This trial is active, not recruiting.

Condition breast cancer
Treatments sargramostim, therapeutic autologous dendritic cells, trastuzumab, vinorelbine ditartrate
Phase phase 2
Target HER2
Sponsor UNC Lineberger Comprehensive Cancer Center
Collaborator National Cancer Institute (NCI)
Start date December 2005
End date December 2018
Trial size 26 participants
Trial identifier NCT00266110, LCCC 0418, P30CA016086


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
sargramostim Leukine
All patients will receive Leukine (GM-CSF) at 250 mcg/m2 starting one day after the administration of chemotherapy x 7 days. Patients with neutrophil counts below 1,000/mm3 on day 8 will continue GM-CSF therapy until the neutrophil count is greater than 1,000/mm3.
therapeutic autologous dendritic cells
patients will receive (10 x 106) peptide-pulsed DCs given by i.d injection into either axilla or the inguinal region with each peptide given into a separate site. The total dose will be 20 x 106 DCs given per treatment.
trastuzumab Herceptin
Trastuzumab will be infused in the side-port of a freely flowing IV over 90 minutes and at 6mg/kg if the subject has not previously received Trastuzumab, or if it has been more than 30 days since any prior trastuzumab administration. If the subject has previously received Trastuzumab within 30 days and has no adverse history with the drug, the infusion will be given over 30 minutes. If the subject is currently receiving Trastuzumab, the first study infusion will be given at 4mg/kg over 30 minutes. Subsequently, Trastuzumab will be infused at 4 mg/kg in the side-port of a freely flowing IV over 30 minutes.
vinorelbine ditartrate
Vinorelbine 25 mg/m2 will be administered IV over six to ten minutes into the side port of a freely flowing IV line.

Primary Outcomes

time frame: 5-6 years

Secondary Outcomes

Generation of functional antigen-specific T cells
time frame: 5-6 years

Eligibility Criteria

Male or female participants at least 18 years old.

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 ECOG performance status 0-2 (See Appendix A). 4.1.5 Cardiac function by MUGA with an EF > 45% or an echocardiogram that shows normal 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 2X 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 IHC or 2+ expression by IHC with gene amplification by 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.

Additional Information

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
Principal investigator Jonathan S. Serody, MD
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 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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by UNC Lineberger Comprehensive Cancer Center.