Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UC Davis UC Irvine UCSD
Dates
study started

Description

Summary

This randomized phase II trial studies how well combination chemotherapy (mFOLFIRINOX) with or without hypofractionated radiation therapy before surgery works in patients with pancreatic cancer that can be removed by surgery. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. It is not yet known if combination chemotherapy is more effective with or without hypofractionated radiation therapy before surgery in treating patients with pancreatic cancer.

Official Title

Preoperative Extended Chemotherapy vs. Chemotherapy Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Head of the Pancreas

Details

PRIMARY OBJECTIVES:

  1. To evaluate and estimate 18 months overall survival (OS) rate of patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) receiving neoadjuvant therapy.

SECONDARY OBJECTIVES:

  1. To evaluate and estimate the R0 resection rates in patients receiving each of the two multimodality treatment regimens.

II. To evaluate and estimate the event-free survival in patients receiving each of the two multimodality treatment regimens.

III. To evaluate and estimate the pathologic compete response (pCR) rates in patients receiving each of the two multimodality treatment regimens.

IV. To assess the adverse events (AE) profile and safety of each treatment arm.

TERTIARY OBJECTIVES:

  1. To test the effect of the rs2853564 vitamin D receptor (VDR) variant on OS rate and discover novel candidate genes associated with OS and severe toxicity of chemotherapy by using genome-wide genotyping approaches.

II. To evaluate risk classification previously developed by Koay et al using normalized area under the enhancement curve (NAUC).

III. To access prognostic value of NAUC ratio defined as post-neoadjuvant NAUC divided by pre-neoadjuvant therapy NAUC.

IV. To evaluate risk classification previously developed by Koay et al using delta measure.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 8 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive either stereotactic body radiation therapy (SBRT) or hypofractionated image guided radiation therapy (HIGRT) on days 1-5 of course 8.

SURGERY Within 4 to 8 weeks after the last dose of chemotherapy (arm A) or of radiation (arm B), patients considered surgical candidates for resection (after central review) will undergo surgery at the registering institution.

ADJUVANT CHEMOTHERAPY Within 4-12 weeks from the date of surgery, patients will receive oxaliplatin IV over 2 hours and leucovorin IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 16 weeks for 2 years, then every 6 months for 5 years.

Keywords

Pancreatic Adenocarcinoma, Borderline Resectable Adenocarcinoma of the Head of the Pancrease, Adenocarcinoma, radiation therapy, surgery, mFOLFIRINOX, FOLFOX, mFOLFIRINOX + surgery + FOLFOX, mFOLFIRINOX + radiation + surgery + FOLFOX

Eligibility

For people ages 18 years and up

Inclusion Criteria:

  • Confirmation of radiographic stage as borderline resectable disease by real-time Alliance central radiographic review
  • No prior chemotherapy or radiation for pancreatic cancer
  • No definitive resection of pancreatic cancer
  • Chronic concomitant treatment with strong inhibitors of cytochrome p450, family 3, subfamily a, polypeptide 4 gene (CYP3A4) is not allowed on this study; patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study
  • Chronic concomitant treatment with strong CYP3A4 inducers is not allowed; patients must discontinue the drug 14 days prior to the start of study treatment
  • No grade >= 2 neuropathy
  • No known Gilbert's syndrome or known homozygosity for UGAT1A1*28 polymorphism
  • No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease) within 28 days of registration
  • Not pregnant and not nursing; for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Absolute neutrophil count (ANC) >= 1,500/mm3
  • Platelet count >= 100,000/mm3
  • Creatinine =< 1.5 x upper limit of normal (ULN) or
  • Calculated (calc.) creatinine clearance > 45 mL/min
  • Total bilirubin =< 2.0 mg/dL
  • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 X upper limit of normal (ULN)

Locations

  • UC San Diego Moores Cancer Center
    La Jolla California 92093 United States
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
    Orange California 92868 United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento California 95817 United States
  • California Pacific Medical Center-Pacific Campus
    San Francisco California 94115 United States
  • Kaiser Permanente-San Francisco
    San Francisco California 94115 United States
  • University Oncology Associates
    Clovis California 93611 United States
  • Kaiser Permanente-Fresno
    Fresno California 93720 United States
  • Kaiser Permanente-South San Francisco
    South San Francisco California 94080 United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley California 94704 United States
  • Los Angeles County-USC Medical Center
    Los Angeles California 90033 United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
Alliance for Clinical Trials in Oncology
ID
NCT02839343
Phase
Phase 2 Pancreatic Cancer Research Study
Study Type
Interventional
Participants
About 126 people participating
Last Updated