Vaccine Therapy, Trastuzumab, and Vinorelbine in Treating Women With Locally Recurrent or Metastatic Breast Cancer
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| ClinicalTrials.gov Identifier: NCT00088985 |
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Recruitment Status :
Terminated
(Funding unavailable)
First Posted : August 5, 2004
Results First Posted : May 9, 2017
Last Update Posted : June 20, 2017
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RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as vinorelbine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining vaccine therapy with monoclonal antibody therapy and chemotherapy 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 women with locally recurrent or metastatic breast cancer.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Cancer | Biological: therapeutic autologous dendritic cells Biological: trastuzumab Drug: vinorelbine ditartrate | Phase 2 |
OBJECTIVES:
Primary
- Determine the efficacy of multiepitope autologous dendritic cell vaccine, trastuzumab (Herceptin^®), and vinorelbine by measuring the change in the largest dimension of metastatic lesions, in women with locally recurrent or metastatic breast cancer that does not overexpress human epidermal growth factor receptor 2 (HER2)/neu.
Secondary
- Determine the ability of this regimen to induce functional antigen-specific T cells in these patients by measuring ex-vivo antigen-specific T-cell activity against peptide-pulsed dendritic cells and tumor targets by tetramer staining and intracellular cytokine assays.
OUTLINE:
- Autologous dendritic cell mobilization and harvest: All patients undergo autologous dendritic cell mobilization with filgrastim (G-CSF) and/or sargramostim (GM-CSF) subcutaneously daily for 4 days followed by apheresis. Mobilized peripheral blood is processed for the production of dendritic cells by cluster of differentiation (CD)34-positive cell selection. The dendritic cells are expanded and then pulsed with E75 and E90 peptides.
- Treatment: Patients receive vinorelbine IV over 6-10 minutes and trastuzumab (Herceptin ^®) IV over 90 minutes on day 1. Patients also receive autologous dendritic cells pulsed with E75 and E90 peptides subcutaneously over 2-5 minutes on day 1*. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Note: *If treatment is given locally, the vaccine therapy will be given at University of North Carolina (UNC) -Chapel Hill the following day.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 17-37 patients will be accrued for this study.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 56 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase II Trial Evaluating The Efficacy Of A Multiepitope Dendritic Cell Vaccine Given With Trastuzumab And Vinorelbine For The Treatment Of Women With Metastatic Breast Cancer That Express HLA-A0201 |
| Study Start Date : | January 2004 |
| Actual Primary Completion Date : | October 2009 |
| Actual Study Completion Date : | October 2009 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dendritic Cell Vaccine
Dendritic Cells: Dosage: 20 x 106 dendritic cells (DCs) given per treatment Vinorelbine:25 mg/m2 will be administered i.v biweekly Trastuzumab: 6mg/Kg administered by i.v. biweekly
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Biological: therapeutic autologous dendritic cells
10 μg/kg subcutaneously (sc) each day for four days or g-CSF at 5 μg/kg sc each day for four days with GM-CSF 250 μg/m2 sc each day for four days. G-CSF and/or GM- CSF will be self-administered. On the fifth day patients will have two intravenous lines placed in the apheresis area of the Blood Bank and then undergo a 15 litre apheresis collection Biological: trastuzumab 4 mg/kg intravenously, every 14 days Drug: vinorelbine ditartrate Vinorelbine 25 mg/m2 will be administered intravenously, every 14 days |
- Overall Response Rate [ Time Frame: 6 months following treatment ]
Response measured by Response Evaluation Criteria In Solid Tumors (RECIST), (Complete Response + Partial Response)
Complete Response (CR)- Disappearance of all target lesions
Partial Response (PR)-at least a 30% decrease in the longest diameters of target lesions, taking as reference the baseline longest diameter.
- Immune Response [ Time Frame: 3 months following treatment ]Measured by intracellular cytokine staining for Interferon-gamma (INFgamma) and cluster of differentiation (CD107) up regulation and tetramer. A fourfold increase in the number of cluster of differentiation (CD8+) tetramers comparing prevaccine with peak postvaccine values indicated an immune response to the therapy.
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| Ages Eligible for Study: | 18 Years to 120 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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Histologically confirmed breast cancer
- Locally recurrent or metastatic disease
- HLA-A0201 positive by DNA genotyping
- HER2/neu expression at least 1+ by immunohistochemistry of tumor sample
- Central Nervous System (CNS) metastases allowed provided on therapy for 3 months and stable
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Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age
- 18 and over
Sex
- Female
Menopausal status
- Not specified
Performance status
- Eastern Cooperative Oncology Group (ECOG) 0-2
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count > 1,500/mm^3
- Platelet count > 100,000/mm^3
- Hematocrit > 33%
Hepatic
- Transaminases ≤ 3 times upper limit of normal
- Bilirubin ≤ 2 times normal
- Hepatitis B surface antigen negative
Renal
- Creatinine < 2.0 mg/dL
Cardiovascular
- Ejection fraction > 45% by multigated acquisition scan (MUGA) OR
- Left ventricular function normal by echocardiogram
- No serious cardiac condition that would preclude study participation or compliance
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No serious medical or psychiatric condition that would preclude study participation or compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Prior biologic therapy allowed
Chemotherapy
- More than 30 days since prior cytotoxic chemotherapy
- No other concurrent chemotherapy
Endocrine therapy
- More than 30 days since prior hormonal therapy
- No concurrent hormonal therapy
- No concurrent systemic steroids
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- Concurrent bisphosphonates for bone metastases allowed
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00088985
| United States, North Carolina | |
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | |
| Chapel Hill, North Carolina, United States, 27599-7295 | |
| Study Chair: | Jonathan S. Serody, MD | UNC Lineberger Comprehensive Cancer Center |
| Responsible Party: | UNC Lineberger Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00088985 |
| Other Study ID Numbers: |
LCCC 0310 P50CA058223 ( U.S. NIH Grant/Contract ) R21CA105837 ( U.S. NIH Grant/Contract ) KG100307 ( Other Grant/Funding Number: Susan G Komen for the Cure ) |
| First Posted: | August 5, 2004 Key Record Dates |
| Results First Posted: | May 9, 2017 |
| Last Update Posted: | June 20, 2017 |
| Last Verified: | May 2017 |
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recurrent breast cancer stage IIIB breast cancer stage IIIC breast cancer stage IV breast cancer |
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Trastuzumab Vinorelbine |
Antineoplastic Agents, Immunological Antineoplastic Agents Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |