Neoadjuvant Modified FOLFIRINOX in Borderline Resectable Pancreatic Cancer

NCT02749136 | Completed Phase 2

• 1 other identifier: AsanONCHBP-2015-001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the feasibility and efficacy outcomes of neoadjuvant modified FOLFIRINOX and postoperative gemcitabine in patients with borderline resectable pancreatic cancer.

Conditions

Pancreatic Adenocarcinoma

Keywords

Pancreatic adenocarcinoma; Borderline resectable; Neoadjuvant chemotherapy; FOLFIRINOX

Outcome Measures

Primary Outcomes (1)

• 1-year progression-free survival (PFS) rate

  PFS rate at 1 year

  1 year

Secondary Outcomes (6)

• Progression-free survival (PFS)

  3 years

• Overall survival (OS)

  3 years

• Macroscopic complete resection rate

  5 months

• Response rate

  4 months

• Toxicity profile

  1 year

Study Arms (1)

Perioperative chemotherapy

EXPERIMENTAL

* Preoperative mFOLFIRINOX, every 2 weeks, 8 cycles * Postoperative gemcitabine, every 4 weeks, 3-6 cycles

Drug: Preoperative modified FOLFIRINOX and postoperative gemcitabine

Interventions

Preoperative modified FOLFIRINOX and postoperative gemcitabine DRUG

* Preoperative mFOLFIRINOX, every 2 weeks, 8 cycles * Oxaliplatin IV 85 mg/m2 Day (D) 1 * Irinotecan IV 180 mg/m2 D1 * 5-FU continuous IV infusion 2,400 mg/m2 over 46 hours D1-2 * Leucovorin IV 400 mg/m2 D1 * Postoperative gemcitabine, every 4 weeks, 3-6 cycles - Gemcitabine 1,000 mg/ m2 D1, 8, and 15

Perioperative chemotherapy

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 19 years and older
• Cytologically or histologically confirmed adenocarcinoma of the pancreas
• Met the NCCN criteria for borderline resectable disease (assessed at Aug 23rd, 2015)
• No previous chemotherapy or radiotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status 0 \~ 1
• Adequate bone marrow function as defined by platelets ≥ 100 x 109/L and neutrophils ≥ 1.5 x 109/L
• Adequate renal function, with serum creatinine \< 1.5 x upper limit of normal (ULN)
• Adequate hepatic function with serum total bilirubin \< 2 mg/dL, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 2.5 x ULN
• No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other non life-threatening cancer (i.e., prostate or thyroid cancer) except where treated with curative intent \> 5 years previously without evidence of relapse
• Written informed consent to the study

You may not qualify if:

• No potentially resectable disease or no metastatic disease
• Locally advanced unresectable disease according to the NCCN criteria
• Histologically confirmed adenosquamous carcinoma
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance
• Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy
• Obstruction of gastrointestinal tract
• Active gastrointestinal bleeding
• Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol
• Female subjects who are pregnant or lactating, or males and females of reproductive potential not willing or not able to employ a highly effective method of birth control/contraception to prevent pregnancy from 2 weeks before receiving study drug until 3 months after receiving the last dose of study drug. A highly effective method of contraception is defined as having a low failure rate (\< 1% per year) when used consistently and correctly.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center, University of Ulsan College of Medicine

Seoul, 05505, South Korea

Location

Related Publications (11)

• Katz MH, Marsh R, Herman JM, Shi Q, Collison E, Venook AP, Kindler HL, Alberts SR, Philip P, Lowy AM, Pisters PW, Posner MC, Berlin JD, Ahmad SA. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol. 2013 Aug;20(8):2787-95. doi: 10.1245/s10434-013-2886-9. Epub 2013 Feb 23.

  PMID: 23435609 BACKGROUND

• O'Reilly EM, Perelshteyn A, Jarnagin WR, Schattner M, Gerdes H, Capanu M, Tang LH, LaValle J, Winston C, DeMatteo RP, D'Angelica M, Kurtz RC, Abou-Alfa GK, Klimstra DS, Lowery MA, Brennan MF, Coit DG, Reidy DL, Kingham TP, Allen PJ. A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma. Ann Surg. 2014 Jul;260(1):142-8. doi: 10.1097/SLA.0000000000000251.

  PMID: 24901360 BACKGROUND

• Heinemann V, Haas M, Boeck S. Neoadjuvant treatment of borderline resectable and non-resectable pancreatic cancer. Ann Oncol. 2013 Oct;24(10):2484-2492. doi: 10.1093/annonc/mdt239. Epub 2013 Jul 12.

  PMID: 23852311 BACKGROUND

• Lee JL, Kim SC, Kim JH, Lee SS, Kim TW, Park DH, Seo DW, Lee SK, Kim MH, Kim JH, Park JH, Shin SH, Han DJ. Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. Surgery. 2012 Nov;152(5):851-62. doi: 10.1016/j.surg.2012.03.010. Epub 2012 Jun 6.

  PMID: 22682078 BACKGROUND

• Heestand GM, Murphy JD, Lowy AM. Approach to patients with pancreatic cancer without detectable metastases. J Clin Oncol. 2015 Jun 1;33(16):1770-8. doi: 10.1200/JCO.2014.59.7930. Epub 2015 Apr 27.

  PMID: 25918279 BACKGROUND

• Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007 Jan 17;297(3):267-77. doi: 10.1001/jama.297.3.267.

  PMID: 17227978 BACKGROUND

• Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Olah A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Buchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010 Sep 8;304(10):1073-81. doi: 10.1001/jama.2010.1275.

  PMID: 20823433 BACKGROUND

• 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.

  PMID: 21561347 BACKGROUND

• Christians KK, Tsai S, Mahmoud A, Ritch P, Thomas JP, Wiebe L, Kelly T, Erickson B, Wang H, Evans DB, George B. Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Oncologist. 2014 Mar;19(3):266-74. doi: 10.1634/theoncologist.2013-0273. Epub 2014 Feb 25.

  PMID: 24569947 BACKGROUND

• Lim DH, Yoon H, Kim KP, Ryoo BY, Lee SS, Park DH, Song TJ, Hwang DW, Lee JH, Song KB, Kim SC, Hong SM, Hyung J, Yoo C. Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection. Cancer Res Treat. 2023 Oct;55(4):1313-1320. doi: 10.4143/crt.2023.452. Epub 2023 May 4.

  PMID: 37139665 DERIVED

• Yoo C, Lee SS, Song KB, Jeong JH, Hyung J, Park DH, Song TJ, Seo DW, Lee SK, Kim MH, Lee SS, Kim JH, Jin HS, Park JH, Hwang DW, Lee JH, Lee W, Chang HM, Kim KP, Ryoo BY, Kim SC. Neoadjuvant modified FOLFIRINOX followed by postoperative gemcitabine in borderline resectable pancreatic adenocarcinoma: a Phase 2 study for clinical and biomarker analysis. Br J Cancer. 2020 Aug;123(3):362-368. doi: 10.1038/s41416-020-0867-x. Epub 2020 May 20.

  PMID: 32433600 DERIVED

Study Officials

• Baek-Yeol Ryoo, MD, PhD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 20, 2016
• First Posted: April 22, 2016
• Study Start: May 1, 2016
• Primary Completion: September 1, 2019
• Study Completion: November 1, 2019
• Last Updated: November 25, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)