Neoadjuvant Treatment vs Upfront Surgery for Left Sided Pancreatic Cancer (LEFT-PANC) - a Study Protocol for a Prospective Randomized Multicenter Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 381
- 试验地点
- 2
- 主要终点
- Overall Survival
研究概览
简要总结
Pancreatic cancer is one of the most treatment resistant malignancies, often diagnosed at a late stage and associated with poor survival. The 5-year overall survival rate remains around 10%. Prognosis is affected by multiple factors including tumor stage, biology, treatment response, and anatomical location. Distal (left-sided) pancreatic cancer, originating from the body or tail of the pancreas, accounts for approximately 20-25% of all pancreatic cancers and has been associated with worse survival than pancreatic head cancer, even when adjusted for stage. This may be due to histological, molecular, and embryological differences, and varied systemic therapy responses.
Neoadjuvant chemotherapy has become increasingly important in managing pancreatic cancer. It may improve outcomes by reducing tumor size, allowing for more complete (R0) resections, treating micrometastatic disease early, and identifying patients unlikely to benefit from surgery. While neoadjuvant therapy is recommended for borderline resectable and locally advanced tumors, randomized trials have not shown benefit for patients with upfront resectable pancreatic head cancer. Importantly, no randomized controlled trials have investigated the benefit of neoadjuvant treatment specifically in patients with upfront resectable left-sided pancreatic cancer, despite its distinct biology and worse prognosis.
Retrospective data suggest neoadjuvant therapy may improve survival in left-sided tumors. A recent multicenter study reported significantly longer overall survival in patients treated with neoadjuvant therapy compared to upfront surgery alone. However, prospective randomized data are lacking.
This multicenter randomized trial aims to assess whether patients with resectable left-sided pancreatic cancer benefit from neoadjuvant chemotherapy compared to upfront surgery. The study will reflect real-world clinical practice by allowing both commonly used regimens-FOLFIRINOX and Gemcitaine-Nab-paclitaxel -as neoadjuvant options. Previous studies have shown these regimens to be similarly effective, and switching between them due to toxicity or progression is feasible and does not seem to impair surgical outcomes or survival. This study aims to evaluate the benefits of neoadjuvant chemotherapy before surgery in a prospective multicenter randomized setting for resectable left-sided pancreatic cancer patients.
详细描述
This is a multicenter, open-label, randomized phase III trial evaluating whether neoadjuvant chemotherapy improves overall survival in patients with resectable left-sided (body/tail) pancreatic cancer compared to the current standard of upfront surgery followed by adjuvant chemotherapy.
Eligible patients have histologically confirmed pancreatic adenocarcinoma located in the body or tail of the pancreas, ECOG/WHO performance status 0-2, and radiologically resectable disease according to NCCN criteria. Patients are randomized 1:1 to receive either:
- neoadjuvant chemotherapy, followed by surgery and adjuvant therapy, or
- upfront surgery followed by adjuvant chemotherapy.
Randomization uses a minimization method with stratification by performance status, CA19-9 level, treatment center, and chemotherapy regimen. Surgery is scheduled within 4-6 weeks of randomization (control arm) or after the last neoadjuvant cycle (intervention arm). Left pancreatectomy (open or minimally invasive) with standard lymphadenectomy and splenectomy is performed with complications reported using Dindo/Clavien classification and ISGPS criteria. Radical antegrade posterior pancreatosplenectomy may be performed when needed to ensure clear margins. Tumor response to neoadjuvant therapy will be evaluated by standardized histopathological grading.
Patients are followed with laboratory tests and CT imaging at the completion of adjuvant therapy and every six months thereafter until disease recurrence or up to five years after surgery. Quality of life is assessed at baseline, pre-surgery (in the neoadjuvant arm), 4 weeks post-op, and during follow-up using the EORTC QLQ-C30 and PAN26 instruments. Patients are followed for recurrence and survival every 6 months for up to 5 years. Safety is monitored per CTCAE v5.0, with SAEs and SUSARs reported per regulatory guidelines. An independent DSMB will review safety data. Blood and tumor samples will be stored for future translational research.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Resectable left pancreatic cancer according to NCCN criteria
- •Written and informed consent
- •Age > 18y
- •Fit for surgery
- •Fit for neoadjuvant chemotherapy
排除标准
- •ECOG > 2
- •Histology other than ductal adenocarcinoma
- •Unable to give written consent
研究组 & 干预措施
Perioperative chemotherapy
Patients who undergo surgical resection will receive adjuvant chemotherapy with 4 cycles (2 months) of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and 5-fluorouracil (400 mg/m2 bolus then 2400 mg/m2 over 46 h)) OR 2 cycles (2 months) of Gemcitabine 1000 mg/m2 over 30 min at day 1, 8, 15 of each 28-day cycle and capecitabine 830 mg/m2 ×2 daily for 3 weeks and one week rest of each 28-day cycle. Regimen changes due to toxicity are allowed.
After 2 and 4 months of NAT, response imaging (multiphased body CT) is assessed at a local pancreatic MDT. If stable disease or regression is observed, patients will undergo surgery after chemotherapy break of 3-6 weeks. Adjuvant chemotherapy (2-4 months) must be started within 4-12 weeks after resection. Dose adjustments follow local practice; adjuvant therapy depends on patient condition (mFOLFIRINOX, Gem+capecitabine, or gemcitabine alone).
干预措施: mFOLFIRINOX neoadjuvant chemotherapy / Nab-paclitaxel and gemcitabine (Drug)
结局指标
主要结局
Overall Survival
时间窗: From randomization until death or study completion, up to approximately 5 years.
Overall survival of participants, defined as the time from randomization until death from any cause, analyzed in the intention-to-treat (ITT) population.
次要结局
未报告次要终点
研究者
Hanna Seppänen
Principal Investigator, Adjunct Professor, Pancreatic surgeon
Helsinki University Central Hospital