Study Of Modified FOLFIRINOX In Advanced Pancreatic Cancer

Study Overview

Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer

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.

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.

Metastatic Pancreatic Cancer
Pancreatic Cancer

DRUG: Folfirinox

1108008901

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2012-01-23	Results First Submitted 2016-09-01	Last Update Submitted that met QC Criteria 2017-08-28
First Submitted that Met QC Criteria 2012-01-31	Results First Submitted that Met QC Criteria 2017-08-28	Last Update Posted (ACTUAL) 2017-08-30
First Posted (ACTUAL) 2012-02-01	Results First Posted 2017-08-30	Last Verified 2017-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/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 m	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
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, aft	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

Participant Group/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 m

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

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, aft

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

Primary Outcome Measures	Measure Description	Time Frame
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.	24 weeks

Secondary Outcome Measures	Measure Description	Time Frame
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.	24 weeks
Overall Survival	Overall survival will be determined in patients with metastatic disease and in patients with locally advanced disease.	24 weeks
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.	24 weeks
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.	24 weeks
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.	24 weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Jill Lacy, MD, Yale University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

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