Pancreatic Cancer and Synchronous Liver Metastases Resection Following Neoadjuvant FOLFIRINOX

Pancreas Cancer Clinical Trial

— PDAC-LIV  

Official title:

Pancreatic Cancer and Synchronous Liver Metastases Resection Following Neoadjuvant FOLFIRINOX: a Prospective, Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06349278
• Other study ID #: 2024-7276
• Status: Recruiting
• Phase: N/A
• Start date: January 16, 2024
• Est. completion date: January 16, 2029

Study information

• Verified date: April 2024
• Source: Laval University
• Contact: Alexandre Brind'Amour, MD, MSc
• Phone: 418-691-5370
• Email: alexandre.brindamour.1[@]ulaval.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, pilot study from a single center. Patients will be evaluated and operated on by one of five surgeons with a subspeciality in hepato-biliary and pancreatic surgery. After thorough, standard of care assessment for both pancreatic primary and liver metastases resectability with blood tumor markers (CEA, CA 19-9 and CA-125), triphasic CT-scan and liver magnetic resonance imaging (MRI), patients with resectable pancreatic ductal adenocarcinoma primary and three or less resectable liver metastases will be prospectively included in the study. PET-scan may be added to the investigation depending on CT-scan or MRI results to prove metastatic disease or rule out extrahepatic metastases. Patients will receive a total of 12 cycles of perioperative FOLFIRINOX (FFX), with first reassessment with triphasic CT-scan to monitor tumor response after the first six cycles. Every patient will receive at least 6 cycles of FFX before surgery. The remaining six cycles will be received either preoperatively or postoperatively, depending on patient tolerance and tumor response at reassessment. Patients with liver metastases only visible on MRI will also have liver MRI at reassessment, which is also standard of care. Patients with evidence of tumor response on both imaging using RECIST V.1.1 criteria (stable disease or partial response), and blood tumor markers (≥ 80% decrease and/or normalization of all tumor markers) will then undergo pancreatic resection, either distal pancreatectomy or pancreatoduodenectomy depending on tumor side, with liver metastases excision. Each case will be followed with blood tumor markers and CT-scan every three months for two years, and every four months afterwards or until recurrence, which is standard of care for patients with metastatic PDAC. For patients without evidence of tumor response on imaging, or < 80% decrease of all tumor markers, the standard palliative systemic treatment will be continued.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: January 16, 2029
• Est. primary completion date: January 16, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of pancreatic ductal adenocarcinoma (PDAC).
• Resectable primary tumor based on triphasic CT-scan.
• = 3 liver metastases.
• Liver resections can be performed by local excision or non-anatomical, partial hepatectomy. Patients with complete radiologic response after neoadjuvant FOLFIRINOX (FFX), therefore not requiring liver resection, will be included.
• No evidence of extrahepatic metastases.
• Patient fit for pancreatic resection (ECOG 0 or 1).
• Stable or partial response on imaging after neoadjuvant FFX.
• No new metastasis after neoadjuvant FFX
• Blood tumor markers = 80% decreased or within normal values after neoadjuvant FFX.

Exclusion Criteria:

• Impossibility to obtain tissue diagnosis preoperatively confirming PDAC.
• Locally advanced disease on triphasic CT-scan.
• > 3 liver metastases.
• Major hepatectomy required for liver metastases (right hepatectomy, left hepatectomy, central hepatectomy, extended right or left hepatectomy).
• Suspicion or confirmation of extrahepatic metastases.
• Patient unfit for pancreatic resection (ECOG 2 or more).
• Contraindication to receive FFX.

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Pancreas Adenocarcinoma
• Pancreas Cancer
• Pancreas Metastases
• Pancreatic Neoplasms

Intervention

Procedure:
• Pancreatic resection and non-anatomic liver resections.
Pancreatic resection and non-anatomic liver resections.

Locations

Country	Name	City	State
Canada	CHU de Québec	Quebec City	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Laval University

Country where clinical trial is conducted

Canada, 

References & Publications (15)

Assenat E, de la Fouchardiere C, Portales F, Ychou M, Debourdeau A, Desseigne F, Iltache S, Fiess C, Mollevi C, Mazard T. Sequential first-line treatment with nab-paclitaxel/gemcitabine and FOLFIRINOX in metastatic pancreatic adenocarcinoma: GABRINOX phase Ib-II controlled clinical trial. ESMO Open. 2021 Dec;6(6):100318. doi: 10.1016/j.esmoop.2021.100318. Epub 2021 Nov 24. — View Citation

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Chun JW, Lee SH, Kim JS, Park N, Huh G, Cho IR, Paik WH, Ryu JK, Kim YT. Comparison between FOLFIRINOX and gemcitabine plus nab-paclitaxel including sequential treatment for metastatic pancreatic cancer: a propensity score matching approach. BMC Cancer. 2021 May 11;21(1):537. doi: 10.1186/s12885-021-08277-7. — View Citation

Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923. — View Citation

Crippa S, Cirocchi R, Weiss MJ, Partelli S, Reni M, Wolfgang CL, Hackert T, Falconi M. A systematic review of surgical resection of liver-only synchronous metastases from pancreatic cancer in the era of multiagent chemotherapy. Updates Surg. 2020 Mar;72(1):39-45. doi: 10.1007/s13304-020-00710-z. Epub 2020 Jan 29. — View Citation

De La Cruz MS, Young AP, Ruffin MT. Diagnosis and management of pancreatic cancer. Am Fam Physician. 2014 Apr 15;89(8):626-32. — View Citation

Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goere D, Seufferlein T, Haustermans K, Van Laethem JL, Conroy T, Arnold D; ESMO Guidelines Committee. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep;26 Suppl 5:v56-68. doi: 10.1093/annonc/mdv295. No abstract available. Erratum In: Ann Oncol. 2017 Jul 1;28(suppl_4):iv167-iv168. — View Citation

Hashimoto D, Satoi S, Fujii T, Sho M, He J, Hackert T, Del Chiaro M, Jang JY, Gulla A, Yoon YS, Shan YS, Lou W, Valente R, Furuse J, Oba A, Nagai M, Terai T, Tanaka H, Sakai A, Yamamoto T, Yamaki S, Matsumoto I, Murakami Y, Takaori K, Takeyama Y. Is surgical resection justified for pancreatic ductal adenocarcinoma with distant abdominal organ metastasis? A position paper by experts in pancreatic surgery at the Joint Meeting of the International Association of Pancreatology (IAP) & the Japan Pancreas Society (JPS) 2022 in Kyoto. Pancreatology. 2023 Sep;23(6):682-688. doi: 10.1016/j.pan.2023.07.005. Epub 2023 Jul 20. — View Citation

Hishinuma S, Ogata Y, Tomikawa M, Ozawa I, Hirabayashi K, Igarashi S. Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings. J Gastrointest Surg. 2006 Apr;10(4):511-8. doi: 10.1016/j.gassur.2005.09.016. — View Citation

Lee JC, Woo SM, Shin DW, Kim J, Yang SY, Kim MJ, Kim JW, Kim JW, Lee WJ, Cha HS, Park P, Kim J, Hwang JH. Comparison of FOLFIRINOX and Gemcitabine Plus Nab-paclitaxel for Treatment of Metastatic Pancreatic Cancer: Using Korean Pancreatic Cancer (K-PaC) Registry. Am J Clin Oncol. 2020 Sep;43(9):654-659. doi: 10.1097/COC.0000000000000730. — View Citation

Otsuka T, Shirakawa T, Shimokawa M, Koga F, Kawaguchi Y, Ueda Y, Nakazawa J, Komori A, Otsu S, Arima S, Fukahori M, Okabe Y, Makiyama A, Taguchi H, Honda T, Shibuki T, Nio K, Ide Y, Mizuta T, Mitsugi K, Ureshino N. A multicenter propensity score analysis of FOLFIRINOX vs gemcitabine plus nab-paclitaxel administered to patients with metastatic pancreatic cancer: results from the NAPOLEON study. Int J Clin Oncol. 2021 May;26(5):941-950. doi: 10.1007/s10147-021-01859-2. Epub 2021 Jan 23. Erratum In: Int J Clin Oncol. 2021 Mar 3;: — View Citation

Rawla P, Sunkara T, Gaduputi V. Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol. 2019 Feb;10(1):10-27. doi: 10.14740/wjon1166. Epub 2019 Feb 26. — View Citation

Sakaguchi T, Valente R, Tanaka K, Satoi S, Del Chiaro M. Surgical treatment of metastatic pancreatic ductal adenocarcinoma: A review of current literature. Pancreatology. 2019 Jul;19(5):672-680. doi: 10.1016/j.pan.2019.05.466. Epub 2019 Jun 7. — View Citation

Sohal DPS, Kennedy EB, Khorana A, Copur MS, Crane CH, Garrido-Laguna I, Krishnamurthi S, Moravek C, O'Reilly EM, Philip PA, Ramanathan RK, Ruggiero JT, Shah MA, Urba S, Uronis HE, Lau MW, Laheru D. Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2018 Aug 20;36(24):2545-2556. doi: 10.1200/JCO.2018.78.9636. Epub 2018 May 23. — View Citation

Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Morbidity and mortality	Post-operative complications	90 days
Secondary	Overall survival	Overall survival	3 years after surgery