Neoadjuvant Modified FOLFIRINOX in Borderline Resectable Pancreatic Cancer

NCT ID: NCT02749136

Last Updated: 2019-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-31

Study Completion Date

2019-11-30

Brief Summary

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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.

Detailed Description

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Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. The 5-year survival rate in overall patients is less than 6% due to late clinical manifestation and the systemic nature of the disease at presentation. Even in patients with resectable disease, estimated 5-year survival rates after resection are between 15% and 20%. Traditionally, resection alone is regarded as inadequate for cure. Therefore, systemic and/or combined chemotherapy and radiotherapy have been used as preoperative or postoperative therapy.

Neoadjuvant treatment offers several theoretical advantages over an initial resection. Early delivery of systemic therapy for all patients which might lead to the higher rates of negative margin resection rate, and enhanced patient selection for surgery. Although neoadjuvant treatment has been established as a standard of care for resectable or locally advanced disease of breast, gastric, and rectal cancers, the role of neoadjuvant treatment in patients with pancreatic cancer is not clear at present.

There is no global consensus on the management of patients with borderline resectable pancreatic cancer. If initially resected, postoperative adjuvant chemotherapy or chemoradiotherapy is standard. However, there is no standard regimen for neoadjuvant chemotherapy for pancreatic cancer. Recent pivotal phase 2/3 trial has demonstrated that FOLFIRINOX improved the response rates and survival outcomes of patients with metastatic pancreatic cancer compared to gemcitabine.

Because of higher response rates (about 30%) with FOLFIRINOX, this regimen is now widely investigated in the neoadjuvant setting. Therefore, investigators hypothesize that neoadjuvant FOLFIRINOX may enhance the outcomes of patients with borderline resectable pancreatic cancer. This study will assess the feasibility and efficacy outcomes of neoadjuvant modified FOLFIRINOX and postoperative gemcitabine in patients with borderline resectable pancreatic cancer.

Conditions

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Pancreatic Adenocarcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Perioperative chemotherapy

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

Group Type EXPERIMENTAL

Preoperative modified FOLFIRINOX and postoperative gemcitabine

Intervention Type 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

Interventions

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Preoperative modified FOLFIRINOX and postoperative gemcitabine

* 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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Asan Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Baek-Yeol Ryoo

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Baek-Yeol Ryoo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center

Locations

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Asan Medical Center, University of Ulsan College of Medicine

Seoul, , South Korea

Site Status

Countries

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South Korea

References

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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.

Reference Type BACKGROUND
PMID: 24569947 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37139665 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23435609 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24901360 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23852311 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22682078 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25918279 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17227978 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20823433 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21561347 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32433600 (View on PubMed)

Other Identifiers

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AsanONCHBP-2015-001

Identifier Type: -

Identifier Source: org_study_id

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