Preoperative Folfirinox for Resectable Pancreatic Adenocarcinoma - A Phase II Study

Phase 2

Terminated

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

• Registration Number: NCT02345460
• Lead Sponsor: Case Comprehensive Cancer Center

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.

Study Timeline

• Study First Submitted: 2015-01-20
• Study First Submitted QC: 2015-01-20
• Study First Posted: 2015-01-26
• Study Start: 2015-09
• Primary Completion: 2016-02
• Study Completion: 2016-03
• Status Verified: 2018-06
• Results First Submitted: 2018-06-13
• Results First Submitted QC: 2018-06-13
• Last Update Submitted: 2018-06-13
• Results First Posted: 2018-07-13
• Last Update Posted: 2018-07-13

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (FOLFIRINOX)	Leucovorin Calcium	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.
Treatment (FOLFIRINOX)	Laboratory Biomarker Analysis	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.
Treatment (FOLFIRINOX)	Irinotecan Hydrochloride	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.
Treatment (FOLFIRINOX)	Oxaliplatin	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.
Treatment (FOLFIRINOX)	Fluorouracil	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.

Trial Locations

Locations (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States