Clinical trial NCT03750669: Sequential Use of AG and mFOLFIRINOX as Neoadjuvant Chemotherapy for Resectable Pancreatic Cancer
Official title: Sequential Use of Nab-paclitaxel Plus Gemcitabine and mFOLFIRINOX as Neoadjuvant Chemotherapy for Resectable Pancreatic Cancer: A Randomized Control Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Adenocarcinoma Resectable
Neoadjuvant Chemotherapy
Keywords: Pancreatic Cancer
Pancreatic Adenocarcinoma
Gemcitabine
Nab-paclitaxel
Modified Folfirinox
Sequential treatment
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2018-11-23
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: Investigators chose resectable pancreatic adenocarcinoma patients. The planned treatment was given to the participants after randomization. Tumor size, event-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.

Eligibility criteria: 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.

Primary outcomes:
measure: event-free survival (EFS)
timeFrame: From randomization to any of the following events: progression of disease that precludes resection, local or distant recurrence, or death due to any cause, whichever occurs first. Up to approximately 60 months.
Secondary outcomes:
measure: Overall survival
timeFrame: From randomization to death due to any cause. Up to approximately 60 months.
measure: Objective response rate
timeFrame: From randomization to the end of neoadjuvant therapy. Up to approximately 60 months.
measure: Carbohydrate antigen 19-9
timeFrame: Up to approximately 60 months
measure: Serious adverse events incidence
timeFrame: Up to approximately 60 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The second affiliated hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: Department of HBP Surgery, SAHZJU
name: Tingbo Liang, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: