Sequential Use of AG and mFOLFIRINOX as Neoadjuvant Chemotherapy for Resectable Pancreatic Cancer

Sequential Use of Nab-paclitaxel Plus Gemcitabine and mFOLFIRINOX as Neoadjuvant Chemotherapy for Resectable Pancreatic Cancer: A Randomized Control Study

The prognosis of pancreatic cancer is extremely poor. Current guidelines recommend Nab-paclitaxel, Gemcitabine and modified Folfirinox as the first-line chemotherapeutic regimen. Studies have shown that sequential chemotherapeutic regimen can effectively delay the drug resistance and improve the effect of chemotherapy. Here investigators intend to assess the effect of sequential treatment with Nab-paclitaxel plus Gemcitabine and modified Folfirinox as neoadjuvant chemotherapy for resectable pancreatic adenocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Adenocarcinoma Resectable; Neoadjuvant Chemotherapy
• Intervention / Treatment: Drug: AG regimen; Drug: mFolfirinox

Detailed Description

Investigators chose resectable pancreatic adenocarcinoma patients. The planned treatment was given to the participants after randomization. Tumor size, recurrence-free survival, overall survival, drugs related side effects and other endpoints events were recorded and analyzed, to assess the sequential treatment with Nab-paclitaxel plus Gemcitabine and modified Folfirinox could or couldn't benefit the prognosis of resectable pancreatic adenocarcinoma.

• Study Type: Interventional
• Enrollment (Anticipated): 416
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University
      • Contact: Qi Zhang, MD; Phone Number: 8613819137113; Email: zhangqi86@zju.edu.cn

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:

• Pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma (PDAC).
• No evidence of distant metastasis (such as liver, peritoneum, lung) evaluated by abdominal contrast-enhanced CT, MRI, and chest CT. PET/CT or other imaging examinations would be used if necessary.
• Initial assessment for definitive resectable tumors (resectability judgment is based on CT enhanced scan or magnetic resonance imaging, NCCN2018 first edition standard).
• ECOG score 0 or 1.
• Serum creatinine level is normal, and serum total bilirubin level is less than 1.5 x ULN.
• ALT and AST are less than 2 x ULN.
• If biliary obstruction is observed, biliary decompression should be performed when the patient is randomly assigned to receive neoadjuvant chemotherapy.
• Leukocyte count (> 3.5 x 10^6 /mL), neutrophil count (> 1.5 x 10^6 /mL), platelet count (> 80 x 10^6 /mL), hemoglobin (> 9 g/dL).
• Signed informed consent.

Exclusion Criteria:

• History of malignance treatment in the past, excluding basal and cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma
• Tumor is a local recurrent lesion.
• Imaging confirmed severe portal hypertension / cavernous transformation.
• Ascites
• Gastric outlet obstruction
• Respiratory failure requires supplementation of oxygen.
• Immune deficiency syndrome, such as active tuberculosis and HIV infection.
• Hematological precancerous diseases, such as myelodysplastic syndromes.
• Major cardiovascular diseases (including myocardial infarction, unstable angina, congestive heart failure, severe uncontrolled arrhythmia) during the past six months of enrollment.
• Evidence of clinical-related or previous interstitial lung disease, such as noninfectious pneumonia or pulmonary fibrosis, or baseline chest CT scan or chest X-ray findings
• Previous or physical findings of central nervous system disease, except for adequately treated (e.g. primary brain tumors, uncontrolled seizures or strokes with standard medications)
• Preexisting neuropathy > 1 (NCI CTCAE).
• Allograft requires immunosuppressive therapy or other major immunosuppressive therapies.
• Severe serious wounds, ulcers or fractures.
• Confirmed coagulant disease.
• Clinical evaluation is unacceptable.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Neoadjuvant Chemotherapy; Patients receive the sequential neoadjuvant chemotherapy of AG regimen (nab-paclitaxel plus gemcitabine) and mFOLFIRINOX before resection.	Drug: AG regimen; Combination of Nab-paclitaxel 125 mg/m^2 and Gemcitabine 1000 mg/m^2; Other Names: Nab-paclitaxel and Gemcitabine; Drug: mFolfirinox; Folic acid 400mg/m^2, 5- fluorouracil 2400mg/m^2 for 46h, irinotecan 135mg/m^2 and oxaliplatin 68mg/m^2; Other Names: Folic acid, 5- fluorouracil, irinotecan and oxaliplatin
NO_INTERVENTION: control; Patients receive surgical treatment without any neoadjuvant treatments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	The time of initial response until documented tumor recurrence.	Up to approximately 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The time of initial response until documented patient death	Up to approximately 60 months
Objective response rate	The proportion of patients with tumor size reduction of a predefined amount and for a minimum time period	Up to approximately 60 months
Carbohydrate antigen 19-9	Serum Carbohydrate antigen 19-9 level	Up to approximately 60 months
EORTC QLQ - PAN26 score	QLQ score assessed by the European Organization for Research and Treatment of Cancer Quality of Life scale for pancreatic cancer (EORTC QLQ - PAN26. For details: PMID 10533475.)	Up to approximately 60 months
Serious adverse events incidence	The proportion of patients with grade 3/4 adverse events	Up to approximately 60 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Tingbo Liang, MD PhD, Department of HBP Surgery, SAHZJU

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 20, 2018
• Primary Completion (ANTICIPATED): October 20, 2023
• Study Completion (ANTICIPATED): October 20, 2024

Study Registration Dates

• First Submitted: November 17, 2018
• First Submitted That Met QC Criteria: November 20, 2018
• First Posted (ACTUAL): November 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 23, 2018
• Last Update Submitted That Met QC Criteria: November 20, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Gemcitabine; Pancreatic Cancer; Nab-paclitaxel; Pancreatic Adenocarcinoma; Sequential treatment; Modified Folfirinox
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Vitamin B Complex; Hematinics; Gemcitabine; Paclitaxel; Fluorouracil; Oxaliplatin; Irinotecan; Folic Acid
• Other Study ID Numbers: CISPD-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No