A Phase 1 Trial of Intratumoral Cisplatin for Early Stage, Resectable, Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Rate of Dose Limiting Toxicity
研究概览
简要总结
PRIMARY OBJECTIVE:
To identify the maximum tolerated dose (MTD) of intratumoral cisplatin, delivered during a single bronchoscopy with cone-beam CT confirmation, in a dose escalation protocol
DESIGN: 3+3 dose escalation.
详细描述
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States. Even for early stage disease, the rate of recurrence following surgical resection is as high as 50%. Although neoadjuvant therapy, administered before surgery, for early stage lung cancer is associated with a survival benefit, it is rarely used due to the systemic toxicity of intravenous (IV) cytotoxic chemotherapy. IV immunotherapies are also being evaluated in combination with systemic therapies in the neoadjuvant setting. However, only a minority of patients respond to immunotherapy. One of the most common reasons for failure of immunotherapy is lack of presentation of tumor antigens to the immune system, a problem that may be potentially addressed with cytotoxic agents.
Over the last several years, case series have demonstrated the feasibility and safety of delivering cisplatin directly into lung tumors. Given the current knowledge of safety and tolerability of intratumoral cisplatin, coupled with the potential to achieve immune priming that may help address systemic micrometastases, the investigators postulate that intratumoral cisplatin will be well-tolerated, and potentially effective, neoadjuvant therapy for patients with early stage, resectable, non-small cell lung cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Age ≥18 years.
- •Eastern Cooperative Oncology Group performance status 0 or 1
- •Patients must have adequate organ and marrow function as defined below:
- •Leukocytes ≥3,000/microliter
- •Platelets ≥100,000/microliter
- •Total bilirubin ≤ institutional upper limit of normal (ULN)
- •Aspartate aminotransferase /Alanine aminotransferase ≤3 × institutional upper limit of normal
- •Creatinine ≤ institutional ULN
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- •Have known or suspected clinical stage I-IIb NSCLC after computed tomography (CT) and/or positron emission tomography at time of enrollment
- •Presence of a target lesion with a minimum volume of 1.0 cm3, (approximately1.2 cm in diameter) and ≤ 5.0 cm in diameter
- •Agreement from a cardiothoracic surgeon, following review of past medical history, medications, pulmonary function testing, and CT scan that patient is likely to be a surgical candidate and that, after considering known possible adverse events, delivery of intratumoral cisplatin is unlikely to adversely affect surgical feasibility
- •Rapid on-site cytopathologic examination (ROSE) performed during the procedure returns likely NSCLC (per the determination of a trained, attending, cytopathologist). No research procedures will be performed if ROSE is non-diagnostic
- •A CT scan of the chest (with or without contrast) within 1 month of the screening visit
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Use of an investigational agent within 30 days of the screening visit
- •IV chemotherapy within the 30 days of the screening visit
- •Pregnancy/lactation (pregnancy test to be performed by pre-op as part of standard of care for women of child-bearing age as defined by University of Vermont Medical Center Policy
- •History of prior radiation to the study lesion
- •History of allergic reaction to cisplatin or its derivatives
- •Patients with uncontrolled intercurrent illness
- •Physician determination that patient would not be appropriate for study
研究组 & 干预措施
Intratumoral Cisplatin 20 mg
Second dose level
干预措施: cis-diamminedichloroplatinum (Drug)
Intratumoral Cisplatin 10 mg
First dose level
干预措施: cis-diamminedichloroplatinum (Drug)
结局指标
主要结局
Rate of Dose Limiting Toxicity
时间窗: Within 2 weeks of delivery
Adverse events as defined using the Common Terminology Criteria for Adverse Events
次要结局
- Major Pathologic Response(Assessed on the surgical resection specimen, performed within 30 days of bronchoscopic delivery)
研究者
C. Matthew Kinsey MD, MPH
Director, Interventional Pulmonary
University of Vermont