Combination Chemotherapy before and after Surgery in Treating Patients with Resectable Pancreatic Cancer
This phase I trial studies how well combination chemotherapy before and after surgery works in treating patients with pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, 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.
Inclusion Criteria
- Histologic or cytologic diagnosis of adenocarcinoma of the pancreas
- Resectable primary tumor of the head, body or tail of the pancreas defined per National Comprehensive Cancer Network (NCCN) guidelines version 2.2015: * No extra-pancreatic disease, aside from lymphadenopathy * No arterial tumor contact (celiac axis, superior mesenteric artery, or common hepatic artery) * No tumor contact with the superior mesenteric vein or portal vein or =< 180 degree contact without vein contour irregularity
- Confirmation of resectability by surgical oncology consultation
- No previous therapy for pancreatic cancer
- Short removable metal stents rather than plastic stents are strongly encouraged but not required for palliation of initial obstructive jaundice
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- No cerebrovascular accident (CVA) within 6 months, no myocardial infarction (MI) within 6 months
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Negative pregnancy test in females of reproductive age
- Anticoagulation is permitted but patients may not be on warfarin
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin =< 1.5 X upper limits of normal
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/ per Cockroft-Gault equation for patients with creatinine levels above institutional normal
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
- Patients who have had previous chemotherapy or radiotherapy for pancreatic adenocarcinoma prior to entering the study
- Pathologic subtypes other than pure adenocarcinoma; acinar cell carcinoma, squamous cell carcinoma, spindle cell carcinoma, neuroendocrine cancer, and mixed types are not eligible
- Patients who are receiving any investigational agents
- Patients with borderline resectable, locally advanced or metastatic disease
- History of allergic reactions attributed to fluorouracil (5-FU), leucovorin, irinotecan or oxaliplatin or to compounds of similar chemical or biologic composition
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active liver disease including viral or non-viral hepatitis and cirrhosis, chronic diarrhea or inflammatory disease of the colon or rectum, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with these agents
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- Currently active second malignancy other than non-melanoma skin cancer or carcinoma in-situ of the cervix; patients are not considered to have a “currently active” malignancy if they have completed therapy and have no evidence of recurrence for at least 5 years
- Pre-existing neuropathy greater than grade 1
- Inflammatory bowel disease that is uncontrolled or on active treatment (Crohn’s disease, ulcerative colitis)
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02782182.
PRIMARY OBJECTIVES:
I. To evaluate the percentage of pancreatic cancer patients able to complete the full 4 months of preoperative chemotherapy and undergo a resection.
SECONDARY OBJECTIVES:
I. To assess the percentage of patients able to complete all therapy, including preoperative chemotherapy, surgery, and postoperative therapy.
II. To assess treatment-related toxicity during preoperative therapy.
III. To assess intra-operative and post-operative complications.
IV. To assess the histopathologic (R0/R1) resection rate after preoperative therapy.
V. To determine disease free survival (DFS) for patients who undergo resection.
VI. To determine progression free survival (PFS) for all patients.
VII. To determine overall survival (OS) from the date of first treatment.
TERTIARY OBJECTIVES:
I. To describe the differences in genetic alteration between patients who experience a pathologic complete or partial response and patients who experience only toxicity after pre-operative leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (mFOLFIRINOX).
II. To assess the correlation between low BNIP3 and high v-myc myelocytomatosis viral oncogene homolog (c-MYC) expression with clinical outcome, PFS, DFS, and OS.
III. To assess the correlation between levels of elevated micro ribonucleic acid (miR)-551a, miR-48, miR-21 exosomes isolated from peripheral/portal blood/tissue with clinical outcome, PFS, DFS, and OS.
IV. To evaluate whether pre-chemotherapy measures of vulnerability including sarcopenia and functional status correlates with higher rates of chemotherapy-related toxicity and poorer clinical outcome (DFS, PFS, OS), especially in older adults.
V. To assess whether the number of pancreatic circulating tumor cells (CTC) both in peripheral and portal blood correlate with poorer clinical outcomes (DFS, PFS, OS).
VI. To develop patient-derived xenografts (PDX) in order to study the patient’s tumor biology and ultimately guide therapy.
VII. To determine if PDX models offer a tool for studying a patient’s tumor biology and guiding treatment upon disease progression.
OUTLINE:
PRE-OPERATIVE CHEMOTHERAPY: Patients receive oxaliplatin intravenously (IV) over 2 hours on days 1 and 15, leucovorin calcium IV over 2 hours on days 1 and 15, irinotecan hydrochloride IV over 90-120 minutes on days 1 and 15, and fluorouracil IV over 46 hours on days 1-2 and 15-16. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity before surgery.
SURGERY: Patients undergo tumor resection surgery 4-6 weeks after completion of pre-operative chemotherapy.
POST-OPERATIVE CHEMOTHERAPY: Within 4-6 weeks after surgery, patients receive chemotherapy as in pre-operative chemotherapy. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity before surgery.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationUniversity of Chicago Comprehensive Cancer Center
Principal InvestigatorHedy Lee Kindler
- Primary IDIRB15-1630
- Secondary IDsNCI-2016-01120
- ClinicalTrials.gov IDNCT02782182