Patient case: 78-year-old female with sarcoma; genetic feature: MDM2

Clinical trial: Vaccine Therapy in Treating Patients With HER2-Negative Stage III-IV Breast Cancer

Summary: This phase I trial studies the side effects and best dose of multiantigen deoxyribonucleic acid (DNA) plasmid-based vaccine in treating patients with human epidermal growth factor receptor 2 (HER2)-negative stage III-IV breast cancer. Multiantigen DNA plasmid-based vaccine may target immunogenic proteins expressed in breast cancer stem cells which are the component of breast cancer that is resistant to chemotherapy and has the ability to spread. Vaccines made from DNA may help the body build an effective immune response to kill tumor cells.

Detailed description: PRIMARY OBJECTIVES:
  I. To determine the safety of intradermal administration of up to 3 escalating doses of STEMVAC (CD105/Yb-1/SOX2 CDH3/MDM2-polyepitope plasmid DNA vaccine) in patients with HER2-negative advanced stage breast cancer.
  II. To determine the most immunogenic dose of STEMVAC in patients with HER2-negative advanced stage breast cancer.
  SECONDARY OBJECTIVES:
  I. To determine whether a STEMVAC T helper 1 cells (Th1) polyepitope plasmid based vaccine elicits a persistent memory T cell response and whether immunity can be further enhanced/maintained by two additional STEMVAC vaccines (boosters) given 3 and 9 months after the priming regimen.
  II. To evaluate whether STEMVAC vaccination modulates T regulatory cells and myeloid-derived suppressor cells (MDSC).
  OUTLINE: This is a dose-escalation study.
  Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) intradermally (ID) every 28 days for 3 months and booster vaccines at 6 and 12 months in the absence of disease progression or unacceptable toxicity.
  After completion of study treatment, patients are followed up twice yearly for 5 years.

Eligibility: Inclusion Criteria:
  -  Patients with stage III-IV HER2 negative breast cancer treated with primary or salvage therapy and now have:
  -  No evidence of disease (NED), or
  -  Stable bone only disease
  -  Patients who have completed standard of care and recovered with mild to no residual toxicity from recent therapy
  -  Patients must be at least 28 days post cytotoxic chemotherapy, and/or monoclonal antibody therapy (excluding bone-directed therapy), prior to enrollment
  -  Patients must be at least 28 days post systemic steroids prior to enrollment
  -  Patients on bisphosphonates, denosumab, and/or endocrine therapy are eligible
  -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score of =< 1
  -  Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment
  -  Estimated life expectancy of more than 6 months
  -  White blood cells (WBC) >= 3000/mm^3
  -  Lymphocyte count >= 800/mm^3
  -  Platelet count >= 75000/mm^3
  -  Hemoglobin (Hgb) >= 10 g/dl
  -  Serum creatinine =< 1.2 mg/dl when adjusted for body surface area (BSA) or creatinine clearance > 60 ml/min
  -  Total bilirubin =< 1.5 mg/dl
  -  Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 2 times upper limit of normal (ULN)
  -  Blood glucose < 1.5 ULN
  -  All patients who are having sex that can lead to pregnancy must agree to contraception for the duration of study
  Exclusion Criteria:
  -  Patients with any of the following cardiac conditions:
  -  Symptomatic restrictive cardiomyopathy
  -  Unstable angina within 4 months prior to enrollment
  -  New York Heart Association functional class III-IV heart failure on active treatment
  -  Symptomatic pericardial effusion
  -  Patients at risk for gastrointestinal bleeding (example: peptic ulcer disease, prolonged daily non-steroidal anti-inflammatory use)
  -  Patients with any seizure disorder
  -  Patients with any contraindication to receiving rhuGM-CSF based products
  -  Patients with any clinically significant autoimmune disease uncontrolled with treatment
  -  Patients who are simultaneously enrolled in any other treatment study
  -  Patients who are pregnant or breastfeeding

Relevance to patient case: not relevant