DOVIPA, a Phase II Study Evaluating Efficacy and Safety of DOstarlimab and Oral VItamin D3 with Folinic Acid, 5FU, Irinotecan Plus Oxalipaltin (mFOLFIRINOX) in Non Pretreated Metastatic PAncreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Hopital Foch
- 入组人数
- 35
- 试验地点
- 5
- 主要终点
- Objective response rate (ORR) according to Response Evaluation Criteria version 1.1 (RECIST 1.1) in patients with pancreatic adenocarcinoma and measurable disease
研究概览
简要总结
The goal of this clinical trial is to estimate the antitumor response of mFOLFIRINOX + Dostarlimab + oral HD vitamin D3 in patients with non-pretreated histologically confirmed metastatic Stage IV adenocarcinoma of the pancreas. The patients must have an Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) 0 or 1 and adequate organ functions.
The main objective of the study will be assessed by estimating Objective response rate (ORR) according to Response Evaluation Criteria version 1.1 (RECIST 1.1) in patients with pancreatic adenocarcinoma and measurable disease.
The Secondary objectives are :
- To assess the safety and tolerability of mFOLFIRINOX + Dostarlimab + HD Vitamin D according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 by evaluating the Median Progression Free Survival (mPFS) in months, the Median Overall Survival (mOS) in months, the Median Duration of Response (mDOR) in months and Clinical benefit rate according to RECIST 1.1 (CBR)
- To further evaluate the antitumor efficacy of mFOLFIRINOX + Dostarlimab + oral HD Vitamin D by evaluating the type, frequency, and severity of treatment-emergent adverse events (TEAEs); adverse events of special interest (AESIs); safety laboratory findings There are also exploratory objectives to better understand the pancreatic adenocarcinoma.
Participants will be cared for in the digestive oncology department. A selection review will be carried out to check compliance with the study eligibility criteria. Patients included in the study will be treated with 4 cycles of induction therapy. Each cycle lasts 6weeks and includes chemotherapy such as mFolfirinox D1,D15 and D29, combined with dostarlimab 500 mg every 3 weeks and daily oral vitamin D3.
At the end of the induction treatment period, maintenance treatment will be instituted with LV5FU chemotherapy combined with dostarlimab 1000 mg every 6 weeks and daily oral vitamine D3. Treatment will be maintained until progression or unacceptable toxicity.
Throughout this period, patients will be monitored for their safety. Imaging examinations will also be carried out to monitor the progression of tumour disease.
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 75 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
Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3
Patients will be included and treated according to the following treatment regimen:
- Intra-venous (i.v) dostarlimab: day1 - d21: 500mg IV q3Weeks (cycle 1 to cycle 4) then 1000 mg IV q6Weeks (from cycle 5 onwards)
- Oral vitamin D3 8000 IU/d for 14 days, then 4000IU/d
- mFOLFIRINOX d1, d15, d29 is administered as follow: oxaliplatin 85 mg/m2 on day1, IV infusion over 2 h, immediately followed by folinic acid 400 mg/m2 or calcium levofolinate 200 mg/m2 given as a 2-h IV infusion, with the addition of irinotecan 180 mg/m2 as per dose-level given as a 90-min intravenous infusion through a Y-connector immediately followed by 5- fluorouracil 2400 mg/m2 over 46 h continuous infusion (cycle 1 to cycle 4). From cycle 5, the mFolfirinox will be substituted by LV5FU D1, D15 and D29.
干预措施: Dostarlimab (Drug)
Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3
Patients will be included and treated according to the following treatment regimen:
- Intra-venous (i.v) dostarlimab: day1 - d21: 500mg IV q3Weeks (cycle 1 to cycle 4) then 1000 mg IV q6Weeks (from cycle 5 onwards)
- Oral vitamin D3 8000 IU/d for 14 days, then 4000IU/d
- mFOLFIRINOX d1, d15, d29 is administered as follow: oxaliplatin 85 mg/m2 on day1, IV infusion over 2 h, immediately followed by folinic acid 400 mg/m2 or calcium levofolinate 200 mg/m2 given as a 2-h IV infusion, with the addition of irinotecan 180 mg/m2 as per dose-level given as a 90-min intravenous infusion through a Y-connector immediately followed by 5- fluorouracil 2400 mg/m2 over 46 h continuous infusion (cycle 1 to cycle 4). From cycle 5, the mFolfirinox will be substituted by LV5FU D1, D15 and D29.
干预措施: Vitamin D3 (Cholecalciferol) (Drug)
Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3
Patients will be included and treated according to the following treatment regimen:
- Intra-venous (i.v) dostarlimab: day1 - d21: 500mg IV q3Weeks (cycle 1 to cycle 4) then 1000 mg IV q6Weeks (from cycle 5 onwards)
- Oral vitamin D3 8000 IU/d for 14 days, then 4000IU/d
- mFOLFIRINOX d1, d15, d29 is administered as follow: oxaliplatin 85 mg/m2 on day1, IV infusion over 2 h, immediately followed by folinic acid 400 mg/m2 or calcium levofolinate 200 mg/m2 given as a 2-h IV infusion, with the addition of irinotecan 180 mg/m2 as per dose-level given as a 90-min intravenous infusion through a Y-connector immediately followed by 5- fluorouracil 2400 mg/m2 over 46 h continuous infusion (cycle 1 to cycle 4). From cycle 5, the mFolfirinox will be substituted by LV5FU D1, D15 and D29.
干预措施: mFOLFIRINOX Treatment Regimen (Drug)
Combination of mFOLFIRINOX plus dostarlimab and oral vitamin D3
Patients will be included and treated according to the following treatment regimen:
- Intra-venous (i.v) dostarlimab: day1 - d21: 500mg IV q3Weeks (cycle 1 to cycle 4) then 1000 mg IV q6Weeks (from cycle 5 onwards)
- Oral vitamin D3 8000 IU/d for 14 days, then 4000IU/d
- mFOLFIRINOX d1, d15, d29 is administered as follow: oxaliplatin 85 mg/m2 on day1, IV infusion over 2 h, immediately followed by folinic acid 400 mg/m2 or calcium levofolinate 200 mg/m2 given as a 2-h IV infusion, with the addition of irinotecan 180 mg/m2 as per dose-level given as a 90-min intravenous infusion through a Y-connector immediately followed by 5- fluorouracil 2400 mg/m2 over 46 h continuous infusion (cycle 1 to cycle 4). From cycle 5, the mFolfirinox will be substituted by LV5FU D1, D15 and D29.
干预措施: LV5FU2 (Drug)
结局指标
主要结局
Objective response rate (ORR) according to Response Evaluation Criteria version 1.1 (RECIST 1.1) in patients with pancreatic adenocarcinoma and measurable disease
时间窗: 24 months
The proportion of patients with an objective response at the completion of their follow-up (truncated at 24 months), among all eligible patients. An objective response will be defined as the best overall response of complete response (CR) or partial response (PR) assessed by investigators using validated criteria (i.e. RECIST 1.1)
次要结局
- Incidence of treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0.(From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months")
- Median Duration of Response (mDOR) in months(24 months)
- Incidence of participants with adverse events of special interest (AESIs) as assessed by CTCAE v5.0.(From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months")
- Number of Participants With Clinically Significant Changes in Hematology, Clinical Chemistry, Thyroid Function and Urinalysis Lab Parameters(From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months")
- Number of Participants With AEs Leading to Death(From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months")
- Median Progression Free Survival (mPFS) in months(24 months)
- Median Overall Survival (mOS) in months(24 months)
- Number of Participants With Immune Related Adverse Events (irAEs)(From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months")
- Clinical benefit rate according to RECIST 1.1 (CBR)(24 months)
- Number of Participants With Adverse Events Leading to Discontinuation(From the initiation of study treatment until 90 days after the last dose or 30 days following cessation of study intervention if the participant initiates new anticancer therapy, whichever is earlier, assessed up to 24 months")
- Incidence of patient premature discontinuations (due to SAE or non-adherence to protocol)(From the initiation of study treatment until premature discontinuation due to serious adverse event or non adherence to protocol whichever is earlier, assessed up to 24 months")
- Incidence of dose modifications(From the initiation of study treatment until the last dose administration, assessed up to 24 months")
- Incidence of delays or interruptions in the administration of treatment due to the appearance of AEs(From the initiation of study treatment until the last dose administration, assessed up to 24 months")