Neoadjuvant Modified FOLFIRINOX in Borderline Resectable Pancreatic Cancer

Pancreatic Adenocarcinoma Clinical Trial

Official title:

Phase 2 Study of Neoadjuvant Modified FOLFIRINOX in Patients With Borderline Resectable Pancreas Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02749136
• Other study ID #: AsanONCHBP-2015-001
• Status: Completed
• Phase: Phase 2
• Start date: May 2016
• Est. completion date: November 2019

Study information

• Verified date: November 2019
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: November 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Adenocarcinoma

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center, University of Ulsan College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (9)

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. — View Citation

Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé 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

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. Review. — View Citation

Heinemann V, Haas M, Boeck S. Neoadjuvant treatment of borderline resectable and non-resectable pancreatic cancer. Ann Oncol. 2013 Oct;24(10):2484-92. doi: 10.1093/annonc/mdt239. Epub 2013 Jul 12. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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, Oláh A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Büchler 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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-year progression-free survival (PFS) rate	PFS rate at 1 year	1 year
Secondary	Progression-free survival (PFS)	Median PFS	3 years
Secondary	Overall survival (OS)	Median OS	3 years
Secondary	Macroscopic complete resection rate	The rate of no gross residual disease after surgery	5 months
Secondary	Response rate	Response rate defined by Response Evaluation Criteria in Solid Tumor version 1.1	4 months
Secondary	Toxicity profile	Adverse events graded by National Cancer Institute Common Terminology Criteria version 4.03	1 year
Secondary	Biomarker analysis	Blood-based biomarker analysis for the correlation with response rate, progression-free survival and overall survival	3 years