Neoadjuvant vs Upfront Surgery for Resectable Pancreatic Cancer and Periampullary Cancer

NCT ID: NCT07081360

Last Updated: 2025-08-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 262 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-20
• Study Completion Date: 2028-08-20

Brief Summary

Adjuvant chemotherapy after surgery significantly improved the survival of pancreatic cancer (PC) patients, but there is a problem that only about 50% of patients start adjuvant chemotherapy after pancreatectomy. Neoadjuvant chemotherapy might control potential metastatic lesions which are not being detected in early disease status and improve the R0 resection rate. In addition, it prevents futile surgery by selecting patients with rapid progression of disease. Furthermore, compared to chemotherapy administered after surgery, more patients can complete the planned chemotherapy schedule in neoadjuvant setting.

There are still few studies worldwide that prospectively explored the efficacy of neoadjuvant chemotherapy in resectable PC and periampullary cancer and the administration of neoadjuvant therapy in resectable PC depends on individual clinical judgment. Therefore, systematic and prospective clinical trials are essential to standardize treatment protocol in resectable PC and periampullary Cancer.

This randomized controlled trial compares neoadjuvant chemotherapy followed by surgery versus upfront surgery for patients with clearly resectable pancreatic head cancer and periampullary cancer. The study aims to determine if neoadjuvant chemotherapy improves overall survival compared to immediate surgery followed by adjuvant chemotherapy.

Detailed Description

Pancreatic cancer is the seventh highest cause of death from cancer worldwide, with only 20% of patients presenting with resectable disease. Despite potentially curative resections, 5-year survival remains at 20%. This study evaluates whether neoadjuvant chemotherapy can improve outcomes by eliminating occult metastatic disease and improving resection margins.

Patients with clearly resectable pancreatic head cancer or periampullary cancer will be randomized 1:1 to either neoadjuvant chemotherapy followed by open or laparoscopic pancreaticoduodenectomy (Arm A) or upfront laparoscopic pancreaticoduodenectomy followed by adjuvant chemotherapy (Arm B). The primary endpoint is overall survival, with secondary endpoints including R0 resection rate , disease-free survival and perioperative outcomes.

Conditions

Pancreas Cancer; Periampullary Cancer; Periampullary Carcinoma Resectable; Pancreatic Cancer Resectable; Ampullary Cancer; Pancreas Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant chemotherapy group (mFOLFIRINOX)

Neoadjuvant chemotherapy(mFOLFIRINOX) followed by pancreaticoduodenectomy

Group Type: EXPERIMENTAL

Neoadjuvant chemotherapy

Intervention Type: DRUG

Neoadjuvant chemotherapy (mFOLFIRINOX) followed by pancreaticoduodenectomy

Upfront Surgery Group

Pancreaticoduodenectomy followed by adjuvant chemotherapy

Group Type: ACTIVE_COMPARATOR

Upfront Surgery Group

Intervention Type: PROCEDURE

Pancreaticoduodenectomy followed by adjuvant chemotherapy

Interventions

Neoadjuvant chemotherapy

Neoadjuvant chemotherapy (mFOLFIRINOX) followed by pancreaticoduodenectomy

Intervention Type: DRUG

Upfront Surgery Group

Pancreaticoduodenectomy followed by adjuvant chemotherapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed pancreatic head cancer or periampullary carcinoma(endoscopic ultrasound (EUS)-guided biopsy).
• Clearly resectable disease as defined by National Comprehensive Cancer Network (NCCN) criteria on cross-sectional imaging:

No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery .

Less than 180 degree interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence No evidence of metastatic disease.

• Eastern Cooperative Oncology Group (ECOG)=0-1 & American Society of Anesthesiologists (ASA) score <4.
• Written informed consent.
• Medical history without previous pancreatic resection or pancreatic cancer.
• Adequate organ function (liver, kidney, bone marrow) (serum creatinine ≤2.0 mg/dL,reference range 0.5-1.20 mg/dL; serum albumin ≥2.5 g/dL, reference range 3.5-5.3; aspartate aminotransferase (AST) ≤95 U/L, reference range 0-38; Alanine aminotransferase (ALT) ≤102 U/L, reference range 0-41; prothrombin time ≤1.8, reference range 0-1.20; partial thromboplastin time ≤1.8, reference range 0.82-1.25; leukocyte count greater than 3.5×109/L, reference range 4.2-9.0; platelet count greater than 100×109/L, reference range 130-400; hemoglobin ≥9 g/dL, reference range 12-16).

Exclusion Criteria

• Borderline resectable or locally advanced pancreatic or periampullary cancer.
• Tumor at the body or tail of the pancreas.
• Distant metastases.
• Prior chemotherapy , surgery or radiotherapy for pancreatic cancer.
• Severe comorbidities precluding surgery or chemotherapy.
• Pregnancy or lactation.
• Other neoplastic diseases (malignant)diagnosed in the past 5 years.
• Major surgery or traumatic event in the past 28 days.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Minia University

OTHER

Sponsor Role: lead

Responsible Party

Saleh Khairy Saleh MD

Lecturer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Saleh K Saleh, MD

Role: PRINCIPAL_INVESTIGATOR

Minia University

Locations

Liver and GIT hospital , Minia University

Minya, Minya Governorate, Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Saleh K Saleh, MD

Role: CONTACT

salehkhairy@mu.edu.eg

+201201765401 ext. +2

Rabeh K Saleh, MD

Role: CONTACT

Rabeh.Saleh@mu.edu.eg

+201220065443 ext. +2

Facility Contacts

Saleh K Saleh

Role: primary

salehkhairy@mu.edu.eg

01201765401 ext. +2

References

Evans DB. The Complexity of Neoadjuvant Therapy for Operable Pancreatic Cancer: Lessons Learned From SWOG S1505. Ann Surg. 2020 Sep 1;272(3):487. doi: 10.1097/SLA.0000000000004131. No abstract available.

Reference Type: BACKGROUND

PMID: 32657915 (View on PubMed)

Murphy JE, Wo JY, Ryan DP, Jiang W, Yeap BY, Drapek LC, Blaszkowsky LS, Kwak EL, Allen JN, Clark JW, Faris JE, Zhu AX, Goyal L, Lillemoe KD, DeLaney TF, Fernandez-Del Castillo C, Ferrone CR, Hong TS. Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial. JAMA Oncol. 2018 Jul 1;4(7):963-969. doi: 10.1001/jamaoncol.2018.0329.

Reference Type: BACKGROUND

PMID: 29800971 (View on PubMed)

Golcher H, Brunner TB, Witzigmann H, Marti L, Bechstein WO, Bruns C, Jungnickel H, Schreiber S, Grabenbauer GG, Meyer T, Merkel S, Fietkau R, Hohenberger W. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial. Strahlenther Onkol. 2015 Jan;191(1):7-16. doi: 10.1007/s00066-014-0737-7. Epub 2014 Sep 25.

Reference Type: BACKGROUND

PMID: 25252602 (View on PubMed)

Casadei R, Di Marco M, Ricci C, Santini D, Serra C, Calculli L, D'Ambra M, Guido A, Morselli-Labate AM, Minni F. Neoadjuvant Chemoradiotherapy and Surgery Versus Surgery Alone in Resectable Pancreatic Cancer: A Single-Center Prospective, Randomized, Controlled Trial Which Failed to Achieve Accrual Targets. J Gastrointest Surg. 2015 Oct;19(10):1802-12. doi: 10.1007/s11605-015-2890-4. Epub 2015 Jul 30.

Reference Type: BACKGROUND

PMID: 26224039 (View on PubMed)

Goetze TO, Reichart A, Bankstahl US, Pauligk C, Loose M, Kraus TW, Elshafei M, Bechstein WO, Trojan J, Behrend M, Homann N, Venerito M, Bohle W, Varvenne M, Bolling C, Behringer DM, Kratz-Albers K, Siegler GM, Hozaeel W, Al-Batran SE. Adjuvant Gemcitabine Versus Neoadjuvant/Adjuvant FOLFIRINOX in Resectable Pancreatic Cancer: The Randomized Multicenter Phase II NEPAFOX Trial. Ann Surg Oncol. 2024 Jun;31(6):4073-4083. doi: 10.1245/s10434-024-15011-7. Epub 2024 Mar 8.

Reference Type: BACKGROUND

PMID: 38459418 (View on PubMed)

Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010 Apr 20;7(4):e1000267. doi: 10.1371/journal.pmed.1000267.

Reference Type: BACKGROUND

PMID: 20422030 (View on PubMed)

Artinyan A, Anaya DA, McKenzie S, Ellenhorn JD, Kim J. Neoadjuvant therapy is associated with improved survival in resectable pancreatic adenocarcinoma. Cancer. 2011 May 15;117(10):2044-9. doi: 10.1002/cncr.25763. Epub 2010 Nov 18.

Reference Type: BACKGROUND

PMID: 21523715 (View on PubMed)

Mokdad AA, Minter RM, Zhu H, Augustine MM, Porembka MR, Wang SC, Yopp AC, Mansour JC, Choti MA, Polanco PM. Neoadjuvant Therapy Followed by Resection Versus Upfront Resection for Resectable Pancreatic Cancer: A Propensity Score Matched Analysis. J Clin Oncol. 2017 Feb 10;35(5):515-522. doi: 10.1200/JCO.2016.68.5081. Epub 2016 Sep 30.

Reference Type: BACKGROUND

PMID: 27621388 (View on PubMed)

Lee YS, Lee JC, Yang SY, Kim J, Hwang JH. Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis. Sci Rep. 2019 Oct 30;9(1):15662. doi: 10.1038/s41598-019-52167-9.

Reference Type: BACKGROUND

PMID: 31666626 (View on PubMed)

Bradley A, Van Der Meer R. Upfront Surgery versus Neoadjuvant Therapy for Resectable Pancreatic Cancer: Systematic Review and Bayesian Network Meta-analysis. Sci Rep. 2019 Mar 13;9(1):4354. doi: 10.1038/s41598-019-40951-6.

Reference Type: BACKGROUND

PMID: 30867522 (View on PubMed)

Ye M, Zhang Q, Chen Y, Fu Q, Li X, Bai X, Liang T. Neoadjuvant chemotherapy for primary resectable pancreatic cancer: a systematic review and meta-analysis. HPB (Oxford). 2020 Jun;22(6):821-832. doi: 10.1016/j.hpb.2020.01.001. Epub 2020 Jan 27.

Reference Type: BACKGROUND

PMID: 32001139 (View on PubMed)

Adam MA, Nassour I, Hoehn R, Hlavin CA, Bahary N, Bartlett DL, Lee KKW, Zureikat AH, Paniccia A. Neoadjuvant Chemotherapy for Pancreatic Adenocarcinoma Lessens the Deleterious Effect of Omission of Adjuvant Chemotherapy. Ann Surg Oncol. 2021 Jul;28(7):3800-3807. doi: 10.1245/s10434-020-09446-x. Epub 2021 Jan 1.

Reference Type: BACKGROUND

PMID: 33386547 (View on PubMed)

Birrer DL, Golcher H, Casadei R, Haile SR, Fritsch R, Hussung S, Brunner TB, Fietkau R, Meyer T, Grutzmann R, Merkel S, Ricci C, Ingaldi C, Di Marco M, Guido A, Serra C, Minni F, Pestalozzi B, Petrowsky H, DeOliveira M, Bechstein WO, Bruns CJ, Oberkofler CE, Puhan M, Lesurtel M, Heinrich S, Clavien PA. Neoadjuvant Therapy for Resectable Pancreatic Cancer: A New Standard of Care. Pooled Data From 3 Randomized Controlled Trials. Ann Surg. 2021 Nov 1;274(5):713-720. doi: 10.1097/SLA.0000000000005126.

Reference Type: BACKGROUND

PMID: 34334656 (View on PubMed)

Ghanem I, Lora D, Herradon N, de Velasco G, Carretero-Gonzalez A, Jimenez-Varas MA, Vazquez de Parga P, Feliu J. Neoadjuvant chemotherapy with or without radiotherapy versus upfront surgery for resectable pancreatic adenocarcinoma: a meta-analysis of randomized clinical trials. ESMO Open. 2022 Jun;7(3):100485. doi: 10.1016/j.esmoop.2022.100485. Epub 2022 May 14.

Reference Type: BACKGROUND

PMID: 35580504 (View on PubMed)

van Dam JL, Janssen QP, Besselink MG, Homs MYV, van Santvoort HC, van Tienhoven G, de Wilde RF, Wilmink JW, van Eijck CHJ, Groot Koerkamp B; Dutch Pancreatic Cancer Group. Neoadjuvant therapy or upfront surgery for resectable and borderline resectable pancreatic cancer: A meta-analysis of randomised controlled trials. Eur J Cancer. 2022 Jan;160:140-149. doi: 10.1016/j.ejca.2021.10.023. Epub 2021 Nov 24.

Reference Type: BACKGROUND

PMID: 34838371 (View on PubMed)

Versteijne E, Suker M, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, Buijsen J, Busch OR, Creemers GM, van Dam RM, Eskens FALM, Festen S, de Groot JWB, Groot Koerkamp B, de Hingh IH, Homs MYV, van Hooft JE, Kerver ED, Luelmo SAC, Neelis KJ, Nuyttens J, Paardekooper GMRM, Patijn GA, van der Sangen MJC, de Vos-Geelen J, Wilmink JW, Zwinderman AH, Punt CJ, van Eijck CH, van Tienhoven G; Dutch Pancreatic Cancer Group. Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial. J Clin Oncol. 2020 Jun 1;38(16):1763-1773. doi: 10.1200/JCO.19.02274. Epub 2020 Feb 27.

Reference Type: BACKGROUND

PMID: 32105518 (View on PubMed)

Pingpank JF, Hoffman JP, Ross EA, Cooper HS, Meropol NJ, Freedman G, Pinover WH, LeVoyer TE, Sasson AR, Eisenberg BL. Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas. J Gastrointest Surg. 2001 Mar-Apr;5(2):121-30. doi: 10.1016/s1091-255x(01)80023-8.

Reference Type: BACKGROUND

PMID: 11331473 (View on PubMed)

van Geenen RC, van Gulik TM, Offerhaus GJ, de Wit LT, Busch OR, Obertop H, Gouma DJ. Survival after pancreaticoduodenectomy for periampullary adenocarcinoma: an update. Eur J Surg Oncol. 2001 Sep;27(6):549-57. doi: 10.1053/ejso.2001.1162.

Reference Type: BACKGROUND

PMID: 11520088 (View on PubMed)

Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Chone L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Breysacher G, Di Fiore F, Cripps C, Kavan P, Texereau P, Bouhier-Leporrier K, Khemissa-Akouz F, Legoux JL, Juzyna B, Gourgou S, O'Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet JB; Canadian Cancer Trials Group and the Unicancer-GI-PRODIGE Group. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018 Dec 20;379(25):2395-2406. doi: 10.1056/NEJMoa1809775.

Reference Type: BACKGROUND

PMID: 30575490 (View on PubMed)

Snyder RA, Parikh AA. Actual Survival in Patients with Resected Pancreatic Cancer: How Do Real-World Data Compare with Clinical Trial Evidence? Ann Surg Oncol. 2021 Dec;28(13):8014-8016. doi: 10.1245/s10434-021-10532-x. Epub 2021 Sep 12. No abstract available.

Reference Type: BACKGROUND

PMID: 34514521 (View on PubMed)

van Dam JL, Verkolf EMM, Dekker EN, Bonsing BA, Bratlie SO, Brosens LAA, Busch OR, van Driel LMJW, van Eijck CHJ, Feshtali S, Ghorbani P, de Groot DJA, de Groot JWB, Haberkorn BCM, de Hingh IH, van der Holt B, Karsten TM, van der Kolk MB, Labori KJ, Liem MSL, Loosveld OJL, Molenaar IQ, Polee MB, van Santvoort HC, de Vos-Geelen J, Wumkes ML, van Tienhoven G, Homs MYV, Besselink MG, Wilmink JW, Groot Koerkamp B; Dutch Pancreatic Cancer Group. Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): study protocol for a multicenter randomized controlled trial. BMC Cancer. 2023 Aug 7;23(1):728. doi: 10.1186/s12885-023-11141-5.

Reference Type: BACKGROUND

PMID: 37550634 (View on PubMed)

Labori KJ, Bratlie SO, Andersson B, Angelsen JH, Biorserud C, Bjornsson B, Bringeland EA, Elander N, Garresori H, Gronbech JE, Haux J, Hemmingsson O, Liljefors MG, Myklebust TA, Nymo LS, Peltola K, Pfeiffer P, Sallinen V, Sandstrom P, Sparrelid E, Stenvold H, Soreide K, Tingstedt B, Verbeke C, Ohlund D, Klint L, Dueland S, Lassen K; Nordic Pancreatic Cancer Trial-1 study group. Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2024 Mar;9(3):205-217. doi: 10.1016/S2468-1253(23)00405-3. Epub 2024 Jan 15.

Reference Type: BACKGROUND

PMID: 38237621 (View on PubMed)

Other Identifiers

1563/06/2025

Identifier Type: -

Identifier Source: org_study_id