Preoperative Treatment With mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose Stereotactic Body Radiation Therapy (iHD-SBRT) for Borderline Resectable Pancreatic Adenocarcinoma: a Randomised Phase II Study (STEREOPAC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 256
- 试验地点
- 10
- 主要终点
- R0 Resection rate
研究概览
简要总结
Surgical resection is the only potentially curative treatment for patients with pancreatic cancer with the aim of curative R0 resection and related improvement of survival. As a standard, surgery is usually followed by adjuvant therapy that improves survival but neoadjuvant therapy (NAT) is a rapidly emerging concept that needs to be explored and validated in terms of therapeutic options in borderline resectable pancreatic tumors. In this setting, preoperative FFX seems to be feasible and can be prolonged by radiation therapy. However, the exact and best therapeutic sequence is not yet known and the additional role of adding isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) to chemotherapy requires validation in randomised trials. We propose to evaluate the impact and efficacy of adding iHD-SBRT to preoperative neoadjuvant mFFX or Gem-NabP in patients with borderline resectable pancreatic adenocarcinoma.
详细描述
STEREOPAC is an multicenter, academic, prospective, randomised comparative, interventional study.
Patients receive 4 cycles of mFOLFIRINOX (or Gem-Nab-P)*. A full restaging (clinical, morphologic imaging, vascular involvement, biologics, CA 19.9) is performed. Non-progressive patients will be randomised (1:1) to
ARM A for receiving 4 additional cycles of chemo followed by surgery.
or to
ARM B for receiving 5th and 6th cycles of chemo then iHD-SBRT followed by a 7th (and optional 8th cycle) followed by surgery.
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
- 未提供
排除标准
- •Evidence of extrapancreatic disease on diagnostic imaging (CT, MRI or PET scan), histologically proven or at laparoscopy, including distal nodal involvement beyond the peripancreatic tissues (including non-regional lymph node involvement, ie: proven involvement of precaval lumbar lymphadenopathy(ies) and/or distant metastases
- •Locally advanced disease as defined by the NCCN criteria (version 2.2021) ie > 180° arterial encasement (SMA and CA) unreconstructible venous encasement (SMV/PV) due to tumor involvement or occlusion of a long segment.
- •CA 19.9 > 2500 kU/l (baseline and absence of cholestasis)
- •Contraindication of surgery (general)
- •Contraindications to receive FFX or gemcitabine-nab-Paclitaxel
- •History of radiotherapy of the upper abdomen
- •Prior treatment with oxaliplatin, irinotecan, fluoruouracil or capecitabin
- •Patient < 18 years old
- •Major surgery within 4 weeks of study entry
- •Uncontrolled pre-existing disease including, but not limited to: active infection, symptomatic congestive heart failure, unstable angina, social / psychiatric disorder that would limit compliance to treatment and good understanding of the informed consent form
- •Other concurrent anticancer therapies
- •Existence of another active neoplasia other than basal cell carcinoma of the skin, cervical carcinoma in situ or non-metastatic prostate cancer. Patients who have a history of neoplasia must have been in remission for more than 5 years to be included in the protocol
- •Pregnant or breastfeeding women; for women of childbearing potential only, a negative pregnancy test done < 7 days prior to registration is required. Using of reliable contraception for at least 1 month before treatment is mandatory
- •Chronic concomitant treatment with strong inhibitors of cytochrome p450, family 3, subfamily a, polypeptide 4 gene (CYP3A4) is not allowed on this study; patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study
- •Additional exclusion criteria before randomisation:
- •Progressive disease (RECIST or PETCT, including non locoregional nodal involvement and increase of CA 19.9 by 20%) after receiving 4 cycles of FFX (or G/NP), including shift chemotherapy in case of early progression.
- •CA 19.9 > 1000 kU/l after neoadjuvant therapy.
- •Presence of unmanageable toxicity during the first part of neoadjuvant chemotherapy (first 4 cycles or 6 doses of FFX or G/NP, respectively.
- •Pancreatic tumour > 7.0 cm in greatest axial dimension at the time of randomization
- •Massive invasion of the stomach or intestines and/or direct intestinal invasion of the mucosae visible at ultrasoundendoscopy
- •Active gastric or duodenal ulcer disease at the time of randomization. Tolerated in case of antecedent without active ulcer (confirmation by endoscopy before iHD-SBRT)
研究组 & 干预措施
Arm A
mFOLFIRINOX (oxaliplatin: 85 mg/m2, CPT-11: 165-180 mg/m2, folinic acid: 400mg/m2 and 5FU 2000-2400 mg/m2/46 h) regimen for 8 cycles every 2 weeks; or*Gemcitabine-Nab-P: gem: 1000 mg/m2 weekly 3 w/4; nab-P: 125 mg/m2 3 w/4 for 4 cycles in case of unfit for mFFX).
干预措施: mFOLFIRINOX or Gemcitabine nab-paclitaxel (Drug)
Arm A
mFOLFIRINOX (oxaliplatin: 85 mg/m2, CPT-11: 165-180 mg/m2, folinic acid: 400mg/m2 and 5FU 2000-2400 mg/m2/46 h) regimen for 8 cycles every 2 weeks; or*Gemcitabine-Nab-P: gem: 1000 mg/m2 weekly 3 w/4; nab-P: 125 mg/m2 3 w/4 for 4 cycles in case of unfit for mFFX).
干预措施: Surgery (Procedure)
Arm B
mFOLFIRINOX for 6 cycles (or for 3 cycles Gemcitabine-Nab-P: gem: 1000 mg/m2 weekly 3 w/4; nab-P: 125 mg/m2 3 w/4 in case of unfit for mFFX) +Isotoxic high-dose SBRT: 5 x 7Gy with Simultaneous Integrated Boost (SIB) up to maximum 55Gy (= 1 week; starting ideally 2 weeks and maximum within 4 weeks after the end of chemotherapy)
干预措施: mFOLFIRINOX or Gemcitabine nab-paclitaxel (Drug)
Arm B
mFOLFIRINOX for 6 cycles (or for 3 cycles Gemcitabine-Nab-P: gem: 1000 mg/m2 weekly 3 w/4; nab-P: 125 mg/m2 3 w/4 in case of unfit for mFFX) +Isotoxic high-dose SBRT: 5 x 7Gy with Simultaneous Integrated Boost (SIB) up to maximum 55Gy (= 1 week; starting ideally 2 weeks and maximum within 4 weeks after the end of chemotherapy)
干预措施: Isotoxic High-Dose (iHD)-SBRT (Radiation)
Arm B
mFOLFIRINOX for 6 cycles (or for 3 cycles Gemcitabine-Nab-P: gem: 1000 mg/m2 weekly 3 w/4; nab-P: 125 mg/m2 3 w/4 in case of unfit for mFFX) +Isotoxic high-dose SBRT: 5 x 7Gy with Simultaneous Integrated Boost (SIB) up to maximum 55Gy (= 1 week; starting ideally 2 weeks and maximum within 4 weeks after the end of chemotherapy)
干预措施: Surgery (Procedure)
结局指标
主要结局
R0 Resection rate
时间窗: up to 12 months
Defined as the proportion of eligible randomised patients in whom a R0 resection was achieved during surgery after neoadjuvant treatment with FOLFIRINOX +/- iHD-SBRT. R0 resection indicates a microscopically margin-negative resection (\>1 mm) from the inked margins (pancreatic transection, vascular and posterior circumferential resection margins).
Disease free survival
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 weeks
Defined as time from randomisation to the first documentation of event where events considered are 1) disease progression, per RECIST, prior to surgery, 2) discovery of hepatic or peritoneal carcinomatosis during surgical exploration, 3) recurrent disease following R0-R1 surgery, or 4) death due to any cause.
次要结局
- Locoregional failure free interval (LFFI)(defined as the time interval between the randomisation and the 1st documented date of locoregional failure, assessed up to 60 months)
- Distant metastases free interval (DMFI)(defined as the period of time without distant metastasis after randomisation, assessed up to 60 months)
- Toxicity, Incidence of adverse events(up to 24 months)
- Overall survival (OS)(Defined as the time interval between randomisation and death, assessed up to 60 months)
- Resection rate(up to 12 months)
- Pathologic complete/major response (pCR)(up to 12 months)
- Complete feasibility of the therapeutic sequence(up to 12 months)
- Postoperative complications(up to 12 months)
- Quality of life (QoL) assessment - General(up to 24 months)
- Quality of life (QoL) assessment - Pancreatic cancer(up to 24 months)
- Quality of life (QoL) assessment - Depression(up to 24 months)
- Technical and quality success rate of EUS-delivered fiducials.(up to 12 months)