Combination Chemotherapy with or without Stereotactic Body Radiation Therapy in Treating Patients with Locally Advanced Pancreatic Cancer That Cannot Be Removed by Surgery

Status: Active

Description

This randomized phase III trial studies combination chemotherapy and stereotactic body radiation therapy to see how well they work compared to combination chemotherapy alone in treating patients with pancreatic cancer that has spread from where it started to nearby tissue or lymph nodes and cannot be removed by surgery. Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, leucovorin calcium, 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. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. It is not yet known whether combination chemotherapy is more effective with or without stereotactic body radiation therapy in treating patients with pancreatic cancer.

Eligibility Criteria

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 following induction mFOLFIRINOX
  • Typically, pancreatic tumors must be less than 8.0 cm in greatest axial dimension at the time of treatment planning but final determination of eligibility will be based upon satisfying the radiation normal tissue constraints
  • No prior systemic therapy EXCEPT patients may be consented and enrolled if they have already started mFOLFIRINOX for up to four cycles
  • Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2
  • Within 30 days of eligibility confirmation: Leukocytes (white blood cells [WBC]) >= 3,000/uL
  • Within 30 days of eligibility confirmation: Absolute neutrophil count (ANC) >= 1,500 uL
  • Within 30 days of eligibility confirmation: Platelets >= 50,000/uL
  • Within 30 days of eligibility confirmation: Total bilirubin =< 1.5 X institutional upper limit of normal
  • Within 30 days of eligibility confirmation: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Within 30 days of eligibility confirmation: Creatinine not above the upper limit of 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
  • Patients who have received chemotherapy for pancreatic cancer, other than up to 4 cycles of mFOLFIRINOX as noted above
  • Uncontrolled 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, or 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 and breastfeeding women are excluded; as well as 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) to avoid pregnancy for the duration of the study; male subjects must also agree to use effective contraception for the same period as above; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Women who are not post-menopausal and have a positive urine or serum pregnancy test or refuse to take a pregnancy test

Locations & Contacts

California

Palo Alto
Stanford Cancer Institute Palo Alto
Status: Active
Contact: Daniel T. Chang
Phone: 650-724-1901
Email: dtchang@stanford.edu

Illinois

Maywood
Loyola University Medical Center
Status: Active
Contact: Tarita O. Thomas
Phone: 708-216-2587
Email: tathomas@lumc.edu

South Carolina

Charleston
Medical University of South Carolina
Status: Active
Contact: David T. Marshall
Phone: 843-792-3273
Email: marshadt@musc.edu

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: Jeffrey John Meyer
Phone: 214-645-7604
Email: Jeffrey.Meyer@UTSouthwestern.edu
Houston
M D Anderson Cancer Center
Status: Active
Contact: Albert Ching-Wei Koong
Phone: 713-563-2300
Email: akong@mdanderson.org

Washington

Seattle
Swedish Medical Center-First Hill
Status: Approved
Contact: Vivek Krishan Mehta
Email: Vivek.Mehta@swedish.org

Ontario

Toronto
University Health Network-Princess Margaret Hospital
Status: Active
Contact: Laura Ann Dawson
Phone: 416-946-2127
Email: Laura.Dawson@rmp.uhn.on.ca

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To compare the median progression-free survival between arm 1 (modified fluorouracil, oxaliplatin, leucovorin calcium, and irinotecan hydrochloride [mFOLFIRINOX]) vs arm 2 (mFOLFIRINOX + stereotactic body radiation therapy [SBRT]).

SECONDARY OBJECTIVES:

I. To compare metastasis free survival for pancreatic patients following chemotherapy +/- SBRT.

II. To compare 1 year progression-free survival in pancreatic patients following chemotherapy +/- SBRT.

III. To compare local progression-free survival in pancreatic patients after chemotherapy +/- SBRT.

IV. To compare the overall survival in pancreatic cancer patients following chemotherapy +/- SBRT.

V. To evaluate acute (within 3 months of treatment) grade 2 or greater fistula, perforation, ulcer or other grade 3-4 acute gastrointestinal toxicities for the chemotherapy + SBRT arm.

VI. To identify new biomarkers in pancreatic cancer.

VII. To evaluate the quality of life of patients before and after therapy for patients treated with chemotherapy +/- SBRT.

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

ARM I:

INDUCTION THERAPY: Patients receive mFOLFIRINOX comprising oxaliplatin intravenously (IV) over 2 hours on day 1, irinotecan hydrochloride IV over 90 minutes on day 1, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-2. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

SBRT: Beginning approximately 8 weeks after completion of induction chemotherapy, patients undergo SBRT once daily (QD) for a total of 5 fractions. SBRT should be delivered over a 5-day period; however, SBRT may be delivered over 2 weeks, as long as patients receive at least 2 fractions per week.

MAINTENANCE THERAPY: Beginning approximately 8 weeks after completion of SBRT, patients continue mFOLFIRINOX.

ARM II: Patients receive mFOLFIRINOX comprising oxaliplatin, irinotecan hydrochloride, leucovorin calcium, and fluorouracil as in Arm I.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for up to 2 years.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Stanford Cancer Institute Palo Alto

Principal Investigator
Daniel T. Chang

Trial IDs

Primary ID PANC0015
Secondary IDs NCI-2013-01658, 5136
Clinicaltrials.gov ID NCT01926197