Adjuvant Gemcitabine Versus NEOadjuvant Gemcitabine/Oxaliplatin Plus Adjuvant Gemcitabine in Resectable PAncreatic Cancer: a Randomized Multicenter Phase III Study (NEOPAC Study)
Adjuvant Gemcitabine Versus NEOadjuvant Gemcitabine/Oxaliplatin Plus Adjuvant Gemcitabine in Resectable PAncreatic Cancer: a Randomized Multicenter Phase III Study (NEOPAC Study)
The outcome of patients with resected pancreatic cancer has significantly been improved by adjuvant chemotherapy. However, a large proportion of patients cannot receive adjuvant chemotherapy due to surgical complications. Neoadjuvant chemotherapy has been shown to be safe and effective and can be applied to all patients. This study should test neoadjuvant chemotherapy in a randomized manner.
Patients with resectable cytologically proven adenocarinoma of the pancreatic head are randomized to arm A or B.
Patients randomized to arm A receive an 8-week neoadjuvant chemotherapy with gemcitabine/oxaliplatin followed by surgery. Thereafter, all patients receive adjuvant gemcitabine for six months.
Patients randomized to arm B undergo surgery and receive the same adjuvant treatment as in arm A.
The primary study-endpoint is the recurrence-free survival. Tumor recurrence are determined by computed tomography in a defined protocol.
Due to the improvement in the recurrence-free and overall survival by adjuvant chemotherapy, surgery followed by adjuvant chemotherapy is currently considered the standard treatment for resectable pancreatic cancer. However, a significant proportion (>25%) of patients cannot receive adjuvant treatment due to the morbidity of pancreas surgery. Neoadjuvant (preoperative) chemotherapy appears particularly attractive since it can be applied to all patients and has resulted in a significant histological tumor response with a median survival superior to adjuvant chemotherapy in a recent prospective phase II trial.
The aim of this study is to determine the role of neoadjuvant chemotherapy in patients with resectable pancreatic cancer.Eligible patients are randomized to:
arm A: neoadjuvant chemotherapy + resection + adjuvant chemotherapy arm B: resection + adjuvant chemotherapy Neoadjuvant chemotherapy consists of gemcitabine (1000mg/m2) and oxaliplatin (100mg/m2) on days 1, 15, 29 and 43, while adjuvant chemotherapy is based on gemcitabine 1000mg/m2 for 6 months.
If the restaging protocol excludes distant metastases, a diagnostic laparoscopy is performed, followed by a Whipple operation in the absence of distant metastases.
The primary study end-point is the recurrence-free survival after study inclusion, and this is defined by the interval between the date of written informed consent until recurrence. Secondary end-points are the overall survival and the surgical complication rate. Interim analyses are performed after the inclusion of 100 and 200 patients without interrupting patient accrual. An independent data monitoring committee will review the results of each interim analysis and will decide about the study cessation or continuation.
Patients will be followed-up according to the protocol below in order to assess tumor recurrence.
Quality of life will be assessed by the QLQ-30 questionnaire of the EORTC at study entry, after neoadjuvant chemotherapy, start and end of the adjuvant chemotherapy and at each follow-up study visit. Representative histological samples are reviewed and stored by the reference pathologist at the University Hospital of Zurich. These samples will also be used to determine the histological response and extent of cytopathic effects. Furthermore, the nutritional status is assessed from all patients by the prealbumin serum levels at study entry and prior to surgery. Further translational research is desired and will be individually organized by each center.
Inclusion criteria:
Exclusion criteria: