NCT04134312已完成1 期
A Phase 1 Open Label Trial of Intravenous Administration of MVA-BN-Brachyury Vaccine in Patients With Advanced Cancer
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- Patients with Dose Limiting Toxicity (DLT)
研究概览
简要总结
A Phase 1 open label trial of intravenous administration of MVA-BN-Brachyury vaccine in patients with advanced cancer. Patients with metastatic or unresectable locally advanced malignant solid tumors will be enrolled and treated according to a 3+3 dose escalation scheme. Up to 3 dose levels will be explored. Patients will receive MVA-BN-Brachyury every three weeks, three administrations in total. Patients will be hospitalized after each vaccination, over 48 hours. Trial duration will be approximately 24 weeks per patient including 3 months after the last vaccination follow up (FU) period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Men and women > 18 years old.
- •Patients must be able to understand and be willing to sign a written informed consent document.
- •Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
- •Eligible patients must have one of the histologically confirmed cancers and treatment history as described:
- •Symptomatic, unresectable, locally recurrent, or metastatic tumors are acceptable for enrollment, given that this represents incurable disease.
- •Only curative interventions are required as prior therapy (surgery or definitive radiation) as no known systemic therapies have proven benefit.
- •Non-Small Cell Lung Cancer
- •Metastatic or incurable locally advanced.
- •Disease progression after indicated targeted therapy (EGFR-mut, ALK-fusion, BRAF-mut).
- •Disease progression after one regimen of chemotherapy and anti-PD-1/L1 therapy either sequentially or concurrently.
- •Small Cell Lung Cancer
- •Metastatic disease.
- •Disease progression after 1st line chemotherapy.
- •Metastatic disease considered to be incurable.
- •Triple negative - disease progression after first line chemotherapy.
- •ER+ disease - must have had disease progression through at least 2 lines of hormonal therapy and at least 1 chemotherapy regimen.
- •Her2+ disease - must have had disease progression after at least 2 Her2-targeted therapy containing regimens.
- •ER+ and Her2+ - must meet requirements of each tumor marker subtype (see above).
- •Metastatic disease.
- •Disease progression after treatment with platinum-based chemotherapy.
- •Metastatic Castration Resistant Prostate Cancer (mCRPC) AND
- •Disease progression after at least one line of treatment of abiraterone or enzalutamide and docetaxel.
- •Colorectal
- •Metastatic disease.
- •Must have received chemotherapy regimens containing 5-FU, oxaliplatin, irinotecan, and EGFR-targeted antibodies when indicated (absence of RAS mutation) with evidence of disease progression or AEs that preclude further treatment with standard therapies.
- •Pancreatic
- •Metastatic disease.
- •Disease progression after or intolerance to standard chemotherapy regimens of known benefit (FOLFIRINOX or Gemcitabine and Abraxane).
- •Hepatocellular
- •Incurable disease: liver only or metastatic.
- •Disease progression after at least one systemic therapy of known benefit (e.g. sorafenib).
- •Metastatic disease.
- •At least one line of chemotherapy and immune checkpoint inhibitors second line.
- •Metastatic disease.
- •After VEGF inhibitors, immune check-point inhibitors, m-TOR inhibitors.
- •Patients must have measurable or evaluable disease. Measurable disease is defined by RECIST 1.
- •In the case of evaluable disease, patients should have cancer-related symptoms to justify risk.
- •Evaluable disease is defined as any of the following:
- •Elevated serum tumor marker known to be related to the patient's tumor.
- •Clear radiographic or physical exam evidence of tumor which does not meet RECIST 1.1 measurement requirements.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Patients must have normal organ and bone marrow function as defined below:
- •Renal function:
- •Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
- •Female CrCl = [(140 - age in years) x weight in kg x 0.85] / [72 x serum creatinine in mg/dL]
- •Male CrCl = [(140 - age in years) x weight in kg x 1.00] / [72 x serum creatinine in mg/dL]
- •Liver function:
- •Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 x the ULN.
- •Total bilirubin ≤ 1.5 x ULN (in subjects with Gilbert's syndrome a total bilirubin ≤ 3.0 x ULN), or < 5 x ULN, if liver metastases are present.
- •Hematological parameters (within one week of starting therapy):
- 另有 11 项未显示
排除标准
- •Receipt of an investigational agent within 28 days of the first planned dose of MVA-BN-Brachyury vaccine.
- •Concurrent chemotherapy or radiotherapy or other immunotherapy not explicitly allowed by inclusion criteria for this trial.
- •Known metastatic disease to the central nervous system, unless previously treated and well controlled for at least 3 months (clinically stable, no edema, no steroid treatment required).
- •History of anaphylaxis or severe allergic reaction to any vaccine, aminoglycoside antibiotics or egg products.
- •Active infection within 72 hours prior to vaccination.
- •Administration of antibiotics within 7 days prior to initial vaccination.
- •Subjects having known evidence of being immunocompromised as listed below:
- •Human immunodeficiency virus (HIV) positivity, active chronic hepatitis infection, including B and C.
- •Active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, and psoriasis not requiring systemic treatment are permitted.
- •Immunosuppressive therapy for post-organ transplant.
- •Chronic administration (defined as > 5 consecutive days of > 15 mg of prednisone (or equivalent) per day) of systemic corticosteroids within 14 days of the first planned dose of MVA-BN-Brachyury vaccine. Use of inhaled steroids, nasal sprays, eye drops, and topical creams is allowed. Steroids premedication for CT scans is allowed.
- •Vaccinations or planned vaccinations with a live vaccine within 30 days prior to the trial vaccination or with an inactivated vaccine within 14 days prior to the trial vaccination.
- •Patients with history of myocardial infarction, unstable angina pectoris, history of or existing CHF (NYHA Class II -IV), other cardiomyopathy, cardiac arrhythmia requiring medical treatment, clinically significant cardiac valvular disease, poorly controlled hypertension and hemodynamic effective pericardial effusion.
- •Known history of, or any evidence of active, non-infectious pneumonitis or primary pulmonary fibrosis.
- •Psychiatric illness/social situations that, in the opinion of the Investigator, would limit compliance with trial requirements.
- •Pregnant or breastfeeding women.
- •Any other condition, which in the opinion of the Investigator, would indicate the subject is a poor candidate for treatment with MVA-BN-Brachyury vaccine or would interfere with the evaluation of the trial endpoints.
结局指标
主要结局
Patients with Dose Limiting Toxicity (DLT)
时间窗: DLT assessment is done 7 days after 2nd vaccination of last patient in each dose level
Frequency of patients with DLTs
次要结局
未报告次要终点
研究者
研究点 (2)
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