Breast CancerPhase 2NCT00266110
Vaccine Therapy, Trastuzumab, and Vinorelbine in Treating Patients With Locally Recurrent or Metastatic Breast Cancer
A Phase 2 study testing sargramostim, therapeutic autologous dendritic cells and trastuzumab in people with Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- sargramostim, therapeutic autologous dendritic cells and trastuzumab
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2005to 27 Oct 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7295
About this study
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
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- sargramostim, therapeutic autologous dendritic cells, trastuzumab, vinorelbine ditartrate
- Keywords
- stage IV breast cancer, recurrent breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sargramostimBiological
Also called 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 cellsBiological
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.
trastuzumabBiological
Also called 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 ditartrateDrug
Also called Navelbine
Vinorelbine 25 mg/m2 will be administered IV over six to ten minutes into the side port of a freely flowing IV line.
| Study group | Role | What they receive |
|---|---|---|
| Dendritic Cell Vaccine | Experimental | Therapeutic autologous dendritic cells (Dendritic Cell Vaccine) i.d. injection, 20 x 106 DCs given per treatment Trastuzumab infusion Vinorelbine ditartrate infusion Receives: Biological: sargramostim; Biological: therapeutic autologous dendritic cells; Biological: trastuzumab; Drug: vinorelbine ditartrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Response
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.
Measured: 5-6 years
Secondary outcomes (2)
Generation of E75/E90 Tetramer-positive CD8+ T Cells
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
Measured: 13 weeks
Generation of Interferon Gamma Positive CD8+T Cells
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
Measured: 13 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2005 (estimated)
- Study startDec 2005
- Primary completionFeb 2013
- Study completion27 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Susan G. Komen Breast Cancer Foundation
- Responsible party
- Sponsor
- Investigators
- Jonathan S. Serody, MD, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00266110
- Sponsor's protocol ID
- LCCC 0418
- Other IDs
- P50CA058223, R21CA105837, KG100307
- Status last verified
- Aug 2018
- First submitted
- 13 Dec 2005
- Last updated
- 12 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00266110
- Acronym / sponsor ID
- LCCC 0418
- Conditions
- Breast Cancer
- Keywords
- stage IV breast cancer, recurrent breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Susan G. Komen Breast Cancer Foundation
- Study start
- Dec 2005 (actual)
- Primary completion
- Feb 2013 (actual)
- Study completion
- 27 Oct 2017 (actual)
- First posted
- 15 Dec 2005 (estimated)
- Results
- Posted 9 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dendritic Cell Vaccine | Experimental | Biological: sargramostim, Biological: therapeutic autologous dendritic cells, Biological: trastuzumab, Drug: vinorelbine ditartrateTherapeutic autologous dendritic cells (Dendritic Cell Vaccine) i.d. injection, 20 x 106 DCs given per treatment Trastuzumab infusion Vinorelbine ditartrate infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sargramostimAlso: LeukineAll 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. | Biological | Dendritic Cell Vaccine |
| therapeutic autologous dendritic cellspatients 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 | Dendritic Cell Vaccine |
| trastuzumabAlso: HerceptinTrastuzumab 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. | Biological | Dendritic Cell Vaccine |
| vinorelbine ditartrateAlso: NavelbineVinorelbine 25 mg/m2 will be administered IV over six to ten minutes into the side port of a freely flowing IV line. | Drug | Dendritic Cell Vaccine |
Primary outcome
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.
2 secondary outcomes
Generation of E75/E90 Tetramer-positive CD8+ T Cells
Time frame: 13 weeks
Generation of Interferon Gamma Positive CD8+T Cells
Time frame: 13 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- web address for Lineberger Comprehensive Cancer Center, University of North Carolina (UNC)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan S. Serody, MD principal investigator
UNC Lineberger Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sargramostim, therapeutic autologous dendritic cells and trastuzumab in people with Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Response (time frame: 5-6 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2018.