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.

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.

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