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

A Randomized Phase III Study Evaluating Modified FOLFIRINOX (mFFX) With or Without Stereotactic Body Radiotherapy (SBRT) in the Treatment of Locally Advanced Pancreatic Cancer: A Pancreatic Cancer Radiotherapy Study Group (PanCRS) Trial

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin; Drug: 5FU; Radiation: Stereotactic Body Radiotherapy (SBRT)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency
  • Ontario
    • Toronto, Ontario, Canada
      • Princess Margaret Cancer Centre
• United States
  • California
    • Los Angeles, California, United States, 60153
      • UCLA
    • San Francisco, California, United States, 94143
      • UCSF
    • Stanford, California, United States, 94305
      • Stanford University, School of Medicine
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
  • Washington
    • Seattle, Washington, United States, 98107
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

• 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

EXCLUSION CRITERIA

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

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.; Other Names: Eloxatin; Drug: Irinotecan; Irinotecan 180 mg/m² IV over 90 minutes on Day 1 of a 14-day cycle.; Other Names: Campto; Camptosar; Onivyde; Camptothecin-11 (CPT-11); Drug: Leucovorin; Leucovorin 400 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.; Other Names: Wellcovorin; Citrovorum Factor; Folinic acid; Drug: 5FU; 5FU 2,400 mg/m² IV over 46 to 48 hours starting on Day 1 of a 14-day cycle.; Other Names: 5-fluorouracil; Carac; Adrucil; Efudex; Fluoroplex; Tolak
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.; Other Names: Eloxatin; Drug: Irinotecan; Irinotecan 180 mg/m² IV over 90 minutes on Day 1 of a 14-day cycle.; Other Names: Campto; Camptosar; Onivyde; Camptothecin-11 (CPT-11); Drug: Leucovorin; Leucovorin 400 mg/m² IV over 2 hours on Day 1 of a 14-day cycle.; Other Names: Wellcovorin; Citrovorum Factor; Folinic acid; Drug: 5FU; 5FU 2,400 mg/m² IV over 46 to 48 hours starting on Day 1 of a 14-day cycle.; Other Names: 5-fluorouracil; Carac; Adrucil; Efudex; Fluoroplex; Tolak; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2013
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: August 15, 2013
• First Submitted That Met QC Criteria: August 16, 2013
• First Posted (Estimate): August 20, 2013

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Camptothecin
• Other Study ID Numbers: IRB-27492; PANC0015 (Other Identifier: OnCore); NCI-2013-01658 (Other Identifier: NCI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No