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

NCT ID: NCT00880464

Last Updated: 2022-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-01
• Study Completion Date: 2021-06-30

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Autologous, Lethally Irradiated Breast Cancer Cells

Intervention Type: BIOLOGICAL

Vaccination with autologous tumor cells engineered by adenoviral mediated gene transfer to secrete GM-CS

Interventions

Autologous, Lethally Irradiated Breast Cancer Cells

Vaccination with autologous tumor cells engineered by adenoviral mediated gene transfer to secrete GM-CS

Intervention Type: BIOLOGICAL

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Ana C Garrido-Castro

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Beth Overmoyer, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35482127 (View on PubMed)

Other Identifiers

08-216

Identifier Type: -

Identifier Source: org_study_id