Combination of Anti-PD-1 Antibody and Chemotherapy in Pancreatic Cancer

Sponsor

Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03983057

Collaborator

(none)

830

Enrollment

Location

Arms

Anticipated Duration (Months)

13.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Drug: Anti-PD-1 monoclonal antibody	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

830 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 1, 2019

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Chemotherapy group Treatment with modified-FOLFIRINOX Folic acid 400mg/m^2, 5- fluorouracil 2400mg/m^2 for 46h, irinotecan 135mg/m^2 and oxaliplatin 68mg/m^2
Experimental: Combination group Treatment with modified-FOLFIRINOX and Anti-PD-1 antibody Folic acid 400mg/m^2, 5- fluorouracil 2400mg/m^2 for 46h, irinotecan 135mg/m^2 and oxaliplatin 68mg/m^2, Anti-PD-1 antibody 3mg/kg	Drug: Anti-PD-1 monoclonal antibody Accompanying with modified-FOLFIRINOX, Anti-PD-1 antibody was applied biweekly.

Arm

Intervention/Treatment

No Intervention: Chemotherapy group

Treatment with modified-FOLFIRINOX Folic acid 400mg/m^2, 5- fluorouracil 2400mg/m^2 for 46h, irinotecan 135mg/m^2 and oxaliplatin 68mg/m^2

Experimental: Combination group

Treatment with modified-FOLFIRINOX and Anti-PD-1 antibody Folic acid 400mg/m^2, 5- fluorouracil 2400mg/m^2 for 46h, irinotecan 135mg/m^2 and oxaliplatin 68mg/m^2, Anti-PD-1 antibody 3mg/kg

Drug: Anti-PD-1 monoclonal antibody

Accompanying with modified-FOLFIRINOX, Anti-PD-1 antibody was applied biweekly.

Outcome Measures

Primary Outcome Measures

Progression-free survival [Through the study peirod, for 3 years]
The time of treatment until documented tumor progreesion.

Secondary Outcome Measures

Resection rate [Through the study peirod, for 3 years]
The proportion of patients with surgeical treatment after treatment
R0 rate [Through the study peirod, for 3 years]
The proportion of patients with completely tumor resection after treatment
Objective response rate [Through the study peirod, for 3 years]
The proportion of patients with tumor size reduction of a predefined amount and for a minimum time period
Disease control rate [Through the study peirod, for 3 years]
The proportion of patients with tumor size reduction or stable
Overall survival [Through the study peirod, for 3 years]
The time of treatment until death.
EORTC QLQ - PAN26 score [Through the study peirod, for 3 years]
QLQ score assessed by the European Organization for Research and Treatment of Cancer Quality of Life scale for pancreatic cancer
Adverse effects [Through the study peirod, for 3 years]
The most common hematologic and non-hemotologic adverse events
Carbohydrate antigen 19-9 [Through the study peirod, for 3 years]
Carbohydrate antigen 19-9 level

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.