Acinar Cell Adenocarcinoma of the Pancreas, Duct Cell Adenocarcinoma of the Pancreas, Stage IIA Pancreatic Cancer, Stage IIB Pancreatic Cancer, Stage I Pancreatic Cancer
Conditions
Brief summary
This phase II trial studies how well combination chemotherapy before and after surgery works in treating patients with localized pancreatic cancer. 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 or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.
Detailed description
PRIMARY OBJECTIVES: I. To determine the progression-free survival in patients with resectable non-metastatic pancreatic cancer treated with peri-operative modified leucovorin calcium, fluorouracil, irinotecan hydrochloride, oxaliplatin (mFOLFIRINOX). SECONDARY OBJECTIVES: I. Determine overall survival. II. Determine objective response rate after neoadjuvant mFOLFIRINOX. TERTIARY OBJECTIVES: I. Compare R0 resection rate and pathologic stage with institutional historical controls who did not receive neoadjuvant therapy. II. Correlate early metabolic response, determined by changes in glucose metabolism using positron emission tomography (PET) scanning, with pathologic response, R0 resection, and pathologic stage. III. Correlate early metabolic response, determined by changes in glucose metabolism using PET scanning, with progression-free and overall survival. IV. Correlate pre-operative response of CA19-9 with progression-free and overall survival. V. Collect and bank serial serum and plasma specimens from subjects for future correlative biomarker studies. VI. Collect and bank tumor tissue from subjects prior to treatment (from the diagnostic endoscopic ultrasonography \[EUS\]-guided biopsy) and after treatment with six cycles of FOLFIRINOX (from the surgical specimen) for future correlative biomarker studies. OUTLINE: NEOADJUVANT THERAPY: Patients receive mFOLFIRINOX comprising oxaliplatin intravenously (IV) over 2 hours, levoleucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV continuously for 46 hours on day 1. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Beginning 3-8 weeks after completion of neoadjuvant therapy patients undergo surgical resection. ADJUVANT THERARPY: Beginning within 12 weeks after surgery, patients receive mFOLFIRINOX as in neoadjuvant therapy. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 3 years, every 6 months for 2 years, and then annually thereafter.
Interventions
DRUGoxaliplatin
Given IV
DRUGleucovorin calcium
Given IV
DRUGirinotecan hydrochloride
Given IV
DRUGfluorouracil
Given IV
PROCEDUREtherapeutic conventional surgery
Undergo surgical resection
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
Yale University
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologic or cytologic documentation of pancreatic adenocarcinoma * Resectable pancreatic adenocarcinoma disease as defined as follows: * No evidence of extrapancreatic disease by cross sectional imaging, PET scan, or laparoscopy, including nodal involvement beyond the peripancreatic tissues and/or distant metastases; * No evidence of tumor extension to superior mesenteric artery, hepatic artery, celiac axis, aorta, or inferior vena cava, and no evidence of occlusion or encasement of the superior mesenteric vein or superior mesenteric vein/portal vein confluence, as assessed by computed tomography (CT) using pancreatic protocol (or magnetic resonance imaging \[MRI\] in patients who cannot undergo CT) and EUS * No prior treatment (chemotherapy, biological therapy, or radiotherapy) for resectable pancreatic cancer * No prior treatment with oxaliplatin, irinotecan (irinotecan hydrochloride), fluorouracil or capecitabine * Patients who received chemotherapy \> 5 years ago for malignancies other than pancreatic cancer are eligible * There is no evidence of the second malignancy at the time of study entry * \> 4 weeks since major surgery * No other concurrent anticancer therapy * Eastern Cooperative Oncology Group (ECOG) performance status: 0-1 * No other malignancy within past five years except basal cell carcinoma of the skin, cervical carcinoma in situ, or non-metastatic prostate cancer * Paraffin block or slides must be available * Adequate organ function * No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung * No \>= grade 2 sensory peripheral neuropathy * No uncontrolled seizure disorder, active neurological disease, or known central nervous system (CNS) disease * No significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment * No history of chronic diarrhea * Not pregnant and not nursing * No other medical condition or reason that, in the opinion of the investigator, would preclude study participation * Absolute neutrophil count \>= 1,500/uL * Platelet count \>= 100,000/uL * Hemoglobin \>= 9 g/dL * Creatinine \< 1.5 X upper limit of normal (ULN) or * Estimated glomerular filtration rate (GFR) \> 30 ml/min * Bilirubin =\< 1.5 X ULN * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 X ULN * Negative pregnancy test in women of childbearing age
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Rate | At 12 months | Evaluated using a one-sided 0.10-alpha level exact test. Summarized using Kaplan-Meier curves |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 5 years | Summarized using Kaplan-Meier curves. |
| Objective Response Rate | Up to 5 years | The overall response rate (ORR) was assessed as the percentage of participants with a best overall disease response |
| Progression Free Survival Rate | up to 5 years | Evaluated using a one-sided 0.10-alpha level exact test. Summarized using Kaplan-Meier curves |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJill Lacy, MD
Yale University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65 years |
| Baseline Cancer Antigen 19-9 (CA 19-9) concentration | 131 U/mL |
| Eastern Cooperative Oncology Group (ECOG) performance status 0-Fully active, able to carry on all pre-disease performance without restriction | 36 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 1-No physically strenuous activity but ambulatory and can carry out light or sedentary activities | 10 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 2-Capable of selfcare but can't carry out any work activities; up to about 50% of waking hours | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 3-Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 4-Completely disabled; cannot carry on any selfcare; totally confined to bed or chair | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 5-Dead | 0 Participants |
| Genetic Testing BRCA2 germline mutation | 1 Participants |
| Genetic Testing No germline mutation | 21 Participants |
| Genetic Testing Unavailable | 24 Participants |
| Histology Moderately differentiated | 17 Participants |
| Histology Poorly differentiated | 22 Participants |
| Histology Unknown | 7 Participants |
| Histology Well differentiated | 0 Participants |
| Location of primary tumor Endobiliary stent | 30 Participants |
| Location of primary tumor Pancreatic body/tail | 13 Participants |
| Location of primary tumor Pancreatic head | 33 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment United States | 46 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 31 Participants |
| Vascular involvement by tumor No venous involvement | 22 Participants |
| Vascular involvement by tumor SMV or (PV) abutment with contour irregularity | 8 Participants |
| Vascular involvement by tumor Superior mesenteric vein (SMV) or portal vein (PV) abutment without contour irregularity | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 46 |
| other Total, other adverse events | 46 / 46 |
| serious Total, serious adverse events | 13 / 46 |
Outcome results
None listed