Phase 1/2a, Dose-Escalation, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Intratumoral Administration of DTA-H19 in Patients With Unresectable Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 5
- 主要终点
- Maximal Tolerated Dose (MTD) & Dose Limiting Toxicity (DLT) of Intratumoral Injections of BC-819
研究概览
简要总结
This study is designed to assess the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of DTA-H19 administered intratumorally in patients with unresectable, locally advanced pancreatic cancer.
Primary Objective: The primary objective is to determine the maximum tolerated dose (MTD) of intratumoral DTA-H19 and identify any dose limiting toxicities (DLTs).
Secondary objectives include determining the adverse events (AEs) profile, effects on clinical laboratory analytes, vital signs, PK, tumor response, and possible tumor resectability after 4 intratumoral administrations of DTA-H19.
详细描述
DTA-H19, is a doubled stranded DNA plasmid that carries the gene for the diphtheria toxn A (DT-A) chain under the regulation of the H19 promoter sequence. This is a Patient-Oriented, Targeted Therapy as DT-A chain expression is triggered by the presence of H19 transcription factors that are upregulated in tumor cells. The selective initiation of toxin expression results in selective tumor cell destruction via inhibition of protein synthesis in the tumor cell, enabling highly targeted cancer treatment.
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide written informed consent and be between the ages of 18 and 79, inclusive.
- •Have unresectable, locally advanced adenocarcinoma of the pancreas proven by biopsy or cytology (defined as direct extension to the superior mesenteric artery and/or celiac axis with loss of a clear plane between tumor and these arterial structures, or loss of patent superior mesenteric-portal vein confluence). Patients who have been surgically explored and deemed unresectable on that basis are eligible, provided other entry criteria are met. Patients having potentially resectable regional lymph node involvement may be included.
- •Have a target tumor ≤ 6 cm in diameter that is accessible for intratumoral administration by PTA or EUS guidance as determined by the radiologist/gastroenterologist performing the PTA/EUS injection.
- •Have a Karnofsky performance status of ≥ 70%.
- •Have a life expectancy of >= 3 months.
- •If female and of child-bearing potential, have a negative serum pregnancy test during screening.
- •Agree to use of a barrier method of contraception if sexually active (both men and women) from the time of administration of the first treatment and for at least 8 weeks after treatment.
- •Have serum creatinine < 2.0 mg/dL, AST and ALT >= 2.5 x ULN, PT, PPT, and PT/INR within normal limits, absolute neutrophil count (ANC) > 1,500 x 103 cells/mL, platelets ≥ 100,000/mL, and hemoglobin >= 10 mg/dL.
- •Have a biopsy specimen that is positive for H19 expression (grade 2 or greater staining determined by a pathologist).
- •Have screening procedures completed within 4 weeks of starting treatment.
- •No other malignancy present that would interfere with the current intervention.
- •Commit to refrain from any concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while on this protocol, therefore any standard treatment should be postponed while on study.
- •Have measurable disease.
排除标准
- •Have distant metastatic spread (such as liver or lung metastases), peritoneal spread or malignant ascites.
- •Have prior radiation therapy for pancreatic cancer or radiation to the area of the target tumor field.
- •Endocrine tumors or lymphoma of the pancreas.
- •Have clinically significant pancreatitis within 12 weeks of treatment.
- •If female, be breast feeding.
- •Have a medical condition contraindicated for both percutaneous- and endoscopic- guided delivery or any intercurrent medical illness or other medical condition that would in the judgment of the investigator compromise patient safety or the objectives of the study.
- •Have a history of coagulopathy.
- •Have participated in any therapeutic research study within the last 4 weeks.
研究组 & 干预措施
BC-819
Intratumoral administration of BC-819
干预措施: DTA-H19 (Biological)
结局指标
主要结局
Maximal Tolerated Dose (MTD) & Dose Limiting Toxicity (DLT) of Intratumoral Injections of BC-819
时间窗: Week 4
If 2 patients in any cohort experience DLTs, then the next lower dose will be considered the MTD if there is a lower dose cohort. A DLT is defined as grade 3 or greater toxicity judged to be at least possibly related to the investigational products.
次要结局
- Tumor Response(4 weeks)
- Tumor Resectability(5 to 6 weeks)