A Multiantigen Vaccine (STEMVAC) for Adjuvant Treatment of Patients With Moderate or Extensive Residual Triple-Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Invasive breast cancer free survival (IBCFS)
研究概览
简要总结
This phase II trial evaluates whether a multi-antigen vaccine called STEMVAC improves disease-free survival after surgery in patients with triple-negative breast cancer (TNBC) and moderate or extensive residual cancer burden. TNBC has an aggressive clinical course and poorer disease-free survival compared to other subtypes. While patients who have no remaining tumor in the breast or lymph nodes after surgery have excellent long-term outcomes, patients with moderate or extensive residual cancer burden remain at high risk for early disease return and poorer prognosis. STEMVAC is designed to target proteins that tumor cells use when they become more aggressive and start to spread, and it is believed to work by boosting the immune system to recognize and destroy the invader tumor cells that are causing the disease. Giving STEMVAC after surgery may improve disease-free survival rates in TNBC patients with moderate or extensive residual cancer burden.
详细描述
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid deoxyribonucleic acid (DNA) vaccine (STEMVAC) with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) intradermally (ID) every 3 weeks for 3 doses. Patients then receive booster vaccines ID 9 weeks after vaccine 3 and 18 weeks after booster 1. Patients also undergo collection of blood samples throughout the trial.
ARM B: Patients receive GM-CSF ID every 3 weeks for 3 doses. Patients then receive booster vaccines ID 9 weeks after vaccine 3 and 18 weeks after booster 1. Patients also undergo collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up at 3 weeks after their last vaccination and then every 6 months for 3 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •At least 18 years of age
- •Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2
- •Triple-negative breast cancer as determined by the treating oncologist
- •Completed standard of care neoadjuvant chemotherapy in the opinion of their treating oncologist
- •Patients whose tumors progress on neoadjuvant therapy may be enrolled
- •No clinical evidence of local or distant recurrence
- •Plan to receive standard of care adjuvant directed therapy
- •Completed standard of care locoregional treatment, including definitive breast and lymph node surgery followed by standard radiation therapy, if recommended
- •Residual cancer burden (RCB) index 2 or 3 as calculated per routine anatomic pathology clinical standards
- •Absolute neutrophil count (ANC) ≥ 800/μL (within 30 days of first study vaccine administration)
- •Hemoglobin (Hgb) ≥ 8 g/dL (within 30 days of first study vaccine administration)
- •Platelets ≥ 75,000/ μL (within 30 days of first study vaccine administration)
- •Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome, in whom total bilirubin must be < 3.0 mg/dL (within 30 days of first study vaccine administration)
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN (within 30 days of first study vaccine administration)
- •Creatinine ≤ 1.5 x ULN mg/dL or creatinine clearance > 60 mL/min (within 30 days of first study vaccine administration)
- •At least 28 days post systemic steroids prior to enrollment, unless used as part of prophylaxis to prevent intravenous (IV) contrast reactions.
- •Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption) are allowed
- •Must have recovered from major infections and/or surgical procedures; and in the opinion of the investigator, not have any significant active concurrent medical illnesses or condition precluding protocol treatment
- •Patients of child-bearing potential must agree to use dual methods of contraception and have a negative urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a person of child-bearing potential. Acceptable methods of contraception are abstinence, condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal
排除标准
- •Toxicities related to prior exposure to immune checkpoint inhibitors for which immune checkpoint inhibitors cannot be safely continued as determined by study investigator
- •Germline BRCA1 or BRCA2 mutations with adjuvant olaparib planned within the study period
- •NOTE: If olaparib is not planned, then these patients are eligible
- •Any known cardiac conditions:
- •Symptomatic restrictive cardiomyopathy
- •Dilated cardiomyopathy
- •Unstable angina within 4 months prior to enrollment
- •New York Heart Association functional class III-IV heart failure on active treatment
- •Symptomatic pericardial effusion
- •Autoimmune disease requiring active systemic treatment
- •Known hypersensitivity reaction to the GM-CSF adjuvant; any known contra-indication to GM-CSF
- •Pregnant or breast feeding
- •Known history of human immunodeficiency virus (HIV) infection, hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive), or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] is detected)
- •Major surgery within the 4 weeks prior to initiation of first study vaccine
- •Enrollment in any other clinical protocol or investigational trial that involves concurrent administration of experimental therapy and/or therapeutic devices, or investigational drug. Patients who completed prior clinical trials (such as neoadjuvant treatment, surgery or radiation trials) and are on long term follow up are permitted
结局指标
主要结局
Invasive breast cancer free survival (IBCFS)
时间窗: Time from randomization to local or distant recurrence or death, assessed up to 3 years
Kaplan-Meier curves will be generated with median estimation and 95% confidence interval, and log-rank tests will be conducted to compare the survival difference between groups. Will calculate the 3-year IBCFS rate with a 95% confidence interval from Kaplan-Meier methods using Greenwood standard errors.
Dynamics and characteristics of circulating tumor deoxyribonucleic acid (ctDNA)
时间窗: Up to 3 weeks after last vaccination
Through serial ctDNA evaluation, each sample will be assessed for ctDNA detectability and, if detectable, total ctDNA mass (continuous variable, as reported by the assay platform) will be calculated. ctDNA detectability and quantitative ctDNA measures will be summarized descriptively by timepoint and study arm, and changes over time will be evaluated using methods appropriate to the final endpoint definition, data distribution, and repeated-measures structure of the data. Associations with IBCFS will also be explored. Copy number variants (including aneuploidy, chromosome-level gains, losses, and amplifications, as defined by the final assay methodology) will also be tracked and tabulated, and changes over time will be evaluated descriptively in both study arms.
次要结局
- Incidence of adverse events(Up to 3 weeks after last vaccination)
- Immune response(Up to 3 weeks after last vaccination)
- Expression of epithelial to mesenchymal transformation (EMT)-associated genes(Archival tissue is collected after enrollment, within 30 days of baseline visit)