Neoadjuvant CAN-2409 Plus Prodrug in Combination With Chemoradiation or Stereotactic Body Radiation Therapy for Borderline Resectable Pancreatic Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 54
- 试验地点
- 6
- 主要终点
- Safety grade by CTCAE version 4.0
研究概览
简要总结
The purpose of this study is to characterize the safety, preliminary efficacy, and immune biologic activity of CAN-2409 + prodrug (valacyclovir or acyclovir) in subjects with borderline resectable pancreatic cancer who are being treated with neoadjuvant chemoradiation (CR) or stereotactic body radiation therapy (SBRT). The Standard of Care (SOC) Control arm will be used as a benchmark for informal comparisons of efficacy, safety, and biomarkers.
详细描述
Study design is an open-label Phase 2 trial that randomizes subjects with borderline resectable pancreatic adenocarcinoma to received SOC with (Test arm) or without (Control arm) the addition of CAN-2409 + prodrug (2:1 randomization, Test: Control), beginning after completion of at least 4 months (8 cycles) of a FOLFIRINOX based induction therapy. Confirmation of borderline resectable status will be based on central radiologic review following completion of FOLFIRINOX based induction regimen. Upon enrollment, eligible subjects will receive three courses of CAN-2409 + prodrug, the first course starting prior to CR or SBRT, the second course concurrent with CR or just following completion of SBRT, and the third at time of resection. Up to 2 additional courses are allowed at the time of disease recurrence.
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
- •Pathological diagnosis of pancreatic adenocarcinoma adequately treated with a FOLFIRINOX based induction chemotherapy for at least 4 months such that they are a candidate for localized therapy with CR or SBRT followed by surgery with or without major vascular resection.
- •Subjects must be deemed to be in adequate health to undergo major surgery (e.g., pancreaticoduodenectomy).
- •Tumor accessible for injection by EUS or CT-guidance, considered potentially resectable at time of diagnosis, and classified as borderline resectable based on central radiologic review of CT scans performed following completion of FOLFIRINOX based induction chemotherapy. Resection may include major vascular resection with reconstruction as needed.
- •Criteria for borderline resectable disease status:
- •No distant metastasis or lymph node involvement outside the planned resection field.
- •Venous involvement of the superior mesenteric vein (SMV) or portal view (PV) with distortion or narrowing of the vein or occlusion of the vein with suitable vessel proximal and distal, allowing for safe resection and replacement
- •Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct tumor abutment of the hepatic artery, without extension to the celiac axis
- •Tumor abutment of the superior mesenteric artery (SMA) not to exceed > 180 degrees of the circumference of the vessel wall
- •Age > 18 years at the time of consent
- •Performance status ECOG 0 or 1
- •SGOT (AST) <3x upper limit normal
- •Total bilirubin <2mg/dl
- •Subjects with biliary obstruction can be enrolled if AST and bilirubin do not meet criteria but must meet the criteria after stenting before starting treatment
- •Creatinine <2mg/dl
- •Calculated creatinine clearance > 30ml/min
- •WBC > 3000/mm^3
- •Absolute neutrophil count (ANC) > 1000/mm^3
- •Platelets > 100,000/mm^3
- •Hemoglobin > 9g/dl
- •Signed, written informed consent
排除标准
- •Primary hepatic dysfunction including known cirrhosis or active hepatitis. Subjects with biliary obstruction must be stented prior to initiating treatment
- •Evidence of clinically significant pancreatitis as determined by the investigator
- •Evidence of significant ascites as determined by investigator
- •Subjects on systemic corticosteroid (>10 mg prednisone per day or equivalent), systemic immunomodulators, or other systemic immunosuppressive drugs
- •Known to be HIV+
- •Pregnant or breast-feeding. Female subjects of childbearing age must have negative serum or urine pregnancy test within 2 weeks of beginning protocol therapy
- •Other current malignancy (except squamous or basal cell skill cancers)
- •Other serious co-morbid illnesses or compromised organ function
- •Known sensitivity or allergic reactions to acyclovir or valacyclovir
结局指标
主要结局
Safety grade by CTCAE version 4.0
时间窗: From the time of CAN-2409 administration to 30 days after the last dose of valacyclovir.
Frequency of adverse events.
Survival Rate
时间窗: 24 months
All eligible subjects will be followed for at least 2 additional years from the completion of primary treatment window.
次要结局
- Overall survival (OS) from time of diagnosis(60 months)
- Progression free survival (PFS) from time of study enrollment(60 months)
- Immunological biomarker characterization in tumor and peripheral blood(24 months)
- Overall survival (OS) from time of study enrollment(60 months)
- Progression free survival (PFS) from time of diagnosis(60 months)
- Resection rate(12 weeks)
- Disease free survival (DFS) in subjects with R0 resection(60 months)