Vaccine Therapy, Trastuzumab, and Vinorelbine in Treating Patients With Locally Recurrent or Metastatic Breast Cancer

• ClinicalTrials.gov Identifier: NCT00266110
• Recruitment Status: Completed
• First Posted: December 15, 2005
• Results First Posted: May 9, 2017
• Last Update Posted: September 12, 2018
• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI); Susan G. Komen Breast Cancer Foundation
• Information provided by (Responsible Party): UNC Lineberger Comprehensive Cancer Center

Tracking Information

• First Submitted Date: December 13, 2005
• First Posted Date: December 15, 2005
• Results First Submitted Date: March 28, 2017
• Results First Posted Date: May 9, 2017
• Last Update Posted Date: September 12, 2018
• Actual Study Start Date: December 2005
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2017)

Number of Participants With Response [ Time Frame: 5-6 years ]

Response: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

• Original Primary Outcome Measures (submitted: December 13, 2005): - To test the efficacy of giving a multiepitope DC vaccine with trastuzumab and vinorelbine using RECIST criteria

Current Secondary Outcome Measures (submitted: August 14, 2018)

• Generation of E75/E90 Tetramer-positive CD8+ T Cells [ Time Frame: 13 weeks ]
  Evaluate the ability of peptide-pulsed dendritic cells plus trastuzumab to induce functional antigen specific T cells. Measured by percentage of intracellular cytokine staining for E75/E90 tetramer-positive CD8+ T cells
• Generation of Interferon Gamma Positive CD8+T Cells [ Time Frame: 13 weeks ]
  Evaluate the ability of peptide-pulsed dendritic cells plus trastuzumab to induce functional antigen specific T cells. Measured by percentage of intracellular cytokine staining for interferon gamma positive CD8+ T cells

• Original Secondary Outcome Measures (submitted: December 13, 2005): - Evaluate effectiveness in generating functional antigen-specific T cells by measuring ex vivo antigen-specific T cell activity against peptide-pulsed and tumor targets.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Biological: sargramostim
  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.
  Other Name: Leukine
• Biological: 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.
• Biological: trastuzumab
  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.
  Other Name: Herceptin
• Drug: 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.
  Other Name: Navelbine

Study Arms

Experimental: Dendritic Cell Vaccine

Therapeutic autologous dendritic cells (Dendritic Cell Vaccine) i.d. injection, 20 x 106 DCs given per treatment Trastuzumab infusion Vinorelbine ditartrate infusion

Interventions:

• Biological: sargramostim
• Biological: therapeutic autologous dendritic cells
• Biological: trastuzumab
• Drug: vinorelbine ditartrate

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 28, 2017): 17
• Original Enrollment (submitted: December 13, 2005): 26
• Actual Study Completion Date: October 27, 2017
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00266110
• Other Study ID Numbers: LCCC 0418; P50CA058223 ( U.S. NIH Grant/Contract ); R21CA105837 ( U.S. NIH Grant/Contract ); KG100307 ( Other Grant/Funding Number: Susan G Komen for the Cure )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: UNC Lineberger Comprehensive Cancer Center
• Original Responsible Party: Not Provided
• Current Study Sponsor: UNC Lineberger Comprehensive Cancer Center
• Original Study Sponsor: Same as current

Collaborators

• National Cancer Institute (NCI)
• Susan G. Komen Breast Cancer Foundation

Investigators

• Principal Investigator: Jonathan S. Serody, MD; UNC Lineberger Comprehensive Cancer Center

• PRS Account: UNC Lineberger Comprehensive Cancer Center
• Verification Date: August 2018