Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01523457
• Collaborator: (none)
• Enrollment: 75
• Location: 1
• Arms: 2
• Duration (Months): 50
• Patients Per Site Per Month: 1.5

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Cancer; Pancreatic Cancer	Drug: Folfirinox	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MPC modified FOLFIRINOX 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.	Drug: Folfirinox; 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.
Experimental: LAPC modified FOLFIRINOX 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.	Drug: Folfirinox; 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.

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [24 weeks]

   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

1. Objective Response Rate [24 weeks]

   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.

2. Overall Survival [24 weeks]

   Overall survival will be determined in patients with metastatic disease and in patients with locally advanced disease.

3. Toxicity [24 weeks]

   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.

4. Rate of Resection in Patients With Locally Advanced Disease [24 weeks]

   The rate of surgical resection in the cohort of patients with locally advanced disease will be determined.

5. Correlate Time to Progression, Objective Response, and Overall Survival With Early Changes in Glucose Metabolism Using FDG-positron Emission Tomography (PET) Scanning [24 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Smilow Cancer Center	New Haven	Connecticut	United States	06510

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Jill Lacy, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT01523457
• Other Study ID Numbers: 1108008901
• First Posted: Feb 1, 2012
• Last Update Posted: Aug 30, 2017
• Last Verified: May 1, 2017

• Keywords provided by Yale University: metastatic pancreatic cancer; locally advanced pancreatic cancer; FOLFIRINOX; phase II; progression free survival
• Additional relevant MeSH terms: Pancreatic Neoplasms; Folfirinox

Study Results

Participant Flow

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.

Arm/Group Title	MPC Modified FOLFIRINOX	LAPC Modified FOLFIRINOX
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

Baseline Characteristics

Arm/Group Title	MPC Modified FOLFIRINOX	LAPC Modified FOLFIRINOX	Total
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 Participants	37	31	68
Age, Customized (years) [Median (Full Range) ]
Age	62	63	62
Sex: Female, Male (Count of Participants)
Female	16 43.2%	11 35.5%	27 39.7%
Male	21 56.8%	20 64.5%	41 60.3%
ECOG Performance Status (participants) [Number]
0: Fully active	17 45.9%	15 48.4%	32 47.1%
1: Restricted in physically strenuous activity	20 54.1%	16 51.6%	36 52.9%
Pancreatic tumour location (participants) [Number]
Head	17 45.9%	27 87.1%	44 64.7%
Body	14 37.8%	4 12.9%	18 26.5%
Tumour Resection	6 16.2%	0 0%	6 8.8%
Level of CA19.9 (participants) [Number]
Normal	4 10.8%	3 9.7%	7 10.3%
Elevated, <59 Upper Limits of Normal	18 48.6%	24 77.4%	42 61.8%
Elevated, >=59 Upper Limits of Normal	15 40.5%	4 12.9%	19 27.9%
Biliary stent (participants) [Number]
Yes	9 24.3%	17 54.8%	26 38.2%
No	28 75.7%	14 45.2%	42 61.8%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

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
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.
Measure Participants	37	29
Number [percentage of participants]	54 145.9%	97 312.9%

2. Secondary Outcome

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

Outcome Measure Data

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
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.
Measure Participants	37	29
Number [percentage of participants]	35.1 94.9%	17.2 55.5%

3. Secondary Outcome

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

Outcome Measure Data

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
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.
Measure Participants	37	29
Number [percentage of participants]	81 218.9%	100 322.6%

4. Secondary Outcome

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

Outcome Measure Data

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
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.
Measure Participants	43	31
Neutropenia	4 10.8%	5 16.1%
Thrombocytopenia	5 13.5%	2 6.5%
Anaemia	2 5.4%	2 6.5%
Febrile neutropenia	1 2.7%	2 6.5%
Diarrhea	8 21.6%	4 12.9%
Fatigue	5 13.5%	4 12.9%
Alanine aminotransferase (ALT) increased	3 8.1%	0 0%
Thromboembolic event	3 8.1%	0 0%
Peripheral sensory neuropathy	2 5.4%	0 0%
Vomiting	1 2.7%	1 3.2%

5. Secondary Outcome

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

Outcome Measure Data

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
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.
Measure Participants	0	31
Total	13 35.1%
Unresectable	6 16.2%
Borderline	7 18.9%

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
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

Outcome Measure Data

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
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.
Measure Participants	0	0

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/31 (0%)
Serious Adverse Events
	MPC Modified FOLFIRINOX		LAPC Modified FOLFIRINOX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	MPC Modified FOLFIRINOX		LAPC Modified FOLFIRINOX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/43 (46.5%)		11/31 (35.5%)
Blood and lymphatic system disorders
Neutropenia	4/43 (9.3%)		5/31 (16.1%)
Thrombocytopenia	5/43 (11.6%)		2/31 (6.5%)
Anaemia	2/43 (4.7%)		2/31 (6.5%)
Febrile Neurotropenia	1/43 (2.3%)		2/31 (6.5%)
Thromboembolic Event	3/43 (7%)		0/31 (0%)
Gastrointestinal disorders
Diarrhea	8/43 (18.6%)		4/31 (12.9%)
General disorders
Fatigue	5/43 (11.6%)		4/31 (12.9%)
Alanine aminotransferase	3/43 (7%)		0/31 (0%)
Nervous system disorders
Peripheral sensory neuropathy	2/43 (4.7%)		0/31 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.