Neo-adjuvant FOLF(IRIN)OX For Resectable Pancreatic Adenocarcinoma

Study Overview

Neo-adjuvant FOLF(IRIN)OX for Resectable Pancreatic Adenocarcinoma

In patients with resectable pancreatic duct adenocarcinoma (PDAC), curative surgery followed by adjuvant chemotherapy is currently the standard of care. However, the long-term results are still poor, with median disease-free and overall survival of 14 months and 23 months. The corresponding 5-year overall survival rate is 20%. Chemotherapy before surgery (neoadjuvant chemotherapy) allows identification of patients with rapidly progressive metastatic disease at time of preoperative restaging (surgery is then avoided in these patients), and may increase the rate of free margin resection (R0) and reduce the risk of local recurrence. Even though single-agent gemcitabine and 5-FU have been validated in adjuvant and metastatic settings, the objective response was low (at around 10%), whereas combination chemotherapy exceeds a response rate of 30% in advanced disease. In metastatic PDAC, palliative FOLFIRINOX chemotherapy has been demonstrated to be effective (in terms of response rates and progression-free survival) and well tolerated. Interestingly, the response rate is increased by using more than two chemotherapeutic agents in advanced pancreatic cancer, justifying the use of an alternative neoadjuvant FOLFOX-based chemotherapy arm. PANACHE-01 is an open, non-comparative, randomised, multicentre Phase II study designed to assess the safety and efficacy of two modes of neo-adjuvant chemotherapy (FOLFIRINOX & FOLFOX) relative to the current reference treatment (surgery and then adjuvant chemotherapy) for resectable PDAC. Patients with immediately resectable PDAC (definition based on the NCCN's (American National Comprehensive Cancer Network 2014) latest guidelines) will be randomised to either pancreatectomy and adjuvant chemotherapy or 4 cycles of neoadjuvant chemotherapy with either FOLFOX or FOLFIRINOX. The patients in the neoadjuvant chemotherapy arms will receive postoperative chemotherapy for 4 months (8 cycles).

N/A

Resectable Pancreatic Duct Adenocarcinoma

DRUG: FOLFOX neoadjuvant chemotherapy
DRUG: FOLFIRINOX neoadjuvant chemotherapy
PROCEDURE: curative surgery for resectable pancreatic duct adenocarcinoma
DRUG: Standard adjuvant chemotherapy
DRUG: adjuvant chemotherapy

2014/210/HP

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 2016-11-03	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2018-04-24
First Submitted that Met QC Criteria 2016-11-07	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2018-04-26
First Posted (ACTUAL) 2016-11-09	Results First Posted N/A	Last Verified 2018-04

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: FOLFOX neoadjuvant chemotherapy 4 cycles of FOLFOX neoadjuvant chemotherapy are administrated to patient. Curative surgery for resectable pancreatic duct adenocarcinoma will be done after neoadjuvant chemotherapy. 8 cycles of adjuvant chemotherapy are administrated following the surgery	DRUG: FOLFOX neoadjuvant chemotherapy 4 cycles of FOLFOX neoadjuvant chemotherapy are administrated to patient PROCEDURE: curative surgery for resectable pancreatic duct adenocarcinoma curative surgery for resectable pancreatic duct adenocarcinoma DRUG: adjuvant chemotherapy 8 cycles of standard adjuvant chemotherapy are administrated
EXPERIMENTAL: FOLFIRINOX neoadjuvant chemotherapy 4 cycles of FOLFIRINOX neoadjuvant chemotherapy are administrated to patient. Curative surgery for resectable pancreatic duct adenocarcinoma will be done after neoadjuvant chemotherapy. 8 cycles of adjuvant chemotherapy are administrated following the sur	DRUG: FOLFIRINOX neoadjuvant chemotherapy 4 cycles of FOLFIRINOX neoadjuvant chemotherapy are administrated to patient PROCEDURE: curative surgery for resectable pancreatic duct adenocarcinoma curative surgery for resectable pancreatic duct adenocarcinoma DRUG: adjuvant chemotherapy 8 cycles of standard adjuvant chemotherapy are administrated
ACTIVE_COMPARATOR: standard adjuvant chemotherapy Curative surgery for resectable pancreatic duct adenocarcinoma will be done after randomization. 12 cycles of standard adjuvant chemotherapy are administrated following the surgery	PROCEDURE: curative surgery for resectable pancreatic duct adenocarcinoma curative surgery for resectable pancreatic duct adenocarcinoma DRUG: Standard adjuvant chemotherapy 12 cycles of standard adjuvant chemotherapy are administrated

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: FOLFOX neoadjuvant chemotherapy

4 cycles of FOLFOX neoadjuvant chemotherapy are administrated to patient. Curative surgery for resectable pancreatic duct adenocarcinoma will be done after neoadjuvant chemotherapy. 8 cycles of adjuvant chemotherapy are administrated following the surgery

DRUG: FOLFOX neoadjuvant chemotherapy

4 cycles of FOLFOX neoadjuvant chemotherapy are administrated to patient

PROCEDURE: curative surgery for resectable pancreatic duct adenocarcinoma

curative surgery for resectable pancreatic duct adenocarcinoma

DRUG: adjuvant chemotherapy

8 cycles of standard adjuvant chemotherapy are administrated

EXPERIMENTAL: FOLFIRINOX neoadjuvant chemotherapy

4 cycles of FOLFIRINOX neoadjuvant chemotherapy are administrated to patient. Curative surgery for resectable pancreatic duct adenocarcinoma will be done after neoadjuvant chemotherapy. 8 cycles of adjuvant chemotherapy are administrated following the sur

DRUG: FOLFIRINOX neoadjuvant chemotherapy

4 cycles of FOLFIRINOX neoadjuvant chemotherapy are administrated to patient

PROCEDURE: curative surgery for resectable pancreatic duct adenocarcinoma

curative surgery for resectable pancreatic duct adenocarcinoma

DRUG: adjuvant chemotherapy

8 cycles of standard adjuvant chemotherapy are administrated

ACTIVE_COMPARATOR: standard adjuvant chemotherapy

Curative surgery for resectable pancreatic duct adenocarcinoma will be done after randomization. 12 cycles of standard adjuvant chemotherapy are administrated following the surgery

PROCEDURE: curative surgery for resectable pancreatic duct adenocarcinoma

curative surgery for resectable pancreatic duct adenocarcinoma

DRUG: Standard adjuvant chemotherapy

12 cycles of standard adjuvant chemotherapy are administrated

Primary Outcome Measures	Measure Description	Time Frame
Number of patients alive	Number of patients alive is evaluated 12 months after the surgery	12 months
Number of patients who achieved the complete chemotherapy treatment sequences	The number of patients who achieved the complete chemotherapy treatment sequences is evaluated 12 months after the surgery	12 months

Secondary Outcome Measures	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	through end of treatment, an average of 12 months
Number of post-operative complications	Evaluation of post-operative complications is assessed using Dindo Clavien classification	1 month after surgery
Number of patients alive and without recurrence	Number of patients alive is evaluated 36 months after the surgery	36 months
Number of accomplished R0 resection surgery	Number of accomplished R0 resection surgery is evaluated by pathologists	Surgery day
Evaluation of quality of life	Evaluation of quality of life is done using EORTC QLQ C30	4 weeks after the end of chemotherapy treatment
Evaluation of quality of life	Evaluation of quality of life is done using EORTC QLQ-PAN26	4 weeks after the end of chemotherapy treatment

Contacts and Locations

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

Study Contact

Name: Lilian SCHWARZ, MD

Phone Number: +3323288

Email: lilian.schwarz@chu-rouen.fr

Study Contact Backup

Name: Julien BLOT

Phone Number:

Email: julien.blot@chu-rouen.fr

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:

Histology-proven, adenocarcinoma of the pancreas.
Resectable adenocarcinoma (according to the NCCN classification 2014): absence of distant organ or distal lymph node metastases, absence of evidence of superior mesenteric vein (SMV) and portal vein distortion, tumour thrombus, or venous encasement, the existence of clear fat planes around the celiac axis, hepatic artery and superior mesenteric artery (SMA). Resectability is evaluated on arterial-phase and portal-phase IV contrast-enhanced multislice CT-scan of the pancreas (slice thickness: 2.5 mm), as evaluated in a multidisciplinary staff meeting including at least one radiologist and one expert surgeon.
No prior chemotherapy.
Age 18 years or over.
Ability to understand and willingness to consent to formal requirements for study participation
Provision of written informed consent prior to any study-specific screening procedures.

PDAC defined as "borderline", locally advanced, non-resectable or metastatic.
Prior cancer therapy for PDAC
Surgical or anaesthesiological contra-indications: non-controlled congestive heart failure - non-treated angina - recent myocardial infarction (in the previous year) - non-controlled arterial hypertension (SBP >160 mm or DBP > 100 mm, despite optimal drug treatment), long QT, major non-controlled infection, severe liver failure.
Any medical, psychological or social situation that (in the investigator's opinion) could limit (i) the patient's compliance with the protocol or (ii) the ability to obtain or interpret data.
Pregnant or breastfeeding women and women of child-bearing age not using effective means of contraception.
History or current evidence on physical examination of central nervous system disease or peripheral neuropathy ≥ grade 1, according to according to Common Terminology Criteria for Adverse Events (CTCAE) v.4.0.
Known hypersensitivity reaction to any of the components of study treatments.
Pregnancy (the absence of which must be confirmed in a ß-hCG test) or breast-feeding.
Any significant disease which, in the investigator's opinion, would exclude the patient from the study.
Patients having been included in a clinical trial within the previous 4 weeks or participating in another trial.

Collaborators and Investigators

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

UNICANCER
Federation Francophone de Cancerologie Digestive
Federation of Research in Surgery (FRENCH)
GERCOR - Multidisciplinary Oncology Cooperative Group

Investigators

PRINCIPAL_INVESTIGATOR: Lilian SCHWARZ, MD, University Hospital, Rouen

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

Schwarz L, Vernerey D, Bachet JB, Tuech JJ, Portales F, Michel P, Cunha AS. Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study). BMC Cancer. 2018 Jul 24;18(1):762. doi: 10.1186/s12885-018-4663-4.

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Clinical Trial Record