A Pilot Study Utilizing a HER2 Directed Dendritic Cell Vaccine During Neoadjuvant Therapy of HER2+ Breast Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Expansion Phase Schedule Selection by Week 4
研究概览
简要总结
The purpose of this study is to learn more about how to treat patients with HER-2/neu positive invasive breast cancer (IBC). HER-2/neu is a type of protein that is known to be over-expressed in aggressive breast cancer.
The study drug for this trial is DC1 study vaccine which is a HER2-sensitized dendritic cell (DC) study vaccine. This study vaccine is made from the participant's blood cells collected from a procedure called leukapheresis. Dendritic cells are immune cells that can tell the immune system to fight infection. In laboratory testing and from previous studies in participants, these cells may also help the immune system attack tumors such as breast cancer.
详细描述
The trial will consist of two phases. The first lead in phase will enroll 12 participants evenly divided into two arms (alternating enrollment) with different initial priming study vaccination schedules.
Arm A: One DC1 study vaccination per week x 3 weeks. Arm B: Two DC1 study vaccinations per week (given 3 days apart for example Mon and Thurs or Tues and Friday) x 3 weeks.
Following accrual of this initial group of 12 participants, HER2 ELISPOT post study vaccination responses will be assessed to determine which of the two sequences provides the greater increase in anti HER2 response at week 4 over baseline. This will determine which sequence will be used in the second expansion phase of accrual. If both arms are determined equal then Arm A will be selected as the default sequence.
Second phase of accrual will consist of 14 additional participants to undergo study vaccination using the optimal schedule declared in the first phase of the trial. The trial will consist of two phases. The first lead in phase will enroll 12 participants evenly divided into two arms (alternating enrollment) with different initial priming study vaccination schedules.
Arm A: One DC1 study vaccination per week x 3 weeks Arm B: Two DC1 study vaccinations per week (given 3 days apart for example Mon and Thurs or Tues and Friday) x 3 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have histologically confirmed clinical stage II or III ERPR- HER2+ (per CAP criteria) invasive carcinoma of the breast
- •Medically and surgically appropriate to undergo neoadjuvant chemotherapy with TCH-P Taxotere (docetaxel), Carboplatin, Herceptin (trastuzumab), Perjeta (pertuzumab) regimen followed by standard of care local therapy as determined by their treating physician
- •Age ≥18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status less than 2
- •Patients must have normal organ and marrow function as defined below:
- •leukocytes ≥3,000/μL
- •absolute neutrophil count ≥1,500/μL
- •platelets ≥100,000/μL
- •total bilirubin within normal institutional limits
- •AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal
- •creatinine within normal institutional limits - OR -
- •creatinine clearance ≥60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Cardiac ejection fraction within institutional normal limits by either MUGA or ECHO at baseline.
- •Women of child-bearing potential and their male partners must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Sexually active male participants should use a barrier method or exercise abstinence during chemotherapy administration until surgery.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Patients with inflammatory breast cancer, widespread locally advanced unresectable disease involving the chest wall/nodal basins in which a curative surgical resection cannot be performed, or those in whom de novo metastatic disease is suspected or confirmed
- •May not be receiving any other investigational agents for the treatment of their breast cancer.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study vaccine components and any of the chemotherapy drugs (docetaxel, carboplatin, trastuzumab, pertuzumab)
- •Unwilling or unable to undergo an apheresis for production of their vaccine
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Women who are pregnant or breastfeeding
- •Known congenital or acquired immune deficiency (including those patients who require systemic immunosuppressant drugs for autoimmune disease or organ transplant).
- •Pre-existing peripheral neuropathy that would limit treatment with taxanes and platinum agents
研究组 & 干预措施
Lead In Phase - Arm A
Arm A: One Dendritic Cell Vaccine (DC1) per week x 3 weeks.
干预措施: Dendritic Cell Vaccine (DC1) (Biological)
Lead In Phase - Arm A
Arm A: One Dendritic Cell Vaccine (DC1) per week x 3 weeks.
干预措施: Neoadjuvant Chemotherapy (Drug)
Lead In Phase - Arm B
Arm B: Two DC1 vaccinations per week (given 3 days apart i.e., Mon and Thurs or Tues and Friday) x 3 weeks.
干预措施: Curative Surgery (Procedure)
Lead In Phase - Arm A
Arm A: One Dendritic Cell Vaccine (DC1) per week x 3 weeks.
干预措施: Curative Surgery (Procedure)
Expansion Phase
DC1 vaccinations according to optimal vaccination schedule. Participants will receive a booster intranodal study vaccine at week 25 prior to receiving surgery. Participants will then undergo definitive curative surgery following completion of the neoadjuvant therapy, additional adjuvant locoregional/systemic therapy (as deemed appropriate by their treating physicians).
干预措施: Dendritic Cell Vaccine (DC1) (Biological)
Lead In Phase - Arm B
Arm B: Two DC1 vaccinations per week (given 3 days apart i.e., Mon and Thurs or Tues and Friday) x 3 weeks.
干预措施: Dendritic Cell Vaccine (DC1) (Biological)
Lead In Phase - Arm B
Arm B: Two DC1 vaccinations per week (given 3 days apart i.e., Mon and Thurs or Tues and Friday) x 3 weeks.
干预措施: Neoadjuvant Chemotherapy (Drug)
Expansion Phase
DC1 vaccinations according to optimal vaccination schedule. Participants will receive a booster intranodal study vaccine at week 25 prior to receiving surgery. Participants will then undergo definitive curative surgery following completion of the neoadjuvant therapy, additional adjuvant locoregional/systemic therapy (as deemed appropriate by their treating physicians).
干预措施: Neoadjuvant Chemotherapy (Drug)
Expansion Phase
DC1 vaccinations according to optimal vaccination schedule. Participants will receive a booster intranodal study vaccine at week 25 prior to receiving surgery. Participants will then undergo definitive curative surgery following completion of the neoadjuvant therapy, additional adjuvant locoregional/systemic therapy (as deemed appropriate by their treating physicians).
干预措施: Curative Surgery (Procedure)
结局指标
主要结局
Expansion Phase Schedule Selection by Week 4
时间窗: By Week 4
Immunogenicity of HER2 DC Vaccine per treatment Arm, based on week 4 ELISPOTs. Three metrics of CD4+ Th1 response will be computed for each patient, (a) overall anti-HER2 responsivity (i.e., if patient demonstrates a positive ELISPOT response to \>1 peptide, (b) response repertoire (i.e., number of reactive peptides) and (c) cumulative response (total SFC/10\^6 cells across 6 peptides). The primary immunogenicity outcome will be the cumulative response at week 4 (week after completion of all vaccinations).
Pathologic Complete Response (pCR) Rate
时间窗: Week 26 to 28 - At post-surgical pathological assessment
Pathologic complete response rate of participants treated in the Expansion Phase. Clinical efficacy will be defined by the pathologic complete response (pCR) rate, the percentage of patients who achieve pCR based on surgical pathology assessment.The definition of pathologic complete response (pCR) will be ypT0/is N0 (no residual viable invasive disease in the breast or nodes). Any response less than pCR will be scored as incomplete response or progression (if tumor size increases during neoadjuvant chemotherapy on physical exam/breast imaging).
次要结局
- Recurrence Free Survival (RFS)(Up to 3 years post-surgery)