Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer

Pancreatic Cancer Clinical Trial

— FOLFIRINOX  

Official title:

Phase II Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01523457
• Other study ID #: 1108008901
• Status: Completed
• Phase: Phase 2
• First received: January 23, 2012
• Last updated: August 28, 2017
• Start date: October 2011
• Est. completion date: December 2015

Study information

• Verified date: May 2017
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: December 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Pancreatic Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	Smilow Cancer Center	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Overall Survival	Overall survival will be determined in patients with metastatic disease and in patients with locally advanced disease.	24 weeks
Secondary	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
Secondary	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
Secondary	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