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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pancreatic Adenocarcinoma Resectable, Neoadjuvant Chemotherapy

Intervention / Treatment
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* Drug: AG regimen
* Drug: mFolfirinox


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant Chemotherapy<br>Patients receive the sequential neoadjuvant chemotherapy of AG regimen (nab-paclitaxel plus gemcitabine) and mFOLFIRINOX before resection. | Drug: AG regimen<br>* Combination of Nab-paclitaxel 125 mg/m^2 and Gemcitabine 1000 mg/m^2<br>* Other names: Nab-paclitaxel and Gemcitabine;Drug: mFolfirinox<br>* Folic acid 400mg/m^2, 5- fluorouracil 2400mg/m^2 for 46h, irinotecan 135mg/m^2 and oxaliplatin 68mg/m^2<br>* Other names: Folic acid, 5- fluorouracil, irinotecan and oxaliplatin;|
| No Intervention: control<br>Patients receive surgical treatment without any neoadjuvant treatments. | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic Cancer, Pancreatic Adenocarcinoma, Gemcitabine, Nab-paclitaxel, Modified Folfirinox, Sequential treatment