Clinical trial NCT00194714: Vaccine Therapy in Treating Patients With Stage IV HLA-A2 and HER2 Positive Breast or Ovarian Cancer Receiving Trastuzumab
Official title: Phase I/II Study of Combination Immunotherapy for the Generation of HER-2/Neu (HER2) Specific Cytotoxic T Cells (CTL) in Vivo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HER2/Neu Positive
HLA-A2 Positive Cells Present
Stage IV Breast Cancer
Stage IV Ovarian Cancer
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-09-19
Enrollment: 22
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I/II trial studies the side effects of vaccine therapy and to see how well it works in treating patients with stage IV major histocompatibility complex, class I, A2 antigen (HLA-A2) and human epidermal growth factor receptor 2 (HER2) positive breast or ovarian cancer who are receiving trastuzumab. Giving booster vaccines made from HER2 peptides may help increase HER2 specific immunity and immune memory cells.

Detailed description: PRIMARY OBJECTIVES:

I. To evaluate the safety of administering a HER2 cytotoxic T-cell (CTL) peptide-based vaccine (HER-2/neu peptide vaccine) to stage IV breast and ovarian cancer patients receiving maintenance trastuzumab.

II. To quantify and characterize antigen specific T cell subsets specific to HER2 in peripheral blood mononuclear cell (PBMC) of patients after vaccination with a HER2 CTL peptide-based vaccine while receiving maintenance trastuzumab.

SECONDARY OBJECTIVES:

I. To evaluate overall survival (OS) in patients who complete a vaccination series with a HER2 CTL peptide-based vaccine while receiving maintenance trastuzumab.

OUTLINE:

Patients receive HER-2/neu peptide vaccine intradermally (ID) once per month for 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months, and then yearly for up to 5 years.

Eligibility criteria: Inclusion Criteria:

* Subjects must have either stage IV breast or ovarian cancer in remission or with stable disease on trastuzumab monotherapy
* HER2 overexpression by immunohistocytochemistry (IHC) of 2+ or 3+, in the primary tumor or metastasis; if overexpression is 2+ by IHC, then patients must have HER2 gene amplification documented by fluorescence in situ hybridization (FISH)
* Subjects must be HLA-A2 positive
* Eligible subjects must have completed appropriate treatment for their primary disease and be off cytotoxic chemotherapy and any immunosuppressive agents such as systemic steroids for at least 30 days prior to enrollment; patients should continue trastuzumab monotherapy throughout the course of this protocol; concurrent hormonal and biphosphonate therapies are allowed
* Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score = 0 or 1
* Male subjects must agree to contraceptive use during the study period (7 months) and non-menopausal female subjects must agree to contraception for the remainder of their childbearing years
* Hematocrit \>= 30 performed within 60 days of enrollment
* Platelet count \>= 100,000 performed within 60 days of enrollment
* White blood cells (WBC) \>= 3000/ul performed within 60 days of enrollment
* Stable creatinine =\< 2.0 mg/dL or creatinine clearance \>= 60 ml/min performed within 60 days of enrollment
* Serum bilirubin \< 1.5 mg/dl performed within 60 days of enrollment
* Serum glutamic-oxaloacetic transaminase (SGOT) \< 2 x upper limit of normal (ULN) performed within 60 days of enrollment
* Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment or survival
* Patients must have a baseline left ventricular ejection fraction (LVEF) measured by multi-gated acquisition scan (MUGA) equal to or greater than the lower limit of normal for the radiology facility and if there are two consecutive MUGAS performed while on trastuzumab from the same radiology facility, there cannot be a decrease in LVEF of \> 15% from the original MUGA scan

Exclusion Criteria:

* Subjects cannot be simultaneously enrolled on other treatment studies
* Any contraindication to receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) based vaccine products
* Cardiac disease, specifically restrictive cardiomyopathy, unstable angina within the last 6 months prior to enrollment, New York Heart Association functional class III-IV heart failure on active treatment with normalized LVEF on therapy, and symptomatic pericardial effusion
* Active autoimmune disease
* Subjects cannot have an active immunodeficiency disorder, e.g. human immunodeficiency virus (HIV)

Primary outcomes:
measure: Immune Response Measured by IFN-gamma Secreting PBMC Precursor Frequency by ELIspot and HLA-A2 Major Histocompatibility Complex Tetramer Analysis
timeFrame: Up to 1.5 years (12 months following the last vaccination)
measure: Number of Adverse Events Graded Using National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0
timeFrame: Up to 7 months (30 days following the last vaccination)
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 5 years
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:
citation: Disis ML, Wallace DR, Gooley TA, Dang Y, Slota M, Lu H, Coveler AL, Childs JS, Higgins DM, Fintak PA, dela Rosa C, Tietje K, Link J, Waisman J, Salazar LG. Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. J Clin Oncol. 2009 Oct 1;27(28):4685-92. doi: 10.1200/JCO.2008.20.6789. Epub 2009 Aug 31.