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

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ClinicalTrials.gov Identifier: NCT02676349
Recruitment Status : Recruiting
First Posted : February 8, 2016
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
Institut de Cancérologie de Lorraine

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
Pancreatic Carcinoma 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : October 13, 2016
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2026

Resource links provided by the National Library of Medicine


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)




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 [ Time Frame: up to 7.5 months ]

Secondary Outcome Measures :
  1. Evaluate the toxicities associated with chemotherapy and chemoradiotherapy [ Time Frame: up to 7 years ]
  2. Evaluate the proportion of resected patients [ Time Frame: up to 7.5 months ]
  3. Evaluate the response rate to chemotherapy and chemoradiotherapy [ Time Frame: up to 7.5 months ]
  4. Evaluate the histological complete response rate in resected patients. [ Time Frame: up to 7.5 months ]
  5. Evaluate the perioperative mortality rate [ Time Frame: up to 8.5 months ]
  6. Evaluate the perioperative morbidity rate [ Time Frame: up to 8.5 months ]
  7. Evaluate the overall survival [ Time Frame: up to 7 years ]
  8. Evaluate the quality of life [ Time Frame: up to 7.5 months ]
  9. Evaluate the loco-regional relapse-free survival [ Time Frame: 7 years ]
  10. Evaluate the metastatic Progression Free Survival [ Time Frame: 7 years ]
  11. Evaluate the progression-free survival [ Time Frame: 7 years ]


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02676349


Contacts
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Contact: Jen Louis MERLIN, Md PharmaD 03 83 59 83 07 jl.merlin@nancy.unicancer.fr
Contact: Laurinda FERNANDES 03 83 59 84 87 l.fernandes@nancy.unicancer.fr

Locations
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France
Institut Bergonié Recruiting
Bordeaux, France
Contact: BECHADE Dominique, MD         
Polyclinique Bordeaux Nord Recruiting
Bordeaux, France
Contact: LECAILLE Cédric, MD         
CHU Morvan Not yet recruiting
Brest, France
Contact: METGES Jean-Philippe, MD         
Hôpital Beaujon Recruiting
Clichy, France, 92110
Contact: HAMMEL Pascal, PR         
Chu Colmar Recruiting
Colmar, France
Contact: Gilles Breysacher, MD         
Hôpital Henri Mondor (APHP) Recruiting
Creteil, France
Contact: BAUMGAERTNER Isabelle, MD         
CH Bicêtre (APHP) Not yet recruiting
Le Kremlin-Bicêtre, France
Contact: THIROT-BIDAULT Anne, MD         
Centre Oscar Lambret Recruiting
Lille, France
Contact: Xavier Mirabel, MD         
Chru Lille Recruiting
Lille, France
Contact: PIESSEN Guillaume, MD         
Infirmerie Protestante de Lyon Recruiting
Lyon, France
Contact: TAVAN David, MD         
Hopital européen Marseille Recruiting
Marseille, France
Contact: RINALDI Yves, MD         
Hôpital La Timone Recruiting
Marseille, France
Contact: DAHAN Laëtitia, MD         
Institut Paoli CALMETTES Recruiting
Marseille, France
Contact: DELPERO Jean-Robert, MD         
Institut du Cancer de Montpellier Recruiting
Montpellier, France
Contact: PORTALES Fabienne, MD         
Chu Nantes Recruiting
Nantes, France
Contact: Nicolas REGENET, MD         
Hôpital Cochin (APHP) Recruiting
Paris, France
Contact: CORIAT Romain, MD         
Institut Mutualiste Montsouris Recruiting
Paris, France
Contact: LOUVET Christophe, MD         
Pitié Salpêtrière (APHP) Recruiting
Paris, France
Contact: BACHET Jean-Baptiste, MD         
Hôpital Haut-Lévêque Recruiting
Pessac, France
Contact: VENDRELY Véronique, MD         
CHU Reims Recruiting
Reims, France
Contact: BOUCHE Olivier, MD         
Centre Eugène Marquis Recruiting
Rennes, France
Contact: SULPICE Laurent, MD         
Chu Rouen Recruiting
Rouen, France
Contact: SCHWARZ Lillian         
CHP Saint Grégoire Recruiting
Saint Grégoire, France
Contact: MIGLIANO Laurent, MD         
Institut de Cancérologie de l'Ouest Recruiting
Saint-Herblain, France
Contact: THIBAUDEAU Emilie, MD         
Chru Tours Recruiting
Tours, France
Contact: LECOMTE Thierry, MD         
Chru Nancy Recruiting
Vandoeuvre-les-nancy, France
Contact: AYAV Ahmet, MD         
Institut de Cancérologie de Lorraine Recruiting
Vandoeuvre-les-nancy, France
Contact: CONROY Thierry, MD         
Sponsors and Collaborators
Institut de Cancérologie de Lorraine
Investigators
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Principal Investigator: Thierry CONROY, Pr Institut de Cancérologie de Lorraine
Study Chair: Jean-Baptiste BACHET, Dr Groupe Hospitalier Pitié Salpêtrière
Study Chair: Pascal HAMMEL, Pr Hôpital Beaujon Assistance Publique - Hôpitaux de Paris (AP-HP)

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Responsible Party: Institut de Cancérologie de Lorraine
ClinicalTrials.gov Identifier: NCT02676349     History of Changes
Other Study ID Numbers: 2014-005681-29
First Posted: February 8, 2016    Key Record Dates
Last Update Posted: April 3, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Institut de Cancérologie de Lorraine:
mFolfirinox
Chemoradiotherapy
Neoadjuvant treatment
Borderline
Additional relevant MeSH terms:
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Carcinoma
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases