Preoperative Folfirinox for Resectable Pancreatic Adenocarcinoma - A Phase II Study

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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Adenocarcinoma; Resectable Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Poorly Differentiated Malignant Neoplasm; Undifferentiated Pancreatic Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin Calcium; Drug: Irinotecan Hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Fluorouracil; Given IV; Drug: Oxaliplatin; Given IV; Drug: Leucovorin Calcium; Given IV; Other Names: CF; Drug: Irinotecan Hydrochloride; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Time from enrollment to the earlier of death or disease progression. Will be estimated with Kaplan Meier curves.	Up to 2 years
Overall Survival	Time from enrollment to death from any cause. Will be estimated with Kaplan Meier curves.	Up to 2 years
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.	Up to 30 days after end of treatment or to the day prior to surgery
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.	Up to 2 years
Number of Participants Achieving Major Pathologic Response	Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.	Up to 2 years
Number of Participants Achieving R0 Resection	Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.	Up to 2 years
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.	Up to 30 days

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Davendra Sohal, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: January 20, 2015
• First Submitted That Met QC Criteria: January 20, 2015
• First Posted (Estimate): January 26, 2015

Study Record Updates

• Last Update Posted (Actual): July 13, 2018
• Last Update Submitted That Met QC Criteria: June 13, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms; Adenocarcinoma; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Calcium; Levoleucovorin
• Other Study ID Numbers: CASE4214 (Other Identifier: Case Comprehensive Cancer Center); P30CA043703 (U.S. NIH Grant/Contract); NCI-2014-02277 (Registry Identifier: CTRP (Clinical Trial Reporting Program))