Adjuvant Versus Neoadjuvant Plus Adjuvant Chemotherapy In Resectable Pancreatic Cancer

Study Overview

Adjuvant Versus Neoadjuvant Plus Adjuvant Chemotherapy in Resectable Pancreatic Cancer

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. * Trial with medicinal product

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.

Pancreatic Cancer

DRUG: Neoadjuvant Chemotherapy with gemcitabine/oxaliplatin
DRUG: adjuvant chemotherapy with gemcitabine

NEOPAC

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2010-09-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2019-07-24
First Submitted that Met QC Criteria 2011-03-10	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2019-07-25
First Posted (ACTUAL) 2011-03-14	Results First Posted N/A	Last Verified 2019-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: neoadjuvant + adjuvant chemotherapy neoadjuvant chemotherapy is based on gemcitabine/oxaliplatin adjuvant therapy is based on gemcitabine	DRUG: Neoadjuvant Chemotherapy with gemcitabine/oxaliplatin 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. Thereafter, surgery is performed if the
ACTIVE_COMPARATOR: adjuvant chemotherapy adjuvant therapy is based on gemcitabine	DRUG: Neoadjuvant Chemotherapy with gemcitabine/oxaliplatin 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. Thereafter, surgery is performed if the DRUG: adjuvant chemotherapy with gemcitabine Patients randomized to arm B undergo surgery and receive the same adjuvant treatment as in arm A.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: neoadjuvant + adjuvant chemotherapy

neoadjuvant chemotherapy is based on gemcitabine/oxaliplatin adjuvant therapy is based on gemcitabine

DRUG: Neoadjuvant Chemotherapy with gemcitabine/oxaliplatin

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. Thereafter, surgery is performed if the

ACTIVE_COMPARATOR: adjuvant chemotherapy

adjuvant therapy is based on gemcitabine

DRUG: Neoadjuvant Chemotherapy with gemcitabine/oxaliplatin

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. Thereafter, surgery is performed if the

DRUG: adjuvant chemotherapy with gemcitabine

Patients randomized to arm B undergo surgery and receive the same adjuvant treatment as in arm A.

Primary Outcome Measures	Measure Description	Time Frame
Progression-free survival	by computed tomography	9 months after inclusion

Secondary Outcome Measures	Measure Description	Time Frame
Progression-free survival	by computer tomography	12, 15, 21, 27, 33, 39, ... months after inclusion
histological response	Histology	Pancreatic resection
overall survival		1, 3 and 5 years after inclusion
complication rates after surgery		60 days postoperative
feasibility of adjuvant chemotherapy		within 8 postoperative weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

resectable adenocarcinoma of the pancreatic head (requiring duodeno-pancreatectomy)
T1-3, Nx, M0 (UICC 6th version, 2002)
infiltration of the portal vein (<180°) is not an exclusion criterion
cytologic or histologic confirmation of adenocarcinoma
age >18 years
written informed consent

contraindication for Whipple procedure
an infiltration >180° of the portal vein
abutment of the tumor to the superior mesenteric artery
infiltration of the superior mesenteric artery or the celiac trunk
chronic neuropathy > grade 2
WHO performance score >2
uncorrectable cholestasis (bilirubin > 100mmol/l despite drainage attempts for more than four weeks prior to inclusion)
female patients in child bearing age not using adequate contraception (oral or subcutaneous contraceptives, intrauterine pessary (IUP), condoms)
pregnant or lactating women
mental or organic disorders which could interfere with giving informed consent or receiving treatments
Second malignancy diagnosed within the past 5 years, except non-melanomatous skin cancer or non-invasive cervical cancer
percutaneous biopsy of the primary tumor

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Pierre-Alain Clavien, MD, PhD, UniversitaetsSpital Zuerich

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Heinrich S, Pestalozzi B, Lesurtel M, Berrevoet F, Laurent S, Delpero JR, Raoul JL, Bachellier P, Dufour P, Moehler M, Weber A, Lang H, Rogiers X, Clavien PA. Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study). BMC Cancer. 2011 Aug 10;11:346. doi: 10.1186/1471-2407-11-346.

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Clinical Trial Record