Adjuvant Versus Neoadjuvant Plus Adjuvant Chemotherapy in Resectable Pancreatic Cancer

This study is currently recruiting participants.
Verified March 2011 by University of Zurich
Sponsor:
Information provided by:
University of Zurich
ClinicalTrials.gov Identifier:
NCT01314027
First received: September 29, 2010
Last updated: March 10, 2011
Last verified: March 2011
  Purpose

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

Condition Intervention Phase
Pancreatic Cancer
Drug: Neoadjuvant Chemotherapy with gemcitabine/oxaliplatin
Drug: adjuvant chemotherapy with gemcitabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adjuvant Gemcitabine Versus NEOadjuvant Gemcitabine/Oxaliplatin Plus Adjuvant Gemcitabine in Resectable PAncreatic Cancer: a Randomized Multicenter Phase III Study (NEOPAC Study)

Resource links provided by NLM:


Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 9 months after inclusion ] [ Designated as safety issue: Yes ]
    by computed tomography


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 12, 15, 21, 27, 33, 39, ... months after inclusion ] [ Designated as safety issue: Yes ]
    by computer tomography

  • histological response [ Time Frame: Pancreatic resection ] [ Designated as safety issue: No ]
    Histology

  • overall survival [ Time Frame: 1, 3 and 5 years after inclusion ] [ Designated as safety issue: No ]
  • complication rates after surgery [ Time Frame: 60 days postoperative ] [ Designated as safety issue: Yes ]
  • feasibility of adjuvant chemotherapy [ Time Frame: within 8 postoperative weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 310
Study Start Date: September 2009
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 restaging does not reveal a contraindication. Finally, all patients receive adjuvant gemcitabine for six months.

Other Names:
  • gemcitabine
  • eloxatin
Active Comparator: adjuvant chemotherapy
adjuvant therapy is based on gemcitabine
Drug: adjuvant chemotherapy with gemcitabine
Patients randomized to arm B undergo surgery and receive the same adjuvant treatment as in arm A.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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

Exclusion criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01314027

Contacts
Contact: Pierre-Alain Clavien, MD, PhD +41 44 255 3300 clavien@access.unizh.ch

Locations
Belgium
University Hospital of Gent Not yet recruiting
Gent, Belgium
Contact: Frederick Berrevoet, MD         
France
University Hospital of Marseille Not yet recruiting
Marseille, France
Contact: Jean-Robert Delpero, MD         
University Hospital of Strasbourg Not yet recruiting
Strasbourg, France
Contact: Philippe Bachellier, MD         
Germany
University Hospital Mainz Not yet recruiting
Mainz, Germany, 55131
Contact: Stefan Heinrich, MD    0049 6131 17 2738    stefan.heinrich@unimedizin-mainz.de   
Sub-Investigator: Stefan Heinrich, MD         
Switzerland
University Hospital of Zurich Recruiting
Zurich, Switzerland
Contact: Pierre-Alain Clavien, MD, PhD    0041 44 255 3300    clavien@access.unizh.ch   
Sub-Investigator: Mickael Lesurtel, MD         
Sub-Investigator: Bernhard Pestalozzi, MD         
Sub-Investigator: Stefan Heinrich, MD         
Sponsors and Collaborators
University of Zurich
Investigators
Study Director: Pierre-Alain Clavien, MD, PhD UniversitaetsSpital Zuerich
  More Information

No publications provided by University of Zurich

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Clavien Pierre-Alain, Prof. Dr., VIS Klinik f. Viszeralchirurgie
ClinicalTrials.gov Identifier: NCT01314027     History of Changes
Other Study ID Numbers: NEOPAC
Study First Received: September 29, 2010
Last Updated: March 10, 2011
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on April 16, 2014