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Trial record 1 of 852 for:    Pancreatic Cancer AND Progression-free survival
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Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer (FOLFIRINOX)

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ClinicalTrials.gov Identifier: NCT01523457
Recruitment Status : Completed
First Posted : February 1, 2012
Results First Posted : August 30, 2017
Last Update Posted : August 30, 2017
Sponsor:
Information provided by (Responsible Party):
Yale University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Metastatic Pancreatic Cancer
Pancreatic Cancer
Intervention Drug: Folfirinox
Enrollment 75
Recruitment Details Patients with pathologically confirmed, measurable or non-measurable assessable MPC or LAPC (including unresectable and borderline resectable) were recruited from November 2011 through January 2014.
Pre-assignment Details  
Arm/Group Title MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX
Hide Arm/Group Description Patients with metastatic pancreatic cancer (MPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis. Patients with locally advanced pancreatic cancer (LAPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Period Title: Overall Study
Started 44 31
Completed 37 29
Not Completed 7 2
Reason Not Completed
Withdrawal by Subject             7             2
Arm/Group Title MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX Total
Hide Arm/Group Description Patients with metastatic pancreatic cancer (MPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis. Patients with locally advanced pancreatic cancer (LAPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis. Total of all reporting groups
Overall Number of Baseline Participants 37 31 68
Hide Baseline Analysis Population Description
75 patients, including 44 with MPC and 31 with LAPC, were enrolled. The demographics and disease characteristics of the 37 evaluable patients in the MPC cohort in this study are presented here. Seven of 44 patients with MPC were excluded from efficacy analysis due to voluntary withdrawal.
Age, Customized  
Median (Full Range)
Unit of measure:  Years
Age Number Analyzed 37 participants 31 participants 68 participants
62
(50 to 77)
63
(46 to 79)
62
(46 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 31 participants 68 participants
Female
16
  43.2%
11
  35.5%
27
  39.7%
Male
21
  56.8%
20
  64.5%
41
  60.3%
ECOG Performance Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 37 participants 31 participants 68 participants
0: Fully active 17 15 32
1: Restricted in physically strenuous activity 20 16 36
Pancreatic tumour location   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 37 participants 31 participants 68 participants
Head 17 27 44
Body 14 4 18
Tumour Resection 6 0 6
[1]
Measure Description: Location of the pancreatic tumour in either the head or body of the pancreas. Six subjects had their pancreatic tumour resected (so it is no longer located in the pancreas), but still qualified for the metastatic arm.
Level of CA19.9   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 37 participants 31 participants 68 participants
Normal 4 3 7
Elevated, <59 Upper Limits of Normal 18 24 42
Elevated, >=59 Upper Limits of Normal 15 4 19
[1]
Measure Description: CA 19-9 (carbohydrate antigen 19-9 is a tumor marker that is used primarily in the management of pancreatic cancer. Changes in CA 19-9 levels help determine if the tumor is growing, remaining stable or getting smaller.
Biliary stent  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 37 participants 31 participants 68 participants
Yes 9 17 26
No 28 14 42
1.Primary Outcome
Title Progression Free Survival
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Two of 31 patients with LAPC were excluded from efficacy analysis because they did not complete four cycles to reach the first efficacy assessment (one due to cholecystitis with abscess and one due to cerebrovascular accident).
Arm/Group Title MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX
Hide Arm/Group Description:
Patients with metastatic pancreatic cancer (MPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Patients with locally advanced pancreatic cancer (LAPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Overall Number of Participants Analyzed 37 29
Measure Type: Number
Unit of Measure: percentage of participants
54 97
2.Secondary Outcome
Title Objective Response Rate
Hide Description Response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1 by independent radiology review) at 8 week intervals in patients with metastatic disease and in patients with locally advanced disease.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Two of 31 patients with LAPC were excluded from efficacy analysis because they did not complete four cycles to reach the first efficacy assessment (one due to cholecystitis with abscess and one due to cerebrovascular accident).
Arm/Group Title MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX
Hide Arm/Group Description:
Patients with metastatic pancreatic cancer (MPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Patients with locally advanced pancreatic cancer (LAPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Overall Number of Participants Analyzed 37 29
Measure Type: Number
Unit of Measure: percentage of participants
35.1 17.2
3.Secondary Outcome
Title Overall Survival
Hide Description Overall survival will be determined in patients with metastatic disease and in patients with locally advanced disease.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Two of 31 patients with LAPC were excluded from efficacy analysis because they did not complete four cycles to reach the first efficacy assessment (one due to cholecystitis with abscess and one due to cerebrovascular accident).
Arm/Group Title MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX
Hide Arm/Group Description:
Patients with metastatic pancreatic cancer (MPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Patients with locally advanced pancreatic cancer (LAPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Overall Number of Participants Analyzed 37 29
Measure Type: Number
Unit of Measure: percentage of participants
81 100
4.Secondary Outcome
Title Toxicity
Hide Description Toxicities will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) 4.0. Rates of grade 3 and 4 toxicities will be compared to historical controls. MPC and LAPC are combined because they were given the exact same medication. The study aimed to compare this dosage with historical dosage, so this comparison is the most appropriate.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
One of the total 75 patients did not receive treatment and was excluded from toxicity analysis. Treatment-related grade 3 and 4 adverse events observed in our study and in the historical control group treated with standard FOLFIRINOX.
Arm/Group Title MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX
Hide Arm/Group Description:
Patients with metastatic pancreatic cancer (MPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Patients with locally advanced pancreatic cancer (LAPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Overall Number of Participants Analyzed 43 31
Measure Type: Number
Unit of Measure: participants
Neutropenia 4 5
Thrombocytopenia 5 2
Anaemia 2 2
Febrile neutropenia 1 2
Diarrhea 8 4
Fatigue 5 4
Alanine aminotransferase (ALT) increased 3 0
Thromboembolic event 3 0
Peripheral sensory neuropathy 2 0
Vomiting 1 1
5.Secondary Outcome
Title Rate of Resection in Patients With Locally Advanced Disease
Hide Description The rate of surgical resection in the cohort of patients with locally advanced disease will be determined.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Only LAPC patients were considered in the analysis. 13 patients in the LAPC group had surgical resection. The definition of locally unresectable and borderline were clarified in the protocol.
Arm/Group Title MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX
Hide Arm/Group Description:
Patients with metastatic pancreatic cancer (MPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Patients with locally advanced pancreatic cancer (LAPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Overall Number of Participants Analyzed 0 31
Measure Type: Number
Unit of Measure: participants
Total 13
Unresectable 6
Borderline 7
6.Secondary Outcome
Title Correlate Time to Progression, Objective Response, and Overall Survival With Early Changes in Glucose Metabolism Using FDG-positron Emission Tomography (PET) Scanning
Hide Description The time to progression, objective response rate, and overall survival will be correlated with early changes in glucose metabolism using FDG-positron emission tomography (PET) scanning in patients with metastatic disease and locally advanced disease.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome was included in the 2012 protocol registration and actually describes a series of analyses that were not fully conducted, and will not be. The outcome measures described in the outcome description are presented as separated outcome measures elsewhere in this results record.
Arm/Group Title MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX
Hide Arm/Group Description:
Patients with metastatic pancreatic cancer (MPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Patients with locally advanced pancreatic cancer (LAPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse events are reported over the total duration of the study by treatment arm.
Adverse Event Reporting Description Reported below are grade 3 and 4 adverse events reported at greater than 5% per treatment arm collected. Serious Adverse Events and All Cause Mortality are reported for the overall population, while the Adverse Events are reported only for those where toxicity was assessed (1 less participant overall, see Outcome Measures).
 
Arm/Group Title MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX
Hide Arm/Group Description Patients with metastatic pancreatic cancer (MPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis. Patients with locally advanced pancreatic cancer (LAPC) were treated with modified FOLFIRINOX every 2 weeks as follows: oxaliplatin 85 mg m 2 infused over 120 min, immediately followed by folinic acid 400 mg m 2 infused over 120 min with the addition, after 30 min, of irinotecan 135 mg m 2 infused over 90 min, followed by 5FU 300 mg m 2 IV bolus, followed by 2400 mg m 2 continuous infusion for 46 h (25% reduction in bolus 5FU and irinotecan doses). All patients received pegylated filgrastim with each cycle on day 3 or 4 in the absence of severe leukocytosis. All patients routinely received palonosetron, aprepitant and dexamethasone for emesis prophylaxis.
All-Cause Mortality
MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX
Affected / at Risk (%) Affected / at Risk (%)
Total   0/44 (0.00%)   0/31 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX
Affected / at Risk (%) Affected / at Risk (%)
Total   0/44 (0.00%)   0/31 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
MPC Modified FOLFIRINOX LAPC Modified FOLFIRINOX
Affected / at Risk (%) Affected / at Risk (%)
Total   20/43 (46.51%)   11/31 (35.48%) 
Blood and lymphatic system disorders     
Neutropenia   4/43 (9.30%)  5/31 (16.13%) 
Thrombocytopenia   5/43 (11.63%)  2/31 (6.45%) 
Anaemia   2/43 (4.65%)  2/31 (6.45%) 
Febrile Neurotropenia   1/43 (2.33%)  2/31 (6.45%) 
Thromboembolic Event   3/43 (6.98%)  0/31 (0.00%) 
Gastrointestinal disorders     
Diarrhea   8/43 (18.60%)  4/31 (12.90%) 
General disorders     
Fatigue   5/43 (11.63%)  4/31 (12.90%) 
Alanine aminotransferase   3/43 (6.98%)  0/31 (0.00%) 
Nervous system disorders     
Peripheral sensory neuropathy   2/43 (4.65%)  0/31 (0.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jill Lacy
Organization: Yale University
Phone: +1 (203) 737-1600
EMail: jill.lacy@yale.edu
Layout table for additonal information
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01523457     History of Changes
Other Study ID Numbers: 1108008901
First Submitted: January 23, 2012
First Posted: February 1, 2012
Results First Submitted: September 1, 2016
Results First Posted: August 30, 2017
Last Update Posted: August 30, 2017