopper M, Barry W, Winer EP, Dranoff G, Overmoyer B. The feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II-III and metastatic breast cancers. Breast Cancer Res Treat. 2022 Jul;194(1):65-78. doi: 10.1007/s10549-022-06562-y. Epub 2022 Apr 28.
PubMed 35482127
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00880464
- Acronym / sponsor ID
- 08-216
- Conditions
- Breast Cancer
- Keywords
- autologous vaccination, GM-CSF, adenoviral mediated gene transfer, Stage IV breast cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital
- Study start
- 1 Jan 2006 (actual)
- Primary completion
- Oct 2011 (actual)
- Study completion
- Jun 2021 (actual)
- First posted
- 13 Apr 2009 (estimated)
- Results
- Posted 9 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vaccine | Experimental | Biological: Autologous, Lethally Irradiated Breast Cancer CellsVaccinations 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous, Lethally Irradiated Breast Cancer CellsVaccination with autologous tumor cells engineered by adenoviral mediated gene transfer to secrete GM-CS | Biological | Vaccine |
Primary outcome
Minimum Number of Vaccine Doses Created Using Participant Tumor Sample
Time frame: 40 Months
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. For stage II-III patients, the minimal dose was 1 x 10^5 cells and the maximal dose was 4 x 10^6 cells. For metastatic patients, the minimal dose was 1 x 10^5 cells and the maximal dose was 1 x 10^7 cells.
Number of Participants With Grade 3 or Higher Adverse Events
Time frame: 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.
1 secondary outcome
Median Follow-up Time by Survival Status
Time frame: Up to 14 Years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35482127Anderson KS, Erick TK, Chen M, Daley H, Campbell M, Colson Y, Mihm M, Zakka LR, Hopper M, Barry W, Winer EP, Dranoff G, Overmoyer B. The feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II-III and metastatic breast cancers. Breast Cancer Res Treat. 2022 Jul;194(1):65-78. doi: 10.1007/s10549-022-06562-y. Epub 2022 Apr 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Beth Overmoyer, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous, Lethally Irradiated Breast Cancer Cells in people with Breast Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Minimum Number of Vaccine Doses Created Using Participant Tumor Sample (time frame: 40 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00880464, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2022.