A Phase 1B Clinical Trial to Evaluate the Safety and Immune Response to a Mammaglobin-A DNA Vaccine in ER+, HER2- Breast Cancer Patients Undergoing Neoadjuvant Endocrine Therapy or Chemotherapy
Overview
- Phase
- Phase 1
- Intervention
- Optional biopsy
- Conditions
- Breast Cancer
- Sponsor
- Washington University School of Medicine
- Enrollment
- 27
- Locations
- 2
- Primary Endpoint
- Safety as measured by the number of participants who experience an adverse event
- Status
- Active, not recruiting
- Last Updated
- 11 days ago
Overview
Brief Summary
The purpose of this research study is to find out about the safety of injecting the gene (DNA) for mammaglobin-A into people with breast cancer. The DNA used in this study was purified from bacteria and contains the gene for mammaglobin-A. Mammaglobin-A is a protein that is highly expressed by breast cancer cells. Injection of mammaglobin-A DNA may be a way to generate an immune response to breast cancer cells. There is evidence that an immune response may be a way to fight cancer. In addition to evaluating the safety of the mammaglobin-A injection, this study is also looking at the immune response that the participant's body has after each injection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A patient will be eligible for inclusion in this study only if ALL of the following criteria apply:
- •Newly diagnosed histologically confirmed invasive breast cancer.
- •Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2- (0 or 1+ by IHC or FISH negative for amplification) breast cancer by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Patients with T1c tumors are eligible if they are considered candidates for neoadjuvant endocrine therapy or chemotherapy
- •At least 1 measurable lesion.
- •Candidate for neoadjuvant endocrine therapy or chemotherapy.
- •At least 18 years of age.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Adequate organ and marrow function no more than 28 days prior to the start of neoadjuvant endocrine therapy or chemotherapy as defined below:
- •WBC ≥3,000/μL
- •absolute neutrophil count ≥1,500/μL
Exclusion Criteria
- •A patient will be ineligible for inclusion in this study if ANY of the following criteria apply:
- •Received any of the following for treatment of this cancer (except for the neoadjuvant endocrine therapy or chemotherapy specified within this protocol):
- •Radiation therapy
- •Chemotherapy
- •Biotherapy
- •Hormonal therapy
- •Investigational agent Note that subjects who do not respond initially to endocrine therapy may receive chemotherapy and remain on study.
- •Receiving any other investigational agent(s) or has received an investigational agent within the last 30 days.
- •Known metastatic disease.
- •Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
Arms & Interventions
Cohort 3: Neoadjuvant chemotherapy alone
* Will be treated with standard of care neoadjuvant chemotherapy as determined by their treating physician * If archival tissue not sufficient, a research biopsy to obtain primary tissue must be done prior to day 28 * Subjects who begin neoadjuvant endocrine therapy but are determined to not be responding at the Day 14 biopsy may begin chemotherapy treatment, at the discretion of the treating physician. These subjects may be enrolled in cohort 3
Intervention: Optional biopsy
Cohort 4: Neoadjuvant chemotherapy + mammoglobin-A DNA vaccine
* Will be treated with standard of care neoadjuvant chemotherapy as determined by their treating physician * If archival tissue not sufficient, a research biopsy to obtain primary tissue must be done prior to day 28 * Treated with 4 mg of mammaglobin-A DNA vaccine at 3 time points (Days 28, 56, and 84) * All study injections will be administered using a TriGrid electroporation device * Subjects who begin neoadjuvant endocrine therapy but are determined to not be responding at the Day 14 biopsy may begin chemotherapy treatment, at the discretion of the treating physician. These subjects may be enrolled in either cohort 4
Intervention: Optional biopsy
Cohort 2:Neoadjuvant endocrine + mammaglobin-A DNA vaccine
* Will be treated with standard of care adjuvant endocrine therapy * Optional biopsy approximately 14 days following initiation of neoadjuvant therapy * Treated with 4 mg of mammaglobin-A DNA vaccine at 3 time points (Days 28, 56, and 84) * All study injections will be administered using a TriGrid electroporation device
Intervention: Optional biopsy
Cohort 4: Neoadjuvant chemotherapy + mammoglobin-A DNA vaccine
* Will be treated with standard of care neoadjuvant chemotherapy as determined by their treating physician * If archival tissue not sufficient, a research biopsy to obtain primary tissue must be done prior to day 28 * Treated with 4 mg of mammaglobin-A DNA vaccine at 3 time points (Days 28, 56, and 84) * All study injections will be administered using a TriGrid electroporation device * Subjects who begin neoadjuvant endocrine therapy but are determined to not be responding at the Day 14 biopsy may begin chemotherapy treatment, at the discretion of the treating physician. These subjects may be enrolled in either cohort 4
Intervention: Mammaglobin-A DNA Vaccine
Cohort 2:Neoadjuvant endocrine + mammaglobin-A DNA vaccine
* Will be treated with standard of care adjuvant endocrine therapy * Optional biopsy approximately 14 days following initiation of neoadjuvant therapy * Treated with 4 mg of mammaglobin-A DNA vaccine at 3 time points (Days 28, 56, and 84) * All study injections will be administered using a TriGrid electroporation device
Intervention: Mammaglobin-A DNA Vaccine
Cohort 1:Neoadjuvant endocrine therapy alone
* Will be treated with standard of care adjuvant endocrine therapy as determined by their treating physician * Optional biopsy approximately 14 days following initiation of neoadjuvant therapy
Intervention: Optional biopsy
Outcomes
Primary Outcomes
Safety as measured by the number of participants who experience an adverse event
Time Frame: Day 126 (+/- 7days)
Assessment of plasmid DNA safety will include both clinical observation and laboratory evaluation. Safety will be closely monitored after injection with eight or more clinical and laboratory assessments in the first 24 weeks of the trial. The following parameters will be assessed following vaccination: 1. Local signs and symptoms 2. Systemic signs and symptoms 3. Laboratory evaluations, including blood counts and serum chemistries 4. Adverse and serious adverse events Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0
Secondary Outcomes
- Immune response(Week 52)
- Progression-free survival (PFS)(5 years)
- Overall survival (OS)(5 years)