Neoadjuvant Modified FOLFIRINOX in Borderline Resectable Pancreatic Cancer

Sponsor

Asan Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT02749136

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the feasibility and efficacy outcomes of neoadjuvant modified FOLFIRINOX and postoperative gemcitabine in patients with borderline resectable pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Adenocarcinoma	Drug: Preoperative modified FOLFIRINOX and postoperative gemcitabine	Phase 2

Detailed Description

Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. The 5-year survival rate in overall patients is less than 6% due to late clinical manifestation and the systemic nature of the disease at presentation. Even in patients with resectable disease, estimated 5-year survival rates after resection are between 15% and 20%. Traditionally, resection alone is regarded as inadequate for cure. Therefore, systemic and/or combined chemotherapy and radiotherapy have been used as preoperative or postoperative therapy.

Neoadjuvant treatment offers several theoretical advantages over an initial resection. Early delivery of systemic therapy for all patients which might lead to the higher rates of negative margin resection rate, and enhanced patient selection for surgery. Although neoadjuvant treatment has been established as a standard of care for resectable or locally advanced disease of breast, gastric, and rectal cancers, the role of neoadjuvant treatment in patients with pancreatic cancer is not clear at present.

There is no global consensus on the management of patients with borderline resectable pancreatic cancer. If initially resected, postoperative adjuvant chemotherapy or chemoradiotherapy is standard. However, there is no standard regimen for neoadjuvant chemotherapy for pancreatic cancer. Recent pivotal phase 2/3 trial has demonstrated that FOLFIRINOX improved the response rates and survival outcomes of patients with metastatic pancreatic cancer compared to gemcitabine.

Because of higher response rates (about 30%) with FOLFIRINOX, this regimen is now widely investigated in the neoadjuvant setting. Therefore, investigators hypothesize that neoadjuvant FOLFIRINOX may enhance the outcomes of patients with borderline resectable pancreatic cancer. This study will assess the feasibility and efficacy outcomes of neoadjuvant modified FOLFIRINOX and postoperative gemcitabine in patients with borderline resectable pancreatic cancer.

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 2 Study of Neoadjuvant Modified FOLFIRINOX in Patients With Borderline Resectable Pancreas Adenocarcinoma

Study Start Date :

May 1, 2016

Actual Primary Completion Date :

Sep 1, 2019

Actual Study Completion Date :

Nov 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Perioperative chemotherapy Preoperative mFOLFIRINOX, every 2 weeks, 8 cycles Postoperative gemcitabine, every 4 weeks, 3-6 cycles	Drug: Preoperative modified FOLFIRINOX and postoperative gemcitabine Preoperative mFOLFIRINOX, every 2 weeks, 8 cycles Oxaliplatin IV 85 mg/m2 Day (D) 1 Irinotecan IV 180 mg/m2 D1 5-FU continuous IV infusion 2,400 mg/m2 over 46 hours D1-2 Leucovorin IV 400 mg/m2 D1 Postoperative gemcitabine, every 4 weeks, 3-6 cycles - Gemcitabine 1,000 mg/ m2 D1, 8, and 15

Arm

Intervention/Treatment

Experimental: Perioperative chemotherapy

Preoperative mFOLFIRINOX, every 2 weeks, 8 cycles Postoperative gemcitabine, every 4 weeks, 3-6 cycles

Drug: Preoperative modified FOLFIRINOX and postoperative gemcitabine

Preoperative mFOLFIRINOX, every 2 weeks, 8 cycles Oxaliplatin IV 85 mg/m2 Day (D) 1 Irinotecan IV 180 mg/m2 D1 5-FU continuous IV infusion 2,400 mg/m2 over 46 hours D1-2 Leucovorin IV 400 mg/m2 D1 Postoperative gemcitabine, every 4 weeks, 3-6 cycles - Gemcitabine 1,000 mg/ m2 D1, 8, and 15

Outcome Measures

Primary Outcome Measures

1-year progression-free survival (PFS) rate [1 year]
PFS rate at 1 year

Secondary Outcome Measures

Progression-free survival (PFS) [3 years]
Median PFS
Overall survival (OS) [3 years]
Median OS
Macroscopic complete resection rate [5 months]
The rate of no gross residual disease after surgery
Response rate [4 months]
Response rate defined by Response Evaluation Criteria in Solid Tumor version 1.1
Toxicity profile [1 year]
Adverse events graded by National Cancer Institute Common Terminology Criteria version 4.03
Biomarker analysis [3 years]
Blood-based biomarker analysis for the correlation with response rate, progression-free survival and overall survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients aged 19 years and older
Cytologically or histologically confirmed adenocarcinoma of the pancreas
Met the NCCN criteria for borderline resectable disease (assessed at Aug 23rd, 2015)
No previous chemotherapy or radiotherapy
Eastern Cooperative Oncology Group (ECOG) performance status 0 ~ 1
Adequate bone marrow function as defined by platelets ≥ 100 x 109/L and neutrophils ≥ 1.5 x 109/L
Adequate renal function, with serum creatinine < 1.5 x upper limit of normal (ULN)
Adequate hepatic function with serum total bilirubin < 2 mg/dL, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN
No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other non life-threatening cancer (i.e., prostate or thyroid cancer) except where treated with curative intent > 5 years previously without evidence of relapse
Written informed consent to the study

Exclusion Criteria:

No potentially resectable disease or no metastatic disease
Locally advanced unresectable disease according to the NCCN criteria
Histologically confirmed adenosquamous carcinoma
Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance
Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy
Obstruction of gastrointestinal tract
Active gastrointestinal bleeding
Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol
Female subjects who are pregnant or lactating, or males and females of reproductive potential not willing or not able to employ a highly effective method of birth control/contraception to prevent pregnancy from 2 weeks before receiving study drug until 3 months after receiving the last dose of study drug. A highly effective method of contraception is defined as having a low failure rate (< 1% per year) when used consistently and correctly.