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

NCT00880464 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 08-216
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

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

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 58 Months

Secondary Outcomes (1)

• Median Follow-up Time by Survival Status

  Up to 14 Years

Study Arms (1)

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.

Biological: Autologous, Lethally Irradiated Breast Cancer Cells

Interventions

Autologous, Lethally Irradiated Breast Cancer Cells BIOLOGICAL

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

Vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• years of age or older
• Greater than 4 weeks from immunotherapy, or systemic glucocorticoid therapy
• Adequate recovery from recent surgery and radiation therapy

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 35482127 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Beth Overmoyer
• Organization: Mass General Brigham

Beth_Overmoyer@DFCI.HARVARD.EDU

617 632 3800

Study Officials

• Beth Overmoyer, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 10, 2009
• First Posted: April 13, 2009
• Study Start: January 1, 2006
• Primary Completion: October 1, 2011
• Study Completion: June 1, 2021
• Last Updated: April 1, 2022
• Results First Posted: November 9, 2021

Record last verified: 2022-03

Locations

US (2)