Back to resultsStudy of Modified FOLFIRINOX in Advanced Pancreatic Cancer (FOLFIRINOX)
Primary Purpose
Metastatic Pancreatic Cancer, Pancreatic Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Folfirinox
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Pancreatic Cancer focused on measuring metastatic pancreatic cancer, locally advanced pancreatic cancer, FOLFIRINOX, phase II, progression free survival
Eligibility Criteria
Inclusion Criteria:
- Pathologic or cytologic documentation of pancreatic adenocarcinoma
- Metastatic or locally advanced unresectable disease, including borderline unresectable disease
- Patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting chemoradiation
- Measurable or non-measurable assessable disease
- No prior treatment (chemotherapy, biological therapy, or radiotherapy) for metastatic or non-metastatic locally advanced unresectable pancreatic cancer
- 6 months since completion of any prior neoadjuvant or adjuvant therapy (chemotherapy or radiotherapy) for resected pancreatic cancer
- No prior treatment with oxaliplatin or irinotecan
- No prior treatment with fluoruouracil or capecitabine unless administered as a radiosensitizing drug during adjuvant/neoadjuvant chemoradiotherapy after/before resection of pancreatic cancer
- Patients who received chemotherapy > 2 years ago for malignancies other than pancreatic cancer are eligible, provided that chemotherapy was completed > 2 years ago and there is no evidence of the second malignancy at the time of study entry
- > 4 weeks since major surgery
- No other concurrent anticancer therapy
- ECOG Performance Status: 0-1
- Age > 18
- No other malignancy within past two years except basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer
- Paraffin block or slides must be available
- Adequate organ function
- No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
- No > grade 1 sensory peripheral neuropathy
- No uncontrolled seizure disorder, active neurological disease, or known CNS disease
- No significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment
- No history of chronic diarrhea
- Not pregnant and not nursing
- No other medical condition or reason that, in the opinion of the investigator, would preclude study participation
- Laboratory parameters as follows: absolute neutrophil count ≥ 1,500/uL, platelet count ≥ 100,000/uL, hemoglobin ≥ 9 g,/dL, creatinine < 1.5 X ULN or estimated GFR > 30 ml/min, bilirubin < 1.5 X ULN, AST and ALT < 3 X ULN, negative pregnancy test in women of childbearing age
Sites / Locations
- Smilow Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
MPC modified FOLFIRINOX
LAPC modified FOLFIRINOX
Arm 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.
Outcomes
Primary Outcome Measures
Progression Free Survival
The primary objective of this study is to determine the progression free survival in patients with metastatic pancreatic cancer and in patients with locally advanced unresectable non-metastatic pancreatic cancer treated with a dose-attenuated modification of FOLFIRINOX. Tumour response was determined according to RECIST 1.1 by independent radiology review.
Secondary Outcome Measures
Objective Response Rate
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.
Overall Survival
Overall survival will be determined in patients with metastatic disease and in patients with locally advanced disease.
Toxicity
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.
Rate of Resection in Patients With Locally Advanced Disease
The rate of surgical resection in the cohort of patients with locally advanced disease will be determined.
Correlate Time to Progression, Objective Response, and Overall Survival With Early Changes in Glucose Metabolism Using FDG-positron Emission Tomography (PET) Scanning
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01523457
Brief Title
Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer
Acronym
FOLFIRINOX
Official Title
Phase II Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study was to determine the progression free survival in patients with metastatic pancreatic cancer and in patients with locally advanced unresectable non-metastatic pancreatic cancer treated with a dose-attenuated modification of folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX). Secondary endpoints included: determine objective response rate according to RECIST; determine overall survival; evaluate toxicity; determine rate of resection in locally advanced unresectable stratum; correlate time to progression, objective response, and overall survival with early changes in glucose metabolism using [18F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scanning.
Detailed Description
A phase II open label single arm multi-institutional study at Yale's Smilow Cancer Hospital (New Haven, CT, USA), the Smilow Cancer Hospital Care Centers (regional community-based clinics), the VA Connecticut Healthcare System West Haven Campus (West Haven, CT, USA) and Bridgeport Hospital (Bridgeport, CT, USA). The primary objective of this study was to determine the PFS in patients with MPC and LAPC treated with a dose attenuated modification of FOLFIRINOX.
NOTE: Upon results reporting (2016), the registration record was reorganized to display MPC and LAPC groups in individual arms. The most meaningful comparison is between MPC/LAPC and historical controls. That is how results are reported in the published paper, see citations.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Cancer, Pancreatic Cancer
Keywords
metastatic pancreatic cancer, locally advanced pancreatic cancer, FOLFIRINOX, phase II, progression free survival
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MPC modified FOLFIRINOX
Arm Type
Experimental
Arm 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.
Arm Title
LAPC modified FOLFIRINOX
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Folfirinox
Intervention Description
Oxaliplatin 85 mg/m2 IV infused over two hours, followed by
Leucovorin 400 mg/m2 IV over two hours
Irinotecan 135 mg/m2 IV over 90 minutes (concurrent with leucovorin during the last 90 min of the leucovorin infusion)
5-FU 300mg/m2 IV bolus, then 2400 mg/m2 continuous IV infusion over 46 hours
FOLFIRINOX is a chemotherapy regimen. It is made up of the following four drugs:
FOL - folinic acid (leucovorin), a vitamin B derivative that modulates/potentiates/reduces the side effects of fluorouracil; F - fluorouracil (5-FU), a pyrimidine analog and antimetabolite which incorporates into the DNA molecule and stops DNA synthesis; IRIN - irinotecan (Camptosar), a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating; and OX - oxaliplatin (Eloxatin), a platinum-based antineoplastic agent, which inhibits DNA repair and/or DNA synthesis.
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
The primary objective of this study is to determine the progression free survival in patients with metastatic pancreatic cancer and in patients with locally advanced unresectable non-metastatic pancreatic cancer treated with a dose-attenuated modification of FOLFIRINOX. Tumour response was determined according to RECIST 1.1 by independent radiology review.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Objective Response Rate
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
Title
Overall Survival
Description
Overall survival will be determined in patients with metastatic disease and in patients with locally advanced disease.
Time Frame
24 weeks
Title
Toxicity
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
Title
Rate of Resection in Patients With Locally Advanced Disease
Description
The rate of surgical resection in the cohort of patients with locally advanced disease will be determined.
Time Frame
24 weeks
Title
Correlate Time to Progression, Objective Response, and Overall Survival With Early Changes in Glucose Metabolism Using FDG-positron Emission Tomography (PET) Scanning
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathologic or cytologic documentation of pancreatic adenocarcinoma
Metastatic or locally advanced unresectable disease, including borderline unresectable disease
Patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting chemoradiation
Measurable or non-measurable assessable disease
No prior treatment (chemotherapy, biological therapy, or radiotherapy) for metastatic or non-metastatic locally advanced unresectable pancreatic cancer
6 months since completion of any prior neoadjuvant or adjuvant therapy (chemotherapy or radiotherapy) for resected pancreatic cancer
No prior treatment with oxaliplatin or irinotecan
No prior treatment with fluoruouracil or capecitabine unless administered as a radiosensitizing drug during adjuvant/neoadjuvant chemoradiotherapy after/before resection of pancreatic cancer
Patients who received chemotherapy > 2 years ago for malignancies other than pancreatic cancer are eligible, provided that chemotherapy was completed > 2 years ago and there is no evidence of the second malignancy at the time of study entry
> 4 weeks since major surgery
No other concurrent anticancer therapy
ECOG Performance Status: 0-1
Age > 18
No other malignancy within past two years except basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer
Paraffin block or slides must be available
Adequate organ function
No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
No > grade 1 sensory peripheral neuropathy
No uncontrolled seizure disorder, active neurological disease, or known CNS disease
No significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment
No history of chronic diarrhea
Not pregnant and not nursing
No other medical condition or reason that, in the opinion of the investigator, would preclude study participation
Laboratory parameters as follows: absolute neutrophil count ≥ 1,500/uL, platelet count ≥ 100,000/uL, hemoglobin ≥ 9 g,/dL, creatinine < 1.5 X ULN or estimated GFR > 30 ml/min, bilirubin < 1.5 X ULN, AST and ALT < 3 X ULN, negative pregnancy test in women of childbearing age
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jill Lacy, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Smilow Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27022826
Citation
Stein SM, James ES, Deng Y, Cong X, Kortmansky JS, Li J, Staugaard C, Indukala D, Boustani AM, Patel V, Cha CH, Salem RR, Chang B, Hochster HS, Lacy J. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Br J Cancer. 2016 Mar 29;114(7):737-43. doi: 10.1038/bjc.2016.45.
Results Reference
result
Learn more about this trial
Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer
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