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

Comparison of Therapeutic Effect Between Combination of Anti-PD-1 Antibody With mFOLFIRINOX and mFOLFIRINOX Alone in Metastatic Pancreatic Cancer Patients: A Randomized Clinical Trial

The prognosis of pancreatic cancer is extremely poor. NCCN 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 metastatic pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Chemotherapy; Drug: Combination drug

Detailed Description

Metastatic pancreatic cancer patients will be enrolled in this trial. Investigators will assign patients to the treatment after randomization. The primary endpoint is overall survival. Response rate, progression-free survival, drugs related side effects and other endpoints events will be recorded and analyzed, to assess the combination treatment with modified-FOLFIRINOX and Anti-PD-1 antibody could or couldn't benefit the patients with metastatic pancreatic cancer.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • the First Affiliated Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• •Pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma (PDAC).

  • Recurrent disease or metastatic disease (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.
  • Never receive any systematic treatment or Progression after fisrt line Gemcitabine base chemotherapy
  • 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.
  • Signed informed consent.

Exclusion Criteria:

• •History of participation of other clinical trails within 4 weeks

  • History of autoimmune disease or other condition receiving glucocorticoid treatment
  • History of receiving chemotherapy within 2 weeks
  • History of radiotherapy and molecular target therapy within 2 weeks
  • History if active tuberculosis
  • History of malignance treatment in the past, excluding basal and cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma
  • Major cardiovascular diseases (including myocardial infarction, unstable angina, congestive heart failure, severe uncontrolled arrhythmia) during the past six months of enrollment.
  • Hematological precancerous diseases, such as myelodysplastic syndromes.
  • 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).
  • Immune deficiency syndrome, such as active tuberculosis and HIV infection.
  • Allograft requires immunosuppressive therapy or other major immunosuppressive therapies.
  • Severe serious wounds, ulcers or fractures.
  • 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
Active Comparator: 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	Drug: Chemotherapy; modified-FOLFIRINOX
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 200mg.	Drug: Combination drug; 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
Overall survival	The period from the first study treatment to any cause of death	Through the study peirod, for 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resection rate	The number of cases received surgery / the total number of evaluable cases (%)	Through the study peirod, for 3 years
Objective response rate	The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%)	Through the study peirod, for 3 years
Disease control rate	The number of cases in which response (PR + CR) and stable disease (SD) are achieved from the start of cell infusion/the total number of evaluable cases (%)	Through the study peirod, for 3 years
Progression-free survival	The period from the first treatment to the first evaluation of PD or any cause of death	Through the study peirod, for 3 years
Adverse effects	Adverse events occurring through the study treatment, such as abnormalities or changes in laboratory examinations, physical examinations, vital signs, etc.	Through the study peirod, for 3 years
Carbohydrate antigen 19-9	The change of CA 199	Through the study peirod, for 3 years
EORTC QLQ - PAN26 score	The change of the quality of life	Through the study peirod, for 3 years

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2019
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 6, 2019

Study Record Updates

• Last Update Posted (Actual): January 27, 2023
• Last Update Submitted That Met QC Criteria: January 25, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Anti-PD-1 Antibody
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: CISPD3

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