Clinical trial NCT03983057: Combination of Anti-PD-1 Antibody and Chemotherapy in Pancreatic Cancer
Official title: Study on Therapeutic Effect of Combination of Anti-PD-1 Antibody and Chemotherapy in Locally Advanced or Borderline Resectable Pancreatic Cancer Patients: A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: Pancreatic cancer
PD-1
FOLFIRINOX
combination therapy
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2019-06-12
Enrollment: 830
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
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 FOLFIRINOX or modified-FOLFIRINOX as the first-line chemotherapeutic regimen. Studies have shown that immunotherapy with Anti-PD-1 antibody can effectively increase the response rate and prolong patient survival in a number of cancer diseases. Here investigators intend to compare the therapeutic effects of modified-FOLFIRINOX alone and the combination of modified-FOLFIRINOX and Anti-PD-1 antibody in patients with borderline resectable and locally advanced pancreatic cancer.

Detailed description: Investigators chose borderline resectable and locally advanced pancreatic cancer patients. The planned treatment was given to the participants after randomization. Response rate, recurrence-free survival, overall survival, drugs related side effects and other endpoints events were recorded and analyzed, to assess the combination treatment with modified-FOLFIRINOX and Anti-PD-1 antibody could or couldn't benefit the patients with borderline resectable and locally advanced pancreatic cancer.

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 borderline resectable or locally advanced tumors (resectability judgment is based on CT enhanced scan or magnetic resonance imaging, NCCN2019 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
* History of participation of other clinical trails within 4 weeks
* History of immunotherapy within 4 weeks
* History of receiving chemotherapy, radiotherapy and molecular target therapy within 2 weeks
* 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: Progression-free survival
timeFrame: Through the study peirod, for 3 years
Secondary outcomes:
measure: Resection rate
timeFrame: Through the study peirod, for 3 years
measure: R0 rate
timeFrame: Through the study peirod, for 3 years
measure: Objective response rate
timeFrame: Through the study peirod, for 3 years
measure: Disease control rate
timeFrame: Through the study peirod, for 3 years
measure: Overall survival
timeFrame: Through the study peirod, for 3 years
measure: EORTC QLQ - PAN26 score
timeFrame: Through the study peirod, for 3 years
measure: Adverse effects
timeFrame: Through the study peirod, for 3 years
measure: Carbohydrate antigen 19-9
timeFrame: Through the study peirod, for 3 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: the First Affiliated Hospital, School of Medicine, Zhejiang University
state: Zhejiang
Study officials:
References: