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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Anti-PD-1 monoclonal antibody

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 Type: Interventional
• Enrollment (Estimated): 830
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tingbo Liang, MD PhD; Phone Number: 8613666676128; Email: liangtingbo@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • the First Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Liang TingBo, MD, PHD; Phone Number: 086-571-87236688; Email: liangtingbo@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	The time of treatment until documented tumor progreesion.	Through the study peirod, for 3 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 8, 2019
• First Posted (Actual): June 12, 2019

Study Record Updates

• Last Update Posted (Actual): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: combination therapy; PD-1; Pancreatic cancer; FOLFIRINOX
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: CISPD-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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