Pancreatic Adenocarcinoma, Poorly Differentiated Malignant Neoplasm, Resectable Pancreatic Cancer, Stage IA Pancreatic Cancer, Stage IB Pancreatic Cancer, Stage IIA Pancreatic Cancer, Stage IIB Pancreatic Cancer, Stage III Pancreatic Cancer, Undifferentiated Pancreatic Carcinoma
Conditions
Brief summary
This phase II trial studies how well combination chemotherapy works in treating patients with pancreatic cancer before undergoing surgery. Drugs used in chemotherapy, such as irinotecan hydrochloride, oxaliplatin, leucovorin calcium, and fluorouracil (FOLFIRINOX), 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. Giving more than one drug (combination chemotherapy) before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Detailed description
PRIMARY OBJECTIVES: I. To determine feasibility of preoperative FOLFIRINOX for resectable pancreatic adenocarcinoma. SECONDARY OBJECTIVES: I. To determine safety and toxicity of preoperative FOLFIRINOX. II. To determine response rate. III. To determine proportion achieving major pathologic response - per College of American Pathologists (CAP) criteria. IV. To determine proportion achieving R0 resection. V. To determine perioperative (30-day) mortality. VI. To determine the role of cancer antigen (CA)19.9 as potential prognostic and/or predictive biomarker. VII. To determine progression-free survival. VIII. To determine overall survival. OUTLINE: Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride intravenously (IV) over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.
Interventions
DRUGIrinotecan Hydrochloride
Given IV
DRUGOxaliplatin
Given IV
DRUGLeucovorin Calcium
Given IV
DRUGFluorouracil
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically or cytologically confirmed carcinoma of the pancreas; most cases will be adenocarcinoma; cases with undifferentiated or poorly differentiated carcinoma will also be eligible * There should be no evidence of metastatic disease on imaging of the chest, abdomen, and pelvis; this imaging should be either a contrast-enhanced computed tomography (CT) scan, or a contrast-enhanced magnetic resonance imaging (MRI) scan; positron emission tomography (PET) scans alone will not be adequate alternatives; there should be no evidence of occult metastatic disease in the abdomen, confirmed by laparoscopic examination * The primary tumor must be resectable, defined as no involvement (abutment or encasement) of the major arteries (celiac, common hepatic, superior mesenteric) and interface between tumor and vessel (portal, superior mesenteric veins) wall to be less than 180 degrees of the circumference of the vessel wall; this should be confirmed by imaging of the abdomen, either by a contrast-enhanced computed tomography (CT) scan, or a contrast-enhanced magnetic resonance imaging (MRI) scan; PET scans will not be adequate alternatives; for each patient, the resectability must be reviewed by one of the study surgeons * Patient must not have received any cancer-directed therapy (e.g., surgery, chemotherapy, radiation therapy, biologic therapy) for the index diagnosis * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Hemoglobin \>= 10.0 g/dl * Absolute neutrophil count \>= 1,500/mm\^3 * Platelet count \>= 100,000/mm\^3 * Total bilirubin =\< 1.5 X institutional upper limit of normal * Serum creatinine within normal institutional limits, or creatinine clearance (calculated by Cockcroft-Gault) \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal * Women of child-bearing potential and men must agree to use adequate contraception (double-barrier method of birth control or abstinence) for the duration of study participation and for 6 months after completing chemotherapy; should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately * Subjects must have the ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant or breastfeeding women * Pre-existing peripheral neuropathy (grade I or higher)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Undergoing Surgical Resection After Receiving at Least 4 of the 6 Courses of Preoperative Chemotherapy | Up to 12 weeks | Proportion will be estimated using a binomial test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 2 years | Time from enrollment to death from any cause. Will be estimated with Kaplan Meier curves. |
| Incidence of Toxicities Greater Than Grade 2, Using the Common Terminology Criteria for Adverse Events Version 4.0 | Up to 30 days after end of treatment or to the day prior to surgery | Toxicity evaluation will be enumeration of all major toxicities, with proportions calculated for each. |
| Response Rate Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 | Up to 2 years | Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes. |
| Progression-free Survival | Up to 2 years | Time from enrollment to the earlier of death or disease progression. Will be estimated with Kaplan Meier curves. |
| Number of Participants Achieving R0 Resection | Up to 2 years | Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes. |
| Number of Participants Experiencing Perioperative (30-day) Mortality | Up to 30 days | Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes. |
| Number of Participants Achieving Major Pathologic Response | Up to 2 years | Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (FOLFIRINOX) Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Irinotecan Hydrochloride: Given IV
Oxaliplatin: Given IV
Leucovorin Calcium: Given IV
Fluorouracil: Given IV
Laboratory Biomarker Analysis: Correlative studies | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Treatment (FOLFIRINOX) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Number of Patients Undergoing Surgical Resection After Receiving at Least 4 of the 6 Courses of Preoperative Chemotherapy
Proportion will be estimated using a binomial test.
Time frame: Up to 12 weeks
Population: Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.
Secondary
Incidence of Toxicities Greater Than Grade 2, Using the Common Terminology Criteria for Adverse Events Version 4.0
Toxicity evaluation will be enumeration of all major toxicities, with proportions calculated for each.
Time frame: Up to 30 days after end of treatment or to the day prior to surgery
Population: Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.
Secondary
Number of Participants Achieving Major Pathologic Response
Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.
Time frame: Up to 2 years
Population: Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.
Secondary
Number of Participants Achieving R0 Resection
Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.
Time frame: Up to 2 years
Population: Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.
Secondary
Number of Participants Experiencing Perioperative (30-day) Mortality
Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.
Time frame: Up to 30 days
Population: Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.
Secondary
Overall Survival
Time from enrollment to death from any cause. Will be estimated with Kaplan Meier curves.
Time frame: Up to 2 years
Population: Only 1 patient was enrolled on study. Outcome data was not analyzed.
Secondary
Progression-free Survival
Time from enrollment to the earlier of death or disease progression. Will be estimated with Kaplan Meier curves.
Time frame: Up to 2 years
Population: Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.
Secondary
Response Rate Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1
Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.
Time frame: Up to 2 years
Population: Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.