Pilot Study Evaluating Allogeneic GM-CSF-Transduced Pancreatic Tumor Cell Vaccine (GVAX) and Low Dose Cyclophosphamide With Fractionated Stereotactic Body Radiation Therapy (SBRT) and FOLFIRINOX Chemotherapy in Patients With Resected Adenocarcinoma of the Pancreas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicities
研究概览
简要总结
The purpose of this study is to estimate safety of GVAX Pancreas Vaccine (GVAX) with immune modulating doses of cyclophosphamide (Cy) followed by SBRT and FOLFIRINOX chemotherapy in pancreatic cancer patients after surgery.
详细描述
This study enrolled patients with surgically resected adenocarcinoma of the pancreas who had titanium clips placed at the time of surgery in order to guide SBRT treatment.
Enrollment was based on traditional 3+3 design with grade 3-4 diarrhea and/or neutropenia defined as the dose limiting toxicity (DLT) within the first 2 cycles (8 weeks) of FOLFIRINOX. The first group of 3 patients (Cohort 1) received SBRT and full dose FOLFIRINOX. The second group of 4 patients (Cohort 2) received SBRT and modified FOLFIRINOX, and the third group of 12 patients (Cohort 3) received SBRT and modified FOLFIRINOX as well as Cy/GVAX vaccinations.
Cy/GVAX (patients 8-19): cyclophosphamide (Cy) at 200 mg/m^2 intravenously over 30 minutes the day before each vaccine. Each vaccination (GVAX) consists of six total intradermal injections of vaccine, two each in the upper right and left thighs, and two in the upper non-dominant arm. Each injection consists of approximately 2.5x10^8 cells of each cell line (PANC 6.03/PANC 10.05) for a total of 5x10^8 cells. The first dose of Cy/GVAX was given within 6-10 weeks from surgery.
Adjuvant SBRT was given 13-17 days after the first dose of Cy/GVAX. Patients receive 5 days of SBRT (6.6 gray (Gy) daily for 33 Gy total) to the tumor bed as delineated by surgical clips placed by the surgeon.
Six 28-day cycles of FOLFIRINOX, starting at least one week after completion of SBRT.
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 76 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1: SBRT and FOLFIRINOX
The initial 3 patients were treated with SBRT and full dose FOLFIRINOX and observed for the first 2 cycles (8 weeks) for dose limiting toxicities (DLTs). If 2-3 patients are observed with uncontrolled grade 3-4 diarrhea, 2-3 patients are observed with grade 3-4 thrombocytopenia, or if 3 patients are observed with grade 3-4 neutropenia within the first 2 cycles of FOLFIRINOX administration (8 weeks) then the dose level will be deemed unacceptable.
干预措施: Stereotactic Body Radiation (Radiation)
Cohort 1: SBRT and FOLFIRINOX
The initial 3 patients were treated with SBRT and full dose FOLFIRINOX and observed for the first 2 cycles (8 weeks) for dose limiting toxicities (DLTs). If 2-3 patients are observed with uncontrolled grade 3-4 diarrhea, 2-3 patients are observed with grade 3-4 thrombocytopenia, or if 3 patients are observed with grade 3-4 neutropenia within the first 2 cycles of FOLFIRINOX administration (8 weeks) then the dose level will be deemed unacceptable.
干预措施: FOLFIRINOX (Drug)
Cohort 2: SBRT and modified FOLFIRINOX
The next 4 patients were treated with SBRT and modified FOLFIRINOX and observed for the first 2 cycles (8 weeks) for dose limiting toxicities (DLTs). If no patients are observed with grade 3-4 diarrhea, thrombocytopenia, or neutropenia, then the next cohort of patients will receive SBRT, modified FOLFIRINOX, and GVAX (with Cy).
干预措施: Stereotactic Body Radiation (Radiation)
Cohort 2: SBRT and modified FOLFIRINOX
The next 4 patients were treated with SBRT and modified FOLFIRINOX and observed for the first 2 cycles (8 weeks) for dose limiting toxicities (DLTs). If no patients are observed with grade 3-4 diarrhea, thrombocytopenia, or neutropenia, then the next cohort of patients will receive SBRT, modified FOLFIRINOX, and GVAX (with Cy).
干预措施: FOLFIRINOX (Drug)
Cohort 3: CY, GVAX, SBRT, and modified FOLFIRINOX
The last 12 patients will receive Cy, GVAX, SBRT, and modified FOLFIRINOX.
干预措施: Cyclophosphamide (Drug)
Cohort 3: CY, GVAX, SBRT, and modified FOLFIRINOX
The last 12 patients will receive Cy, GVAX, SBRT, and modified FOLFIRINOX.
干预措施: GVAX Pancreas Vaccine (Biological)
Cohort 3: CY, GVAX, SBRT, and modified FOLFIRINOX
The last 12 patients will receive Cy, GVAX, SBRT, and modified FOLFIRINOX.
干预措施: Stereotactic Body Radiation (Radiation)
Cohort 3: CY, GVAX, SBRT, and modified FOLFIRINOX
The last 12 patients will receive Cy, GVAX, SBRT, and modified FOLFIRINOX.
干预措施: FOLFIRINOX (Drug)
结局指标
主要结局
Dose Limiting Toxicities
时间窗: 8 weeks
The number of participants experiencing grade 3-4 diarrhea, neutropenia, and thrombocytopenia within the first 2 cycles (8 weeks) of treatment, regardless of attribution. The rates of each of these toxicities were considered unacceptable if they were 40%, 60%, and 40%, respectively. A decision rule similar to the traditional 3+3 design was used to determine whether it was safe to continue on to the next cohort.
Grade 3 or Higher Cy/GVAX-related Adverse Events
时间窗: 116 months
Number of participants with grade 3 or above adverse event attributed to Cy or the GVAX pancreas vaccine. Each adverse event (as defined by NCI CTCAE v4.0) was counted only once for a given subject.
次要结局
- Overall Survival (OS)(96 months)
- Freedom From Local Progression (FFLP)(96 months)
- Disease-free Survival (DFS)(96 months)
- Distant Metastases Free Survival (DMFS)(96 months)