Neoadjuvant mFolfirinox With or Without Preoperative Concomitant Chemoradiotherapy in Patients With Borderline Resectable Pancreatic Carcinoma (PANDAS-PRODIGE 44)

Institut de Cancérologie de Lorraine (Other)
Overall Status
Recruiting ID

Study Details

Study Description

Brief Summary

This is a prospective, randomized phase II trial. The aim of this study is to assess the efficacy of two therapeutics strategies. Patients with borderline-resectable pancreatic cancer (BRPC) will be randomly in two arms : neoadjuvant mFolfirinox followed with or without preoperative chemoradiotherapy with capecitabine.

Condition or Disease Intervention/Treatment Phase
  • Drug: mFolfirinox
  • Radiation: Chemoradiotherapy
  • Procedure: surgery
  • Drug: Adjuvant chemotherapy
Phase 2

Detailed Description

Surgery, especially if followed by adjuvant chemotherapy, offers the only chance of cure of pancreatic cancer. At first diagnosis, after careful assessment, only 10 to 15% of patients are considered to be candidates for surgical resection and about 7% have a potentially resectable disease. These potentially resectable tumors called "borderline resectable pancreatic cancer" (BRPC) are conceptualized as those that involve the mesenteric vasculature to a limited extent and those for which resection, while possible, would likely be compromised by positive surgical margins (R1) in the absence of neoadjuvant treatment. R0 resection is indeed considered as an independent prognostic factor for survival when the surgical procedures, histological examination and definition of microscopic invasion are standardized.

The objectives of neoadjuvant treatments of BRPC is to reduce tumor volume before surgery in order to improve the chances of radical (R0) resection and to reduce the rate of lymph node positivity and recurrences. The primary outcome in published studies is usually R0 resection rate, but these results also depend on the number of margins examined and the definition of microscopic margin involvement. Prospective studies with consistent selection criteria and standardized assessment criteria are needed.

Different neoadjuvant therapeutic strategies have been tested in pilot studies: preoperative chemoradiotherapy or neoadjuvant chemotherapy, followed or not by a preoperative (chemo)radiotherapy. Due to the lack of randomized studies, the best sequence of treatment administration has not been established.

The aim of this prospective, randomized, multicenter, trial is to evaluate the R0 resection rate with neoadjuvant Folfirinox, followed or not by radiochemotherapy for patients with borderline resectable pancreatic cancers.

Study Design

Study Type:
Anticipated Enrollment :
90 participants
Intervention Model:
Parallel Assignment
None (Open Label)
Primary Purpose:
Official Title:
Two Arm, Prospective, Multicenter Randomized Phase II Trial of Neoadjuvant Modified Folfirinox Regimen, With or Without Preoperative Concomitant Chemoradiotherapy in Patients With Borderline Resectable Pancreatic Carcinoma
Actual Study Start Date :
Oct 13, 2016
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm B

Neoadjuvant chemotherapy with mFolfirinox regimen + concomitant chemoradiotherapy + surgery + adjuvant chemotherapy

Drug: mFolfirinox
oxaliplatin folinic acid irinotecan 5FU oxaliplatin

Radiation: Chemoradiotherapy
conformational external irradiation (50.4 Gy) + capecitabine

Procedure: surgery
1 to 4 weeks after neoadjuvant treatment according to tumour response

Drug: Adjuvant chemotherapy
Gemcitabine or modified LV5FU (folinic acid+-bolus fluorouracil+ infusional fluorouracil)

Active Comparator: Arm A

Neoadjuvant chemotherapy with mFolfirinox regimen + surgery + adjuvant chemotherapy

Drug: mFolfirinox
oxaliplatin folinic acid irinotecan 5FU oxaliplatin

Procedure: surgery
1 to 4 weeks after neoadjuvant treatment according to tumour response

Drug: Adjuvant chemotherapy
Gemcitabine or modified LV5FU (folinic acid+-bolus fluorouracil+ infusional fluorouracil)

Outcome Measures

Primary Outcome Measures

  1. To assess the efficacy of two neoadjuvant therapies in patients with borderline resectable pancreatic carcinoma evaluated on histological R0 resection margin rate [up to 7.5 months]

Secondary Outcome Measures

  1. Evaluate the toxicities associated with chemotherapy and chemoradiotherapy [up to 7 years]

  2. Evaluate the proportion of resected patients [up to 7.5 months]

  3. Evaluate the response rate to chemotherapy and chemoradiotherapy [up to 7.5 months]

  4. Evaluate the histological complete response rate in resected patients. [up to 7.5 months]

  5. Evaluate the perioperative mortality rate [up to 8.5 months]

  6. Evaluate the perioperative morbidity rate [up to 8.5 months]

  7. Evaluate the overall survival [up to 7 years]

  8. Evaluate the quality of life [up to 7.5 months]

  9. Evaluate the loco-regional relapse-free survival [7 years]

  10. Evaluate the metastatic Progression Free Survival [7 years]

  11. Evaluate the progression-free survival [7 years]

Eligibility Criteria


Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Inclusion Criteria:
  • ECOG performance status 0 or 1

  • Adult patients ≥ 18 years and ≤ 75 years of age

  • Histologic or cytologic proven adenocarcinoma of the pancreas (histologic confirmation of diagnosis is preferred)

  • Confirmation by independent multidisciplinary expert review of borderline resectable status, according to NCCN-Clinical Practice Guidelines in Oncology "pancreatic adenocarcinoma", version 1.2015.

  • Adequate hematologic function, as follows:

  • absolute neutrophil count (ANC) ≥ > 2000/mm3

  • platelet count ≥ 100 000/mm3

  • haemoglobin ≥ 10 g/dL

  • Adequate renal, hepatic and bone marrow function, defined as:

  • Calculated creatinine clearance ≥ 50 mL/min according to MDRD formula

  • Serum total bilirubin ≤ 1.5 times the institutional upper limit of normal. Patients with a biliary short metal stent due to cancer obstruction may be included provided that high-quality imaging is performed before stenting and bilirubin level after stent insertion decreased to ≤ 20 mg/L (≤ 34 µmol/l), and there is no cholangitis.

  • Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner)

  • for male subject: during the treatment and for up to 6 months after the last dose of oxaliplatin or up to 3 months after the last dose of irinotcan.

  • for female subject: during the treatment and for up to 4 months after the last dose of oxaliplatin or up to 3 months after the last dose of irinotcan.

  • Ability to provide written informed consent before the start of any study specific procedures

  • Patient's legal capacity to consent to study participation and to understand and comply with the requirements of the study.

Exclusion Criteria:
  • Any previous treatment of the pancreatic cancer except biliary short metal stenting (chemotherapy, targeted tumor therapy, local ablative therapy, previous irradiation within the actual fields of planned radiotherapy)

  • Evidence of distant metastases including ascites

  • Evidence of extent of pancreatic cancer beyond that defined as "borderline resectable" : suspicious lymphadenopathy outside of the standard field of resection (i.e., aortocaval nodes, distant abdominal nodes)

  • Contraindication for pancreas resection

  • Pregnant or breast feeding females

  • Patients with known Gilbert's Syndrome or homozygosity for UGT1A1*28 polymorphism

  • Uracilemia ≥ 16ng/mL either a partial or complete deficiency in dihydropyrimidine dehydrogenase (DPD)

  • Participation in any other clinical trial or treatment with any experimental drug within 28 days before enrolment to the study or during study participation until the end of treatment visit that can be interfering with the objectives of the study

  • Previous or concurrent malignant tumor disease other than underlying tumor disease (with the exception of cervical cancer in situ, adequately treated non-melanoma skin cancers, superficial bladder tumors (Ta, Tis, and T1) or any curatively treated without chemotherapy and favourable prognosis tumors without evidence of disease for > 3 years prior to enrolment)

  • Any severe and/or uncontrolled medical conditions including but not limited to:

  • Clinically significant cardiovascular or vascular disease : angina pectoris (even controlled), previous myocardial infarction, serious uncontrolled cardiac arrhythmia, chronic heart failure, acute or chronic infectious disease requiring general treatment)

  • Acute and chronic, active infectious disorders that requires systemic treatment

  • Peripheral polyneuropathy > grade 1

  • Any previous inflammatory disease of colon or rectum

  • Any other severe concomitant disease or disorder, which could influence patient's ability to participate in the study and his/her safety during the study e.g. severe hepatic, renal, pulmonary, metabolic, or psychiatric disorders

  • Uncorrected disturbed electrolyte balance, in particular hypokalemia or hypocalcemia

  • Hypersensitivity against any of the study drugs (gemcitabine, oxaliplatin, irinotecan, 5-fluorouracil, folinic acid), or the ingredients of these drugs (e.g. fructose).

Contacts and Locations


Site City State Country Postal Code
1 Institut Bergonié Bordeaux France
2 Polyclinique Bordeaux Nord Bordeaux France
3 CHU Morvan Brest France
4 Hôpital Beaujon Clichy France 92110
5 Chu Colmar Colmar France
6 Hôpital Henri Mondor (APHP) Creteil France
7 CH Bicêtre (APHP) Le Kremlin-Bicêtre France
8 Centre Oscar Lambret Lille France
9 Chru Lille Lille France
10 Infirmerie Protestante de Lyon Lyon France
11 Hôpital Européen Marseille Marseille France
12 Hôpital La Timone Marseille France
13 Institut Paoli CALMETTES Marseille France
14 Institut du Cancer de Montpellier Montpellier France
15 Chu Nantes Nantes France
16 Hôpital Cochin (APHP) Paris France
17 Institut Mutualiste Montsouris Paris France
18 Pitié Salpêtrière (APHP) Paris France
19 Hôpital Haut-Lévêque Pessac France
20 CHU Reims Reims France
21 Centre Eugène Marquis Rennes France
22 Chu Rouen Rouen France
23 CHP Saint Grégoire Saint Grégoire France
24 Institut de Cancérologie de l'Ouest Saint-Herblain France
25 Chru Tours Tours France
26 Chru Nancy Vandoeuvre-les-nancy France
27 Institut de Cancérologie de Lorraine Vandoeuvre-les-nancy France
28 Hôpital Paul Brousse Villejuif France 94804

Sponsors and Collaborators

  • Institut de Cancérologie de Lorraine


  • Principal Investigator: Thierry CONROY, Pr, Institut de Cancérologie de Lorraine
  • Study Chair: Jean-Baptiste BACHET, Pr, Groupe Hospitalier Pitié-Salpêtrière
  • Study Chair: Pascal HAMMEL, Pr, Hôpital Paul Brousse - Hôpitaux de Paris (AP-HP)

Study Documents (Full-Text)

None provided.

More Information


None provided.
Responsible Party:
Institut de Cancérologie de Lorraine Identifier:
Other Study ID Numbers:
  • 2014-005681-29
First Posted:
Feb 8, 2016
Last Update Posted:
Mar 31, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:
Keywords provided by Institut de Cancérologie de Lorraine
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 31, 2022