Clinical trial NCT02157051: Vaccine Therapy in Treating Patients With HER2-Negative Stage III-IV Breast Cancer
Official title: A Phase I Trial of the Safety and Immunogenicity of a Multiple Antigen Vaccine (STEMVAC) in HER2 Negative Advanced Stage Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: HER2 Negative Breast Carcinoma
Recurrent Breast Carcinoma
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Stage III Breast Cancer
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Breast Cancer Alliance
First posted: 2014-06-05
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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: OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 4 arms.

Arm 1: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) as 1 injection intradermally (ID) every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

ARM 2: Patients receive CD105/Yb-1/SOX2/CDH3/M2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

ARM 3: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 3 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

ARM 4: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 1 additional STEMVAC vaccine at 3 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

After completion of study treatment, patients are followed up twice yearly for up to 5 years.

Eligibility criteria: 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 (within 30 days of first vaccination)
* Lymphocyte count \>= 800/mm\^3 (within 30 days of first vaccination)
* Platelet count \>= 75,000/mm\^3 (within 30 days of first vaccination)
* Hemoglobin (Hgb) \>= 10 g/dl (within 30 days of first vaccination)
* Serum creatinine \<= 1.2 mg/dl or creatinine clearance \> 60 ml/min (within 30 days of first vaccination)
* Total bilirubin \<= 1.5 mg/dl (within 30 days of first vaccination)
* Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) \<= 2 times upper limit of normal (ULN) (within 30 days of first vaccination)
* Blood glucose \< 1.5 ULN (within 30 days of first vaccination)
* 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

Primary outcomes:
measure: Incidence of toxicity per Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 4.0
timeFrame: Up to 1 month after last vaccine
measure: Immunologic efficacy defined as achievement of a statistically significant increase in Th1 cell immunity for at least 50% of the immunizing antigens as compared to baseline
timeFrame: Up to 5 years
Secondary outcomes:
measure: Memory Th1 dominant immune response to all five antigens over time
timeFrame: Up to 12 months
measure: Modulation of T-regulatory (Treg) cells with vaccination
timeFrame: Up to 12 months
measure: Modulation of MDSC with vaccination
timeFrame: Up to 12 months
measure: STEMVAC specific Type 1 immune response
timeFrame: Up to 12 months
measure: Bac-TA cross-reactive T-cells
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Mary Disis
role: PRINCIPAL_INVESTIGATOR
References: