Safety and Immune Response to a Mammaglobin-A DNA Vaccine In Breast Cancer Patients Undergoing Neoadjuvant Endocrine Therapy

NCT02204098 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 201407100W81XWH-15-1-0101
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Breast Carcinoma; Malignant Neoplasm of Breast

Outcome Measures

Primary Outcomes (1)

• Safety as measured by the number of participants who experience an adverse event

  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

  Day 126 (+/- 7days)

Secondary Outcomes (3)

• Immune response

  Week 52

• Progression-free survival (PFS)

  5 years

• Overall survival (OS)

  5 years

Other Outcomes (1)

• Objective tumor response rate (ORR)

  5 years

Study Arms (4)

Cohort 1:Neoadjuvant endocrine therapy alone

ACTIVE COMPARATOR

* 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

Procedure: Optional biopsy

Cohort 2:Neoadjuvant endocrine + mammaglobin-A DNA vaccine

EXPERIMENTAL

* 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

Biological: Mammaglobin-A DNA Vaccine; Procedure: Optional biopsy

Cohort 3: Neoadjuvant chemotherapy alone

ACTIVE COMPARATOR

* 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

Procedure: Optional biopsy

Cohort 4: Neoadjuvant chemotherapy + mammoglobin-A DNA vaccine

EXPERIMENTAL

* 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

Biological: Mammaglobin-A DNA Vaccine; Procedure: Optional biopsy

Interventions

Mammaglobin-A DNA Vaccine BIOLOGICAL

Cohort 2:Neoadjuvant endocrine + mammaglobin-A DNA vaccine; Cohort 4: Neoadjuvant chemotherapy + mammoglobin-A DNA vaccine

Optional biopsy PROCEDURE

Cohort 1:Neoadjuvant endocrine therapy alone; Cohort 2:Neoadjuvant endocrine + mammaglobin-A DNA vaccine; Cohort 3: Neoadjuvant chemotherapy alone; Cohort 4: Neoadjuvant chemotherapy + mammoglobin-A DNA vaccine

Eligibility Criteria

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

You may qualify if:

• 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 ≤2.
• 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
• platelets ≥100,000/μL
• total bilirubin ≤institutional upper limit of normal
• AST/ALT ≤2.5 X institutional upper limit of normal
• creatinine ≤ institutional upper limit of normal OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine above IULN
• Postmenopausal or premenopausal. NOTE: Postmenopausal women, verified by: (1) bilateral surgical oophorectomy, or (2) no spontaneous menses ≥ 1 year or (3) no menses for \<1 year with FSH and estradiol levels in postmenopausal range, according to institutional standards. Premenopausal women, verified by: (1) regular menses, or (2) FSH and estradiol levels in premenopausal range, according to institutional standards.
• Able to understand, and willing to sign a written informed consent document.

You may not qualify if:

• Received any of the following for treatment of this cancer (except for the neoadjuvant endocrine therapy or chemotherapy specified within this protocol):
• Surgery
• 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.
• Prior axillary lymph node sampling (sentinel lymph node biopsy or axillary lymph node dissection). FNA or core needle biopsy of axillary lymph node is acceptable.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
• Prior or currently active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication (e.g., corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids is acceptable. Any patients receiving steroids should be discussed with the PI to determine if eligible.
• Pregnant or breastfeeding. A negative serum or pregnancy test is required no more than 7 days before study entry, and patients must be willing to employ adequate contraception. Women of childbearing potential must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Known HIV-positive status. These patients are ineligible because of the potential inability to generate an immune response to vaccines.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Rising Tide Foundation: collaborator
• United States Department of Defense: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• William Gillanders, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2014
• First Posted: July 30, 2014
• Study Start: January 7, 2015
• Primary Completion: April 6, 2022
• Study Completion (Estimated): August 31, 2028
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)