Phase 3 Study Of FOLFIRINOX (mFFX) +/- SBRT In Locally Advanced Pancreatic Cancer

Study Overview

Phase 3 Study of FOLFIRINOX (mFFX) +/- SBRT in Locally Advanced Pancreatic Cancer

The goal of this study is to determine the safety and efficacy of a chemotherapy regimen known as Modified FOLFIRINOX (mFFX) alone or with the addition of Stereotactic Body Radiotherapy (SBRT). We hope to learn if this new treatment combination helps to control the disease and improve survival for patients with locally advanced pancreatic cancer.

Primary Objective: To determine progression free survival for mFFX +/- SBRT. Secondary Objectives: * To determine metastasis free survival following mFFX chemotherapy alone or with SBRT. * To determine the overall survival in pancreatic cancer patients treated with chemotherapy +/- SBRT. * To determine local progression-free survival in pancreatic cancer patients after chemotherapy +/- SBRT. * To evaluate acute (within 3 months of treatment) grade 2 or greater gastritis, fistula, enteritis, or ulcer and any other grade 3-4 gastrointestinal toxicity within 3 months of treatment. * To evaluate the utility of FDG-PET for treatment planning and estimation of progression free survival. * To identify new biomarkers in pancreatic cancer. * To evaluate the quality of life of patients before and after either chemotherapy or chemotherapy and SBRT.

Pancreatic Cancer

DRUG: Oxaliplatin
DRUG: Irinotecan
DRUG: Leucovorin
DRUG: 5FU
RADIATION: Stereotactic Body Radiotherapy (SBRT)

IRB-27492
PANC0015 (OTHER Identifier) (OTHER: OnCore)
NCI-2013-01658 (OTHER Identifier) (OTHER: NCI)

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 2013-08-15	Results First Submitted 2022-10-03	Last Update Submitted that met QC Criteria 2022-10-03
First Submitted that Met QC Criteria 2013-08-16	Results First Submitted that Met QC Criteria 2022-10-03	Last Update Posted (ACTUAL) 2022-10-28
First Posted (ACTUAL) 2013-08-20	Results First Posted 2022-10-28	Last Verified 2022-10

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:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
ACTIVE_COMPARATOR: Modified FOLFIRINOX Modified FOLFIRINOX (mFFX), a chemotherapeutic treatment regimen of 5FU, leucovorin, irinotecan, and oxaliplatin.	DRUG: Oxaliplatin Oxaliplatin 85 mg/m² IV over 2 hours on Day 1 of a 14-day cycle. DRUG: Irinotecan Irinotecan 180 mg/m² IV over 90 minutes on Day 1 of a 14-day cycle. DRUG: Leucovorin Leucovorin 400 mg/m² IV over 2 hours on Day 1 of a 14-day cycle. DRUG: 5FU 5FU 2,400 mg/m² IV over 46 to 48 hours starting on Day 1 of a 14-day cycle. RADIATION: Stereotactic Body Radiotherapy (SBRT) Radiotherapy treatment starting about 8 weeks after modified FOLFIRINOX induction chemotherapy, administered as 5 fractions of 8 Grey (Gy) each, on 5 separate days.
EXPERIMENTAL: Modified FOLFIRINOX plus Stereotactic Body Radiotherapy Modified FOLFIRINOX (mFFX), a chemotherapeutic treatment regimen of 5FU, leucovorin, irinotecan, and oxaliplatin, in combination with stereotactic body radiotherapy (SBRT)	DRUG: Oxaliplatin Oxaliplatin 85 mg/m² IV over 2 hours on Day 1 of a 14-day cycle. DRUG: Irinotecan Irinotecan 180 mg/m² IV over 90 minutes on Day 1 of a 14-day cycle. DRUG: Leucovorin Leucovorin 400 mg/m² IV over 2 hours on Day 1 of a 14-day cycle. DRUG: 5FU 5FU 2,400 mg/m² IV over 46 to 48 hours starting on Day 1 of a 14-day cycle. RADIATION: Stereotactic Body Radiotherapy (SBRT) Radiotherapy treatment starting about 8 weeks after modified FOLFIRINOX induction chemotherapy, administered as 5 fractions of 8 Grey (Gy) each, on 5 separate days.

Participant Group/Arm

Intervention/Treatment

ACTIVE_COMPARATOR: Modified FOLFIRINOX

Modified FOLFIRINOX (mFFX), a chemotherapeutic treatment regimen of 5FU, leucovorin, irinotecan, and oxaliplatin.

DRUG: Oxaliplatin

Oxaliplatin 85 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.

DRUG: Irinotecan

Irinotecan 180 mg/m² IV over 90 minutes on Day 1 of a 14-day cycle.

DRUG: Leucovorin

Leucovorin 400 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.

DRUG: 5FU

5FU 2,400 mg/m² IV over 46 to 48 hours starting on Day 1 of a 14-day cycle.

RADIATION: Stereotactic Body Radiotherapy (SBRT)

Radiotherapy treatment starting about 8 weeks after modified FOLFIRINOX induction chemotherapy, administered as 5 fractions of 8 Grey (Gy) each, on 5 separate days.

EXPERIMENTAL: Modified FOLFIRINOX plus Stereotactic Body Radiotherapy

Modified FOLFIRINOX (mFFX), a chemotherapeutic treatment regimen of 5FU, leucovorin, irinotecan, and oxaliplatin, in combination with stereotactic body radiotherapy (SBRT)

DRUG: Oxaliplatin

Oxaliplatin 85 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.

DRUG: Irinotecan

Irinotecan 180 mg/m² IV over 90 minutes on Day 1 of a 14-day cycle.

DRUG: Leucovorin

Leucovorin 400 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.

DRUG: 5FU

5FU 2,400 mg/m² IV over 46 to 48 hours starting on Day 1 of a 14-day cycle.

RADIATION: Stereotactic Body Radiotherapy (SBRT)

Radiotherapy treatment starting about 8 weeks after modified FOLFIRINOX induction chemotherapy, administered as 5 fractions of 8 Grey (Gy) each, on 5 separate days.

Primary Outcome Measures	Measure Description	Time Frame
Progression-free Survival (PFS)	Progression-free survival (PFS) means the period of time that a participant remains alive without tumor progression either locally or at a distant site in the body (metastasis). The effect of the study treatments was assessed as the median PFS of participants in the treatment groups. The outcome is reported as the median PFS with standard deviation.	38 months

Secondary Outcome Measures	Measure Description	Time Frame
Local Progression-free Survival (Local PFS)	Local progression-free survival (PFS) means the period of time that a participant remains alive without recurrence or advancement of the disease at the baseline sites of the tumor (local progression). The effect of the study treatments was assessed as the median local PFS of participants in the treatment groups. The outcome is reported as the median local PFS with standard deviation.	38 months
Progression-free Survival (PFS) at 1 Year	Progression-free survival (PFS) means the period of time that a participant remains alive without tumor progression either locally or at a distant site in the body (metastasis). The effect of the study treatments was assessed as the number of participants in each treatment group that remained alive without tumor progression, at 1 year after treatment. The outcome is reported as a number without dispersion.	1 year
Metastasis-free Survival (MFS)	Metastasis-free survival (MFS) means the period of time that a participant remains alive without the appearance of new tumor lesions a distant site in the body (metastasis). The effect of the study treatments was assessed as the median MFS of participants in the treatment groups. The outcome is reported as the median PFS with standard deviation.	62 months
Overall Survival (OS)	The effect of the study treatments was assessed as the length of time participants in each treatment group that remained alive. The outcome is reported as the median OS with standard deviation.	62 months
Grade 2 or Greater Gastrointestinal (GI) Toxicity	Toxicity means an adverse event related to the study treatment. Toxicity was assessed between treatment groups as the number of treatment-related , ≥ grade 2 events of gastritis, fistula, enteritis, or ulcer; plus any other Grade 3 to 5 gastrointestinal (GI) toxicity. The outcome is reported as the number of defined adverse events by preferred term for each treatment group, occurring within 3 months of the start of treatment. These adverse events by definition are all within the Common Terminology Criteria for Adverse Events (CTCAE) version 4.01 Gastrointestinal Body System. The outcome is reported as numbers without dispersion. All-cause Mortality mFFX 7 SBRT 8	3 months

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:

Histologically-confirmed adenocarcinoma of the pancreas
Determined unresectable by a pancreatic cancer surgeon or a multi-disciplinary or gastrointestinal oncology Tumor Board.
Stable or better disease on re-staging scans
Typically, tumors < 8.0 cm in greatest axial dimension but final determination of eligibility based upon radiation normal tissue constraints
Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2
Leukocytes (white blood cells, WBC) ≥ 3,000/mL
Absolute neutrophil count (ANC) ≥ 1,500/mL
Platelets ≥ 50,000/mL
Total bilirubin ≤ 1.5 X institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 X institutional ULN
Creatinine within normal institutional limits
Ability to understand and the willingness to sign an informed consent form
Life expectancy > 6 months

Metastatic disease
Prior radiotherapy to the upper abdomen/liver.
Prior chemotherapy for pancreatic cancer, other than up to 4 cycles of modified FOLFIRINOX.
Age < 18 years
Uncontrolled intercurrent illness including, but not limited to:

Ongoing or active infection (or infections requiring systemic antibiotic treatment)
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
Psychiatric illness/social situations that would limit compliance with study requirements.
Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, or carcinoma in situ of the cervix. Patients with a previous malignancy without evidence of disease for > 5 years will be allowed to enter the trial.
Pregnant or lactating
Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control (hormonal or barrier method of birth control; abstinence) for duration of the study
Women who are not post-menopausal (as defined in Appendix III) and have a positive urine or serum pregnancy test or refuse to take a pregnancy test
Male subjects who are unwilling or unable to use effective contraception for duration of the study

Collaborators and Investigators

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

Investigators

PRINCIPAL_INVESTIGATOR: Daniel T Chang, Stanford 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

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