HER2 Directed Dendritic Cell Vaccine, Trastuzumab, Pertuzumab, and Chemotherapy in Treating Participants with Stage II-III HER-2 Positive Breast Cancer

Status: Active

Description

This early phase I trial studies how well a HER2 directed dendritic cell vaccine, trastuzumab, pertuzumab, and chemotherapy work in treating participants with stage II-III HER-2 positive breast cancer. Dendritic cells are immune cells that can tell the immune system to fight infection. Vaccines made from a person's dendritic cells may help the body build an effective immune response to kill tumor cells that express HER2. Immunotherapy with monoclonal antibodies, such as trastuzumab and pertuzumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as docetaxel and carboplatin, 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. Giving a HER2 directed dendritic cell vaccine, trastuzumab, pertuzumab, and chemotherapy may work better in participants with HER-2 positive breast cancer.

Eligibility Criteria

Inclusion Criteria

  • Patients must have histologically confirmed clinical stage II or III estrogen receptor negative (ER-) progesterone receptor (PR) - HER2 positive (+) (per College of Pathologists [CAP] criteria) invasive carcinoma of the breast
  • Medically and surgically appropriate to undergo neoadjuvant chemotherapy with TCH-P Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), Perjeta (pertuzumab) regimen followed by standard of care local therapy as determined by their treating physician
  • Eastern Cooperative Oncology Group (ECOG) performance status < 2
  • Leukocytes >= 3,000/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Cardiac ejection fraction within institutional normal limits by either multigated acquisition scan (MUGA) or echocardiogram (ECHO) at baseline
  • Women of child-bearing potential and their male partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; sexually active male participants should use a barrier method or exercise abstinence during chemotherapy administration until surgery
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Patients with inflammatory breast cancer, widespread locally advanced unresectable disease involving the chest wall/nodal basins in which a curative surgical resection cannot be performed, or those in whom de novo metastatic disease is suspected or confirmed
  • Patients may not be receiving any other investigational agents for the treatment of their breast cancer
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study vaccine components and any of the chemotherapy drugs (docetaxel, carboplatin, trastuzumab, pertuzumab)
  • Patients who are unwilling or unable to undergo an apheresis for production of their vaccine
  • 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 situations that would limit compliance with study requirements
  • Pregnant women and women who are breastfeeding are excluded from this study
  • Patients with known congenital or acquired immune deficiency (including those patients who require systemic immunosuppressant drugs for autoimmune disease or organ transplant)
  • Patients with pre-existing peripheral neuropathy that would limit treatment with taxanes and platinum agents

Locations & Contacts

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Hatem H. Soliman
Phone: 813-745-4933
Email: Hatem.soliman@moffitt.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Immunogenicity of human epidermal growth factor 2 (HER2) dendritic cell (DC) vaccine by week 4 enzyme-linked immunosorbent spot assay (ELISPOT).

II. Pathologic complete response rate of treated patients.

SECONDARY OBJECTIVES:

I. Safety/toxicity using Common Terminology Criteria for Adverse Events (CTCAE) 4.03 criteria.

II. Recurrence free survival rate at 3 years.

III. Persistence of immune response throughout booster sequence.

OUTLINE: Participants are assigned to 1 of 2 arms.

ARM A: Participants receive a HER2 directed DC vaccine intranodally once a week for 3 weeks. Beginning in week 4, participants then receive docetaxel intravenously (IV), carboplatin IV, and pertuzumab IV once every 3 weeks for up to 6 courses, and trastuzumab IV once every 3 weeks for 52 weeks in the absence of disease progression or unacceptable toxicity. Participants also undergo surgery during weeks 26-28, and receive HER2 directed DC booster vaccines at week 25, 56, 80, and 104.

ARM B: Participants receive a HER2 directed DC vaccine intranodally twice a week, 3 days apart, for 3 weeks. Participants also receive docetaxel, carboplatin, trastuzumab, and pertuzumab, undergo surgery, and receive HER2 directed DC booster vaccines as in Arm A.

After completion of study treatment, participants are followed up at 30 days and every 6 months for up to 3 years.

Trial Phase & Type

Trial Phase

No phase specified

Trial Type

Treatment

Lead Organization

Lead Organization
Moffitt Cancer Center

Principal Investigator
Hatem H. Soliman

Trial IDs

Primary ID MCC-19337
Secondary IDs NCI-2018-00628
Clinicaltrials.gov ID NCT03387553