Clinical trial NCT00266110: Vaccine Therapy, Trastuzumab, and Vinorelbine in Treating Patients With Locally Recurrent or Metastatic Breast Cancer
Official title: Phase II Trial Evaluating the Toxicity and Efficacy of a Multiepitope Dendritic Cell Vaccine Given With Trastuzumab and Vinorelbine Ditartrate for the Treatment of Women With Metastatic Breast Cancer That Express HLA-A0201 and Whose Tumors Overexpress HER-2/NEU
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Susan G. Komen Breast Cancer Foundation
First posted: 2005-12-15
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines made from a person's white blood cells may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vaccine therapy together with trastuzumab and vinorelbine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving vaccine therapy together with trastuzumab and vinorelbine works in treating patients with locally recurrent or metastatic breast cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the efficacy of multiepitope autologous dendritic cell vaccine in combination with trastuzumab (Herceptin®) and vinorelbine ditartrate in patients with locally recurrent or metastatic breast cancer whose tumors overexpress human epidermal growth factor receptor 2 (HER2/neu).

Secondary

* Determine if this regimen is effective in generating functional antigen-specific T cells.

OUTLINE:

* Therapeutic autologous dendritic cell (DC) preparation: Patients undergo mobilization of DC and apheresis for production of therapeutic DC. DCs are expanded in vitro for 10-20 days and pulsed with E75 and E90 peptides.
* Treatment: Patients receive vinorelbine ditartrate IV over 6-10 minutes, therapeutic autologous DC intradermally over 2-5 minutes, and trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Patients receive sargramostim (GM-CSF) subcutaneously on days 2, 4, and 6, or until neutrophil counts recover. Treatment repeats every 14 days for up to 6 courses (or more at the discretion of the investigator) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

Eligibility criteria: PATIENT ELIGIBILITY

4.1 Inclusion Criteria 4.1.1 Histologically proven metastatic breast cancer with measurable or evaluable disease per investigator discretion.

4.1.2 Patients must be 18 years of age or older. Women of child bearing potential must be practicing barrier or oral contraception for the duration of the study, or documented as surgically sterile or one year post-menopausal.

4.1.3 Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (See Appendix A).

4.1.5 Cardiac function by multigated acquisition scan (MUGA) with an ejection fraction (EF) \> 45% or an echocardiogram that shows normal left ventricle (LV) function.

4.1.6 Serum Creatinine \< 2.0 mg/dl. 4.1.7 Hepatic transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) ≤3.0 times the upper limit of normal if no liver metastases or ≤5 times the upper limit of normal if liver metastases are present.

4.1.8 Bilirubin no more than 2 times normal.

4.1.9 Seronegative for HIV.

4.1.10 Negative for Hepatitis B surface antigen.

4.1.11 Signed and dated informed consent.

4.1.12 HLA A0201+ by DNA genotyping.

4.1.13 Absolute neutrophil count greater than 1,500/mm3. Platelet count greater 100,000/mm3 and hemoglobin greater than or equal to 10

4.1.14. 3+ expression of HER-2/neu from original pathology (diagnostic) tumor sample by Immunohistochemistry (IHC) or 2+ expression by IHC with gene amplification by fluorescence in situ hybridization (FISH).

4.1.15. Patients will be eligible even if they have failed treatment for metastatic breast cancer with trastuzumab and a chemotherapy agent other than vinorelbine or if they have progressed within 12 months of receiving adjuvant chemotherapy using trastuzumab and a taxane.

4.2 Exclusion Criteria

4.2.1 Patients with any serious medical, cardiac, or psychiatric condition which, in the opinion of the investigator, would make the patient unsuitable for study participation or would impede probable compliance with the protocol.

4.2.2 Patients with central nervous system metastases must have stable disease for at least 3 months prior to study entry.

4.2.3 Patient is currently taking steroid medications. Systemic steroid treatment is not allowed.

4.2.4 Patients that have failed prior therapy with vinorelbine + trastuzumab will not be eligible for therapy.

4.2.5 Patient has received hormonal or cytotoxic chemotherapy within 14 days of apheresis and within 28-30 days prior to study treatment.

Primary outcomes:
measure: Number of Participants With Response
timeFrame: 5-6 years
Secondary outcomes:
measure: Generation of E75/E90 Tetramer-positive CD8+ T Cells
timeFrame: 13 weeks
measure: Generation of Interferon Gamma Positive CD8+T Cells
timeFrame: 13 weeks
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Jonathan S. Serody, MD
role: PRINCIPAL_INVESTIGATOR
References: