Ignite Creation Date:
2024-05-06 @ 10:34 AM
Last Modification Date:
2024-10-26 @ 12:32 PM
Study NCT ID:
NCT03291899
Status:
TERMINATED
Last Update Posted:
2024-01-17
First Post:
2017-09-21
Brief Title:
Trial of Infusional FOLFIRINOX in First Line Treatment of Advanced Biliary Tract Cancers
Sponsor:
King Faisal Specialist Hospital Research Center
Organization:
King Faisal Specialist Hospital Research Center
Study Overview
Official Title:
Phase II Trial of Infusional 5 FLUOROURACIL LEUCOVORIN OXALIPLATIN AND IRINOTECAN FOLFIRINOX in First Line Treatment of Advanced Biliary Tract Cancers
Status:
TERMINATED
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
poor accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FBI-TRAC
Brief Summary:
This study is to evaluate the response rate and toxicity profile of infusional 5 fluorouracil leucovorin oxaliplatin and irinotecan FOLFIRINOX in first-line treatment of advanced biliary tract cancers and also to assess progression free survival and overall survival of FOLFIRINOX in first line treatment of advanced biliary tract cancers
Detailed Description:
Biliary tract carcinomas BTCs are invasive adenocarcinomas that arise from the epithelial cells of the biliary tree which comprises intrahepatic and extrahepatic bile ducts and the gallbladder Even though BTCs are considered as rare tumors they represent about 30 of the total primary liver cancers with an incidence rate close to that of hepatocellular carcinoma Approximately 1200 new cases in the United Kingdom and 9000 in the United States are diagnosed annually The Saudi Cancer Registry reported 911 case of gall bladder cancer 318 intrahepatic cholangiocarcinoma and 574 extrahepatic cholangiocarcinoma between 1994 and 2009 Unfortunately only a minority of patients diagnosed with these aggressive tumors present at an early resectable stage and disease recurrence rates are high despite curative-intent surgery
The prognosis of patients with advanced biliary tract cancers is poor and median survival for those undergoing supportive care alone is short Systemic chemotherapy is increasingly being applied in cases of advanced biliary tract cancers A benefit for chemotherapy over best supportive care alone was suggested in a trial that randomly assigned 90 patients with advanced pancreatic or biliary cancer 37 with bile duct cancer to fluorouracil FU-based systemic chemotherapy or best supportive care alone with median survival of 6 months for chemotherapy versus 25 months for best supportive care
Different drugs has demonstrated activity in BTCs including fluoropyrimidines gemcitabine cisplatin and oxaliplatin A pooled analysis from Eckel et al that evaluated 104 trials with 2810 patients has established gemcitabine combined with platinum compounds as the provisional standard of chemotherapy in advanced biliary tract cancer
In a randomized phase two study of 51 patients Kornek et al established the efficacy of mitomycin in combination with gemcitabine or capecitabine in previously untreated patients with advanced biliary tract cancers Mitomycin and capecitabine was associated with superior complete response rate 31 vs 20 median progression free survival 53 months vs 42 months and overall survival 925 months and 67 months The EORTC 40955 trial randomized patients with BTCs to high dose 5FU vs combination of 5-FU Leucovorin and cisplatin The results showed that cisplatin and fluorouracil was more active than high-dose fluorouracil in terms of overall response rates 19 and 71 respectively and overall survival 8 months and 5 months respectively but progression free surviva was similar in both treatment arms 33 months
The randomized controlled phase three ABC-02 study which enrolled 410 patients with locally advanced or metastatic cholangiocarcinoma gallbladder cancer or ampullary cancer demonstrated that the combination of gemcitabine and cisplatin improved overall and progression free survival by 30 over gemcitabine alone Median overall survival was 117 months vs 81 months HR 064 95 confidence interval 052-080 p001 and progression free survival was 8 months HR 051 95 confidence interval 051-077 p001 both in favor of the combination arm Although the rate of neutropenia was higher in the group receiving gemcitabine and cisplatin there was no significant difference in the rate of neutropenia-associated infections between the 2 arms Okusaka et al also reported similar findings in a phase two randomized study of 84 patients with advanced biliary tract cancers Based on these results the combination of gemcitabine and cisplatin is considered to be the standard of care for first-line chemotherapy for patients with advanced or metastatic biliary tract cancers
Triple-drug chemotherapy regimens also have been shown to be effective in patients with advanced biliary tract cancers albeit in a very small number of patients The phase three trial that evaluated fluorouracil leucovorin and etoposide versus fluorouracil cisplatin and epirubicin didnt show one regimen to be significantly superior with respect to overall survival 12 months vs 9 months respectively in patients with advanced biliary tract cancers although the trial was underpowered to detect such a difference
In a phase two trial the combination panitumumab a monoclonal anti-epidermal growth factor receptor antibody with gemcitabine and irinotecan showed encouraging efficacy with good tolerability in patients with advanced cholangiocarcinoma with 5-month progression free survival rate of 69The median progression free survival and overall survival were 97 months and 129 months respectively
Results from the randomized phase three PRODIGE trial evaluating the combination of 5-Fluorouracil Leucovorin oxaliplatin and Irinotecan FOLFIRINOX versus gemcitabine alone in patients with metastatic pancreatic cancer and good performance status showed dramatic improvements in both median PFS 64 vs 33 months P 001 and median OS 111 months vs 68 months P 001 Because of these strong results the National comprehensive cancer network NCCN and many other societies added FOLFIRINOX as a preferred category 1 recommendation for first line treatment of good performance status patients with metastatic pancreatic cancer in 2011
There are however some concerns about the toxicity of FOLFIRINOX regimen In the PRODIGE trial some of the grade 3 and 4 toxicity rates that were significantly greater in the FOLFIRINOX group than in the gemcitabine group were 457 for neutropenia 127 for diarrhea and 91 for thrombocytopenia and 9 for sensory neuropathy
Despite the high levels of toxicity no toxic deaths have been reported Furthermore the PRODIGE trial determined that despite this toxicity fewer patients in the FOLFIRINOX group than in the gemcitabine group experienced a degradation in their quality of life at 6 months 31 vs 66p 001 A more detailed analysis of the quality of life of patients in this trial has been published and shows that FOLFIRINOX maintained and even improved quality of life more than gemcitabine did
Based on the above data the investigators designed this phase two study of the efficacy and toxicity of FOFIRINOX regimen in first line treatment for patients with advanced biliary tract cancers If the investigators achieved encouraging results this regimen should then be compared with the standard combination of gemcitabine and cisplatin in future phase three trials
The prognosis of patients with advanced biliary tract cancers is poor and median survival for those undergoing supportive care alone is short Systemic chemotherapy is increasingly being applied in cases of advanced biliary tract cancers A benefit for chemotherapy over best supportive care alone was suggested in a trial that randomly assigned 90 patients with advanced pancreatic or biliary cancer 37 with bile duct cancer to fluorouracil FU-based systemic chemotherapy or best supportive care alone with median survival of 6 months for chemotherapy versus 25 months for best supportive care
Different drugs has demonstrated activity in BTCs including fluoropyrimidines gemcitabine cisplatin and oxaliplatin A pooled analysis from Eckel et al that evaluated 104 trials with 2810 patients has established gemcitabine combined with platinum compounds as the provisional standard of chemotherapy in advanced biliary tract cancer
In a randomized phase two study of 51 patients Kornek et al established the efficacy of mitomycin in combination with gemcitabine or capecitabine in previously untreated patients with advanced biliary tract cancers Mitomycin and capecitabine was associated with superior complete response rate 31 vs 20 median progression free survival 53 months vs 42 months and overall survival 925 months and 67 months The EORTC 40955 trial randomized patients with BTCs to high dose 5FU vs combination of 5-FU Leucovorin and cisplatin The results showed that cisplatin and fluorouracil was more active than high-dose fluorouracil in terms of overall response rates 19 and 71 respectively and overall survival 8 months and 5 months respectively but progression free surviva was similar in both treatment arms 33 months
The randomized controlled phase three ABC-02 study which enrolled 410 patients with locally advanced or metastatic cholangiocarcinoma gallbladder cancer or ampullary cancer demonstrated that the combination of gemcitabine and cisplatin improved overall and progression free survival by 30 over gemcitabine alone Median overall survival was 117 months vs 81 months HR 064 95 confidence interval 052-080 p001 and progression free survival was 8 months HR 051 95 confidence interval 051-077 p001 both in favor of the combination arm Although the rate of neutropenia was higher in the group receiving gemcitabine and cisplatin there was no significant difference in the rate of neutropenia-associated infections between the 2 arms Okusaka et al also reported similar findings in a phase two randomized study of 84 patients with advanced biliary tract cancers Based on these results the combination of gemcitabine and cisplatin is considered to be the standard of care for first-line chemotherapy for patients with advanced or metastatic biliary tract cancers
Triple-drug chemotherapy regimens also have been shown to be effective in patients with advanced biliary tract cancers albeit in a very small number of patients The phase three trial that evaluated fluorouracil leucovorin and etoposide versus fluorouracil cisplatin and epirubicin didnt show one regimen to be significantly superior with respect to overall survival 12 months vs 9 months respectively in patients with advanced biliary tract cancers although the trial was underpowered to detect such a difference
In a phase two trial the combination panitumumab a monoclonal anti-epidermal growth factor receptor antibody with gemcitabine and irinotecan showed encouraging efficacy with good tolerability in patients with advanced cholangiocarcinoma with 5-month progression free survival rate of 69The median progression free survival and overall survival were 97 months and 129 months respectively
Results from the randomized phase three PRODIGE trial evaluating the combination of 5-Fluorouracil Leucovorin oxaliplatin and Irinotecan FOLFIRINOX versus gemcitabine alone in patients with metastatic pancreatic cancer and good performance status showed dramatic improvements in both median PFS 64 vs 33 months P 001 and median OS 111 months vs 68 months P 001 Because of these strong results the National comprehensive cancer network NCCN and many other societies added FOLFIRINOX as a preferred category 1 recommendation for first line treatment of good performance status patients with metastatic pancreatic cancer in 2011
There are however some concerns about the toxicity of FOLFIRINOX regimen In the PRODIGE trial some of the grade 3 and 4 toxicity rates that were significantly greater in the FOLFIRINOX group than in the gemcitabine group were 457 for neutropenia 127 for diarrhea and 91 for thrombocytopenia and 9 for sensory neuropathy
Despite the high levels of toxicity no toxic deaths have been reported Furthermore the PRODIGE trial determined that despite this toxicity fewer patients in the FOLFIRINOX group than in the gemcitabine group experienced a degradation in their quality of life at 6 months 31 vs 66p 001 A more detailed analysis of the quality of life of patients in this trial has been published and shows that FOLFIRINOX maintained and even improved quality of life more than gemcitabine did
Based on the above data the investigators designed this phase two study of the efficacy and toxicity of FOFIRINOX regimen in first line treatment for patients with advanced biliary tract cancers If the investigators achieved encouraging results this regimen should then be compared with the standard combination of gemcitabine and cisplatin in future phase three trials
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None