Pancreatic CancerPhase 2FolfirinoxNCT03167112
A Study of Administering FOLFIRINOX Before Surgery For Potentially Curable Pancreatic Cancer
A Phase 2 study testing Oxaliplatin, Irinotecan and Leucovorin in people with Pancreatic Cancer, run by Petr Kavan at 1 site in Canada.
Trial summary
Pancreatic cancer is a serious condition and is one of the leading cause of cancer related health problem. It is estimated that in 2016, 5,200 Canadians will be diagnosed with pancreatic cancer, and approximately 20% (1 in 5) of patients will have localized cancer (cancer that is limited to pancreas and there is no… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Oxaliplatin, Irinotecan and Leucovorin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 3 Jul 2017to May 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must satisfy the following criteria to be enrolled in the study:
- ≥ 18 years of age at the time of signing the informed consent form.
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures conducted.
- Histologically or cytologically confirmed adenocarcinoma of the pancreas.
- Performance status or Comorbidity condition not currently appropriate (but potentially reversible) for a major abdominal operation.
- Acceptable hematology parameters:
Show all 27Show fewer
- Absolute neutrophil count (ANC) ≥ 1500 cell/mm3
- Platelet count ≥ 100,000/mm3 without transfusion support.
- Hemoglobin (Hgb) ≥ 9 g/dL
- Acceptable blood chemistry levels:
- Hepatic transaminases (ALT and AST) less than 2.5× the upper limits of normal (ULN)
- Total bilirubin level less than 1.5 × the upper limits of normal (ULN) or in patient with Biliary stenting less than 2 mg/dL
- Serum creatinine level less than 1.5 × the upper limits of normal (ULN) or creatinine clearance (Ccr) ≥ 40 mL/min.
- Alkaline phosphatase ≤ 2.5 x ULN
- Serum albumin > 3 g/dL
- Absence of poorly controlled comorbid conditions:
- Congestive heart failure (CHF)
- Chronic obstructive pulmonary disease (COPD)
- Uncontrolled diabetes mellitus (DM)
- Neurologic disorders (not acutely related to pancreatic cancer) or limit function
- Radio-graphically suspicious but not diagnostic for extra-pancreatic disease,
- Superior mesenteric vein and portal vein confluence that can be reconstructed even if short segment venous occlusion is present (i.e. a suitable portal vein above, and a suitable Superior mesenteric vein below the area of occlusion);
- Tumor abutment of the Superior mesenteric artery of ≤180⁰,
- Short segment encasement of the hepatic artery amenable to resection and reconstruction (this is usually at the origin of the gastroduodenal artery and reconstruction may or may not require interposition grafting with a short segment of reversed saphenous vein).
- Cancer antigen 19-9 level (in absence of jaundice) ≥ 100u/ml suggestive of disseminated disease.
- Preoperative treatment is recommended as an alternative for patients with potentially curable pancreatic cancer who meet all of the following criteria:
- no clinical evidence for metastatic disease, a performance status and comorbidity condition appropriate for a major abdominal operation, no radiographic interface between primary tumor and mesenteric vasculature on imaging, an acceptable Cancer antigen 19-9 level.
Who cannot join
- The presence of any of the following will exclude a subject from enrollment:
- Pancreatic tumors of endocrine or mixed origin.
- Prior anticancer therapy for pancreatic carcinoma.
- Presence of or history of metastatic pancreatic adenocarcinoma.
- Any other malignancy within 5 years prior to enrollment, with the exception of adequately treated in-situ carcinoma of the prostate (Gleason score ≤ 7), cervix, uteri, or non-melanomatous skin cancer (all treatment of which should have been completed 6 months prior to enrollment).
- Active bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.
Show all 21Show fewer
- Known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelo-suppressive medications that would, in the opinion of the Investigator, increase the risk of serious neutropenic complications.
- History of allergy or hypersensitivity to study regimen or any of their excipients.
- Peripheral sensory neuropathy Grade > 1.
- Clinically significant ascites.
- Plastic biliary stent. (Metal biliary stent is allowed.)
- Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the subject's safety or the integrity of the study data. These include, but are not limited to:
- History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa)
- History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, or multiple allergies
- History of the following within 6 months prior to treatment 1 Day 1: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or electrocardiogram (ECG) abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder
- Enrollment in any other clinical protocol or investigational study with an interventional agent or assessments that may interfere with study procedures.
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Any condition that confounds the ability to interpret data from the study.
- Unwillingness or inability to comply with study procedures.
- Pregnant or breast feeding.
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Jewish General Hospital
Montreal, Quebec, H3T 1E2
Petr Dr Kavan, MD, 5143408222, petr.kavan@mcgill.ca
About this study
Official title: A Study of Preoperative FOLFIRINOX For Potentially Curable Pancreatic Cancer
Pancreatic cancer is a serious condition and is one of the leading cause of cancer related health problem. It is estimated that in 2016, 5,200 Canadians will be diagnosed with pancreatic cancer, and approximately 20% (1 in 5) of patients will have localized cancer (cancer that is limited to pancreas and there is no evidence of cancer in other parts of the body). Localized cancer is earlier stage of disease and surgery to remove the cancer is standard of care in this condition. However, recent scientific and clinical studies show that using the chemotherapy medication before surgery can improve the overall survival in patents with localized pancreatic cancer. One of these chemotherapy regimen is combination of fluorouracil, oxaliplatin, irinotecan, leucovorin (FOLFIRINOX) that we are going to evaluate its effect in this study.
Because of promising result of this combination in more advanced stage of pancreatic cancer, this study is going to examine its efficiency in earlier stage of pancreatic cancer (localized form). Total number of participant in this study will be 20 patients with localized form of pancreatic cancer without any evidence of cancer in other parts of the body.
Read more
Laboratory tests show that it works by slowing down the growth of cancer or may cause cancer cells to die. It is hoped that by shrinking the tumor size, the surgeon will be able to remove the cancer and improve the overall survival.
Procedures start with 2 weeks of comprehensive evaluation. Approximately 20 eligible subjects, based on this study criteria, will receive 6 treatment of this regimen every 2 weeks. Once 6 treatments have been completed, comprehensive re-evaluation procedures will be repeated, and subjects without disease progression or unacceptable toxicity will continue on their treatment based on treating team decision (surgical intervention, radiation therapy or continue FOLFIRINOX or different regimen). Patients then will follow with CT scan, blood test and physical examination every 3 months.
Read the detailed description
Approximately 20% of patients present with potentially curable pancreatic cancers-resectable or borderline resectable tumors- for which surgical resection is an appropriate consideration. However, even after multimodality therapy that includes surgical resection, 5-year OS rates only reach 25% to 30% at best.
Surgical resection represents the standard of care for patients with early-stage pancreatic cancer. However, while surgical morbidity and mortality have improved over the past few decades, overall survival for pancreatic cancer has remained low. Given the increasing survival rates associated with modern chemotherapy regimens, the risks of surgery, the likelihood of R0 resection, the likelihood of subclinical metastatic disease, and the likelihood of receiving postoperative therapy (50% of patients receive post-operative chemotherapy) are our logic to evaluate preoperative chemotherapy as an alternative treatment strategy for these patients.
The main advantage of neoadjuvant chemotherapy in treating pancreatic cancer is that it significantly increases the likelihood of receiving both surgery and chemotherapy. (Winner et al., Seminars in Oncology, 2015). It is well accepted that the best results are achieved when both modalities are used. Recently, the use of FOLFIRINOX has emerged as an alternative in pancreatic cancer. A randomized trial of FOLFIRINOX versus gemcitabine in metastatic pancreatic cancer showed improved median survival from 6.8 to 11.1 months.
According to ACCORD-11 trial,FOLFIRINOX in advanced metastatic disease have demonstrated improved response rates compared with gemcitabine and other historical treatments while maintaining or improving quality of life with the median overall survival was 11.1 months FOLFIRINOX group as compared with 6.8 months in the gemcitabine group. Median progression-free survival was 6.4 months in the study regimen group and 3.3 months in the gemcitabine group, and at 6 months, 31% of the patients FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group.
The role of preoperative therapy for patients with potentially curable pancreatic cancer is still unclear. The ongoing study (adjuvant gemcitabine versus neoadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer) is a prospective randomized clinical trial that is anticipated to clarify the role of preoperative chemotherapy. However, this ongoing clinical trial does not use contemporary chemotherapy regimens with proven efficacy in higher stage settings such as FOLFIRINOX. There are only few studies evaluate this regimen in this setting.The encouraging results reported from ACCORD-11 and consequent clinical investigations prompted our group to evaluate our experience with FOLFIRINOX regimen in a selected population composed of patients with potentially curable pancreatic cancer (resectable and borderline resectable).
In this clinical trial, our primary objective is to evaluate and estimate Time to Progression (TTP). However, our secondary objectives are to determine Overall Response Rate (ORR), R0 and R1 Resection Rate, assessment of safety and toxicity associated with study regimen, and finally, to investigate Overall survival (OS).
Pre-treatment procedures start with 2 weeks of comprehensive staging evaluation. Approximately 20 eligible subjects, based on inclusion/exclusion criteria will receive study regimen for 6 treatment every 2 weeks. Once 6 treatments have been completed, comprehensive re-staging procedures will be repeated, and subjects without disease progression or unacceptable toxicity will continue on their treatment contingent upon treating team decision (surgical intervention, radiation therapy or continue chemotherapy with FOLFIRINOX or different regimen). Patients then follow with CT scan, cancer antigen 19-9 and physical examination every 3 months.
Subjects will be considered active study participants from enrollment up to survival follow-up period until documented disease progression, withdrawal of consent, lost to follow-up, or death (by any cause), whichever is earliest.
- Conditions
- Pancreatic Cancer
- Being tested
- Oxaliplatin, Irinotecan, Leucovorin, Fluorouracil
- Keywords
- Potentially Curable, Preoperative, FOLFIRINOX
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxaliplatinDrug
Also called Study regimen
Patients receive Oxaliplatin 85 mg/m2 over 2 hours.
IrinotecanDrug
Also called Study regimen
Oxaliplatin is followed by Irinotecan (CPT-11) 180 mg/m2 over 90 min.
LeucovorinDrug
Also called Study regimen
Oxaliplatin and Irinotecan is followed by Leucovorin (LV) 400 mg/m2 over 2 hours day1
FluorouracilDrug
Also called Study regimen
Oxaliplatin and Irinotecan and Leucovorin is followed by Fluorouracil (5-FU) 400 mg/m2 bolus day1 and 2,400 mg/m2 46h continuous infusion.
| Study group | Role | What they receive |
|---|---|---|
| FOLFIRINOX | Experimental | Oxaliplatin, Irinotecan, Leucovorin, Fluorouracil Receives: Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin; Drug: Fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Progression (TTP).
Time to Progression (TTP) is defined as the time from the first cycle of chemotherapy until objective tumor progression.
Measured: Through study completion, an average of 1 year.
Secondary outcomes (4)
Overall Response Rate
Overall response rate will be summarized based on RECIST V1.1
Measured: Through study completion, an average of 1 year
Residual (R) tumor status
The R classification is based on International Union Against Cancer (UICC).
Measured: Through study completion, an average of 1 year.
Incidence of Treatment related Adverse Events [Safety and Tolerability]
Safety and toxicity variable is the incidence of treatment related adverse effect, serious adverse effect, laboratory abnormalities and other safety parameters.
Measured: Through study completion, an average of 1 year.
Overall survival (OS)
Overall survival indicates the interval between the first cycle of chemotherapy and the occurrence of death from any cause.
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2017
- Study start3 Jul 2017
- Primary completionMar 2018 (estimated)
- Study completionMay 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Petr Kavan
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Petr Kavan, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Petr Kavan, MD, PhD, Principal investigator, McGill University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03167112
- Sponsor's protocol ID
- CODIM-MBM-17-040
- Acronym
- Folfirinox
- Status last verified
- Aug 2017
- First submitted
- 14 May 2017
- Last updated
- 29 Aug 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913-21. doi: 10.1158/0008-5472.CAN-14-0155.
PubMed 24840647Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics, 2006. CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30. doi: 10.3322/canjclin.56.2.106.
PubMed 16514137Katz MH, Wang H, Fleming JB, Sun CC, Hwang RF, Wolff RA, Varadhachary G, Abbruzzese JL, Crane CH, Krishnan S, Vauthey JN, Abdalla EK, Lee JE, Pisters PW, Evans DB. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol. 2009 Apr;16(4):836-47. doi: 10.1245/s10434-008-0295-2. Epub 2009 Feb 5.
PubMed 19194760Winter JM, Brennan MF, Tang LH, D'Angelica MI, Dematteo RP, Fong Y, Klimstra DS, Jarnagin WR, Allen PJ. Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. Ann Surg Oncol. 2012 Jan;19(1):169-75. doi: 10.1245/s10434-011-1900-3. Epub 2011 Jul 15.
PubMed 21761104Katz 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.
PubMed 23435609Tempero MA, Arnoletti JP, Behrman SW, Ben-Josef E, Benson AB 3rd, Casper ES, Cohen SJ, Czito B, Ellenhorn JD, Hawkins WG, Herman J, Hoffman JP, Ko A, Komanduri S, Koong A, Ma WW, Malafa MP, Merchant NB, Mulvihill SJ, Muscarella P 2nd, Nakakura EK, Obando J, Pitman MB, Sasson AR, Tally A, Thayer SP, Whiting S, Wolff RA, Wolpin BM, Freedman-Cass DA, Shead DA; National Comprehensive Cancer Networks. Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw. 2012 Jun 1;10(6):703-13. doi: 10.6004/jnccn.2012.0073.
PubMed 22679115Oettle 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.
PubMed 17227978Smeenk HG, van Eijck CH, Hop WC, Erdmann J, Tran KC, Debois M, van Cutsem E, van Dekken H, Klinkenbijl JH, Jeekel J. Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891. Ann Surg. 2007 Nov;246(5):734-40. doi: 10.1097/SLA.0b013e318156eef3.
PubMed 17968163Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985 Aug;120(8):899-903. doi: 10.1001/archsurg.1985.01390320023003.
PubMed 4015380Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, Arnaud JP, Gonzalez DG, de Wit LT, Hennipman A, Wils J. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg. 1999 Dec;230(6):776-82; discussion 782-4. doi: 10.1097/00000658-199912000-00006.
PubMed 10615932O'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.
PubMed 24901360Merkow RP, Bilimoria KY, Tomlinson JS, Paruch JL, Fleming JB, Talamonti MS, Ko CY, Bentrem DJ. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014 Aug;260(2):372-7. doi: 10.1097/SLA.0000000000000378.
PubMed 24374509Wu W, He J, Cameron JL, Makary M, Soares K, Ahuja N, Rezaee N, Herman J, Zheng L, Laheru D, Choti MA, Hruban RH, Pawlik TM, Wolfgang CL, Weiss MJ. The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy for adenocarcinoma. Ann Surg Oncol. 2014 Sep;21(9):2873-81. doi: 10.1245/s10434-014-3722-6. Epub 2014 Apr 26.
PubMed 24770680Yamada S, Fujii T, Sugimoto H, Nomoto S, Takeda S, Kodera Y, Nakao A. Aggressive surgery for borderline resectable pancreatic cancer: evaluation of National Comprehensive Cancer Network guidelines. Pancreas. 2013 Aug;42(6):1004-10. doi: 10.1097/MPA.0b013e31827b2d7c.
PubMed 23532000Bao P, Potter D, Eisenberg DP, Lenzner D, Zeh HJ, Lee Iii KK, Hughes SJ, Sanders MK, Young JL, Moser AJ. Validation of a prediction rule to maximize curative (R0) resection of early-stage pancreatic adenocarcinoma. HPB (Oxford). 2009 Nov;11(7):606-11. doi: 10.1111/j.1477-2574.2009.00110.x.
PubMed 20495714
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Preoperative FOLFIRINOX For Potentially Curable Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT03167112
- Acronym / sponsor ID
- Folfirinox / CODIM-MBM-17-040
- Conditions
- Pancreatic Cancer
- Keywords
- Potentially Curable, Preoperative, FOLFIRINOX
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Petr KavanUniversity, hospital or other
- Study start
- 3 Jul 2017 (actual)
- Primary completion
- Mar 2018 (estimated)
- Study completion
- May 2018 (estimated)
- First posted
- 25 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pancreatic cancer is a serious condition and is one of the leading cause of cancer related health problem. It is estimated that in 2016, 5,200 Canadians will be diagnosed with pancreatic cancer, and approximately 20% (1 in 5) of patients will have localized cancer (cancer that is limited to pancreas and there is no evidence of cancer in other parts of the body). Localized cancer is earlier stage of disease and surgery to remove the cancer is standard of care in this condition. However, recent scientific and clinical studies show that using the chemotherapy medication before surgery can improve the overall survival in patents with localized pancreatic cancer. One of these chemotherapy regimen is combination of fluorouracil, oxaliplatin, irinotecan, leucovorin (FOLFIRINOX) that we are going to evaluate its effect in this study.
Because of promising result of this combination in more advanced stage of pancreatic cancer, this study is going to examine its efficiency in earlier stage of pancreatic cancer (localized form). Total number of participant in this study will be 20 patients with localized form of pancreatic cancer without any evidence of cancer in other parts of the body.
Laboratory tests show that it works by slowing down the growth of cancer or may cause cancer cells to die. It is hoped that by shrinking the tumor size, the surgeon will be able to remove the cancer and improve the overall survival.
Procedures start with 2 weeks of comprehensive evaluation. Approximately 20 eligible subjects, based on this study criteria, will receive 6 treatment of this regimen every 2 weeks. Once 6 treatments have been completed, comprehensive re-evaluation procedures will be repeated, and subjects without disease progression or unacceptable toxicity will continue on their treatment based on treating team decision (surgical intervention, radiation therapy or continue FOLFIRINOX or different regimen). Patients then will follow with CT scan, blood test and physical examination every 3 months.
Detailed description
Approximately 20% of patients present with potentially curable pancreatic cancers-resectable or borderline resectable tumors- for which surgical resection is an appropriate consideration. However, even after multimodality therapy that includes surgical resection, 5-year OS rates only reach 25% to 30% at best.
Surgical resection represents the standard of care for patients with early-stage pancreatic cancer. However, while surgical morbidity and mortality have improved over the past few decades, overall survival for pancreatic cancer has remained low. Given the increasing survival rates associated with modern chemotherapy regimens, the risks of surgery, the likelihood of R0 resection, the likelihood of subclinical metastatic disease, and the likelihood of receiving postoperative therapy (50% of patients receive post-operative chemotherapy) are our logic to evaluate preoperative chemotherapy as an alternative treatment strategy for these patients.
The main advantage of neoadjuvant chemotherapy in treating pancreatic cancer is that it significantly increases the likelihood of receiving both surgery and chemotherapy. (Winner et al., Seminars in Oncology, 2015). It is well accepted that the best results are achieved when both modalities are used. Recently, the use of FOLFIRINOX has emerged as an alternative in pancreatic cancer. A randomized trial of FOLFIRINOX versus gemcitabine in metastatic pancreatic cancer showed improved median survival from 6.8 to 11.1 months.
According to ACCORD-11 trial,FOLFIRINOX in advanced metastatic disease have demonstrated improved response rates compared with gemcitabine and other historical treatments while maintaining or improving quality of life with the median overall survival was 11.1 months FOLFIRINOX group as compared with 6.8 months in the gemcitabine group. Median progression-free survival was 6.4 months in the study regimen group and 3.3 months in the gemcitabine group, and at 6 months, 31% of the patients FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group.
The role of preoperative therapy for patients with potentially curable pancreatic cancer is still unclear. The ongoing study (adjuvant gemcitabine versus neoadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer) is a prospective randomized clinical trial that is anticipated to clarify the role of preoperative chemotherapy. However, this ongoing clinical trial does not use contemporary chemotherapy regimens with proven efficacy in higher stage settings such as FOLFIRINOX. There are only few studies evaluate this regimen in this setting.The encouraging results reported from ACCORD-11 and consequent clinical investigations prompted our group to evaluate our experience with FOLFIRINOX regimen in a selected population composed of patients with potentially curable pancreatic cancer (resectable and borderline resectable).
In this clinical trial, our primary objective is to evaluate and estimate Time to Progression (TTP). However, our secondary objectives are to determine Overall Response Rate (ORR), R0 and R1 Resection Rate, assessment of safety and toxicity associated with study regimen, and finally, to investigate Overall survival (OS).
Pre-treatment procedures start with 2 weeks of comprehensive staging evaluation. Approximately 20 eligible subjects, based on inclusion/exclusion criteria will receive study regimen for 6 treatment every 2 weeks. Once 6 treatments have been completed, comprehensive re-staging procedures will be repeated, and subjects without disease progression or unacceptable toxicity will continue on their treatment contingent upon treating team decision (surgical intervention, radiation therapy or continue chemotherapy with FOLFIRINOX or different regimen). Patients then follow with CT scan, cancer antigen 19-9 and physical examination every 3 months.
Subjects will be considered active study participants from enrollment up to survival follow-up period until documented disease progression, withdrawal of consent, lost to follow-up, or death (by any cause), whichever is earliest.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FOLFIRINOX | Experimental | Drug: Oxaliplatin, Drug: Irinotecan, Drug: Leucovorin, Drug: FluorouracilOxaliplatin, Irinotecan, Leucovorin, Fluorouracil |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Subjects must satisfy the following criteria to be enrolled in the study:
- no clinical evidence for metastatic disease, a performance status and comorbidity condition appropriate for a major abdominal operation, no radiographic interface between primary tumor and mesenteric vasculature on imaging, an acceptable Cancer antigen 19-9 level.
Key exclusion criteria (21 listed)
- The presence of any of the following will exclude a subject from enrollment:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OxaliplatinAlso: Study regimenPatients receive Oxaliplatin 85 mg/m2 over 2 hours. | Drug | FOLFIRINOX |
| IrinotecanAlso: Study regimenOxaliplatin is followed by Irinotecan (CPT-11) 180 mg/m2 over 90 min. | Drug | FOLFIRINOX |
| LeucovorinAlso: Study regimenOxaliplatin and Irinotecan is followed by Leucovorin (LV) 400 mg/m2 over 2 hours day1 | Drug | FOLFIRINOX |
| FluorouracilAlso: Study regimenOxaliplatin and Irinotecan and Leucovorin is followed by Fluorouracil (5-FU) 400 mg/m2 bolus day1 and 2,400 mg/m2 46h continuous infusion. | Drug | FOLFIRINOX |
Primary outcome
Time to Progression (TTP).
Time frame: Through study completion, an average of 1 year.
Time to Progression (TTP) is defined as the time from the first cycle of chemotherapy until objective tumor progression.
4 secondary outcomes
Overall Response Rate
Time frame: Through study completion, an average of 1 year
Residual (R) tumor status
Time frame: Through study completion, an average of 1 year.
Incidence of Treatment related Adverse Events [Safety and Tolerability]
Time frame: Through study completion, an average of 1 year.
Overall survival (OS)
Time frame: Through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2017.
- Results publication: PubMed 24840647Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913-21. doi: 10.1158/0008-5472.CAN-14-0155.
- Results publication: PubMed 16514137Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics, 2006. CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30. doi: 10.3322/canjclin.56.2.106.
- Results publication: PubMed 19194760Katz MH, Wang H, Fleming JB, Sun CC, Hwang RF, Wolff RA, Varadhachary G, Abbruzzese JL, Crane CH, Krishnan S, Vauthey JN, Abdalla EK, Lee JE, Pisters PW, Evans DB. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol. 2009 Apr;16(4):836-47. doi: 10.1245/s10434-008-0295-2. Epub 2009 Feb 5.
- Results publication: PubMed 21761104Winter JM, Brennan MF, Tang LH, D'Angelica MI, Dematteo RP, Fong Y, Klimstra DS, Jarnagin WR, Allen PJ. Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. Ann Surg Oncol. 2012 Jan;19(1):169-75. doi: 10.1245/s10434-011-1900-3. Epub 2011 Jul 15.
- Results publication: PubMed 23435609Katz 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.
- Results publication: PubMed 22679115Tempero MA, Arnoletti JP, Behrman SW, Ben-Josef E, Benson AB 3rd, Casper ES, Cohen SJ, Czito B, Ellenhorn JD, Hawkins WG, Herman J, Hoffman JP, Ko A, Komanduri S, Koong A, Ma WW, Malafa MP, Merchant NB, Mulvihill SJ, Muscarella P 2nd, Nakakura EK, Obando J, Pitman MB, Sasson AR, Tally A, Thayer SP, Whiting S, Wolff RA, Wolpin BM, Freedman-Cass DA, Shead DA; National Comprehensive Cancer Networks. Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw. 2012 Jun 1;10(6):703-13. doi: 10.6004/jnccn.2012.0073.
- Results publication: PubMed 17227978Oettle 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.
- Results publication: PubMed 17968163Smeenk HG, van Eijck CH, Hop WC, Erdmann J, Tran KC, Debois M, van Cutsem E, van Dekken H, Klinkenbijl JH, Jeekel J. Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891. Ann Surg. 2007 Nov;246(5):734-40. doi: 10.1097/SLA.0b013e318156eef3.
- Results publication: PubMed 4015380Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985 Aug;120(8):899-903. doi: 10.1001/archsurg.1985.01390320023003.
- Results publication: PubMed 10615932Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, Arnaud JP, Gonzalez DG, de Wit LT, Hennipman A, Wils J. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg. 1999 Dec;230(6):776-82; discussion 782-4. doi: 10.1097/00000658-199912000-00006.
- Results publication: PubMed 24901360O'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.
- Results publication: PubMed 24374509Merkow RP, Bilimoria KY, Tomlinson JS, Paruch JL, Fleming JB, Talamonti MS, Ko CY, Bentrem DJ. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014 Aug;260(2):372-7. doi: 10.1097/SLA.0000000000000378.
- Individual participant dataSharing planned: Undecided
Related trials for Pancreatic Cancer
Not yet recruitingPhase 1/2
A Study of Perioperative Navlimetostat Combined With Modified FOLFIRINOX in Patients With MTAP-Deleted Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma (PDAC)
Active, not recruitingObservational study
Long-term Observational Study to Evaluate the DFS and OS of Adjuvant FOLFIRINOX Regimen in Pancreatic Cancer Patients
Adjuvant Chemotherapy
Active, not recruitingPhase 1/2
A Study of GKL-006 Injection in Patients With Advanced Pancreatic Cancer
Advanced Pancreatic Cancer, Ductal Adenocarcinoma of Pancreas
RecruitingPhase 2
A Study of Navlimetostat (BMS-986504) Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion (MountainTAP-5)
Solid Tumors
Active, not recruitingPhase 2
A Phase 2 Study of T-DXd in Patients With Selected HER2 Expressing Tumors
Part 1: Bladder, Biliary Tract, Cervical, Endometrial, Ovarian, Pancreatic Cancer, Rare Tumors, Any Tumor Type Excluding Breast, Gastric, Colorectal Cancer, Part 2: HER2 Expressing/Amplified Solid Tumors Excluding Breast, Gastric, Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Petr Kavan, MD, PhD principal investigator
McGill University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oxaliplatin, Irinotecan and Leucovorin in people with Pancreatic Cancer, run by Petr Kavan at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Petr Kavan, MD, PhD (+1-514340-8222 ext. 23460, petr.kavan@mcgill.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Progression (TTP). (time frame: Through study completion, an average of 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03167112, which also lists 28 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2017.