Concurrent WOKVAC Vaccination, Chemotherapy, and HER2-Targeted Monoclonal Antibody Therapy Before Surgery for the Treatment of Patients With Breast Cancer

Official title

A Phase II Study of Concurrent WOKVAC Vaccination With Neoadjuvant Chemotherapy and HER2-Targeted Monoclonal Antibody Therapy

Overview

This phase II trial studies the immunologic response and side effects of using the WOKVAC vaccine in combination with chemotherapy and HER2-targeted monoclonal antibody therapy before surgery in treating patients with breast cancer. Vaccines like WOKVAC are made from tumor-associated antigens which may help the body build an effective immune response to kill tumor cells. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab and pertuzumab are forms of targeted therapy because they work by attaching themselves to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab and pertuzumab attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving the WOKVAC vaccine at the same time (concurrently) with paclitaxel, trastuzumab, and pertuzumab before surgery may kill more tumor cells.

Detailed description

OUTLINE:

Patients receive WOKVAC intradermally (ID) on day 13. Treatment repeats for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive paclitaxel via infusion on days 1, 8, and 15 or docetaxel intravenously (IV) and carboplatin IV on day 1, and trastuzumab IV and pertuzumab IV on day 1. The chemo and trastuzumab and pertuzumab will most likely be given by the patient's own oncologist per standard of care. Treatment repeats for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ultrasound imaging or magnetic resonance imaging and biopsy on study and blood sample collection throughout the study.

After completion of study treatment, patients are followed up annually for up to 5 years from enrollment.

Interventions

• Biological pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine
  Given ID
• Drug Paclitaxel
  Given via infusion
• Biological Trastuzumab
  Given IV
• Biological Pertuzumab
  Given IV
• Drug Docetaxel
  Given IV
• Drug Carboplatin
  Given IV
• Procedure Ultrasound Imaging
  Undergo ultrasound imaging
• Procedure Biopsy Procedure
  Undergo biopsy
• Procedure Biospecimen Collection
  Undergo blood sample collection

Primary outcome measures

• Enumeration of the number of T-bet+, CD4+, and CD8+ T-cells in tumor infiltrating lymphocytes (TIL) after combination immune-chemotherapy [Time frame: Up to completion of surgical resection]

Secondary outcome measures (2)

• Incidence of adverse events [Time frame: Up to 5 years]
• Induction of type 1 helper cell (Th1) immunity against HER2, IGF-1R, and IGFBP2 [Time frame: Up to day 13 of cycle 4 (each cycle is 21 days)]

Eligibility criteria

Inclusion criteria

• Patients must be at least >= 18 years of age
• Clinical stage I-III breast cancer, HER2+ (per American Society of Clinical Oncology \[ASCO\]/College of American Pathologists \[CAP\] guideline update, 2018), regardless of estrogen receptor (ER)/ progesterone receptor (PR) status and planning to undergo neoadjuvant therapy with either paclitaxel, trastuzumab, and pertuzumab (THP) or docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP)
• Patients who have received prior neoadjuvant chemotherapy are allowed but may only receive paclitaxel, trastuzumab, and pertuzumab for the duration the study
• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• White blood cell (WBC) >= 3000/mm\^3 (within 4 weeks of initiating study treatment)
• Lymphocyte count >= 500/mm\^3 (within 4 weeks of initiating study treatment)
• Absolute neutrophil count (ANC) >= 1,500/ uL (within 4 weeks of initiating study treatment)
• Platelets >= 75,000/ uL (within 4 weeks of initiating study treatment)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be < 3.0 mg/dL (within 4 weeks of initiating study treatment)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal (ULN) (within 4 weeks of initiating study treatment)
• Creatinine =< 2.0 mg/dL or creatinine clearance > 30 ml/min (within 4 weeks of initiating study treatment)
• Left ventricular ejection fraction (LVEF) >= lower limit of normal for institution performing the multi-gated acquisition (MUGA) or echocardiogram (ECHO) done within 3 months of initiating study treatment
• Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last vaccine
• Ability to understand and willingness to sign a written informed consent document

Exclusion criteria

• Patients with any of the following cardiac conditions:

• Symptomatic restrictive cardiomyopathy
• Dilated 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
• Uncontrolled autoimmune disease requiring active systemic treatment
• Known hypersensitivity reaction to the granulocyte-macrophage colony stimulating factor (GM-CSF) adjuvant; any known contra-indication to GM-CSF
• Pregnant or breast feeding
• Known human immunodeficiency virus (HIV)-positive
• History of uncontrolled diabetes
• Known current or a history of hepatitis B or C virus, including chronic and dormant states, unless disease has been treated and confirmed cleared
• Major surgery within the 4 weeks prior to initiation of study vaccine
• Current use of immunosuppressive agents or systemic corticosteroids. Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption) are allowed. Patients who have received systemic corticosteroids =< 30 days prior to starting study drug will be excluded

\* NOTE: Steroids given as supportive care for the neoadjuvant chemotherapy regimens is allowable per standard of care

• Patient is currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug
• Patients may not be receiving any other investigational agents

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Fred Hutch/University of Washington Cancer Consortium — Seattle

Identifiers

NCT: NCT04329065 · RG1005296 · NCI-2020-01662 · W81XWH-16-1-0385 · 10159

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗