Bortezomib Combined with PD-1 MAb and MFOLFIRINOX for Metastatic Pancreatic Cancer (CISPD-7)

Bortezomib Combined with PD-1 MAb and MFOLFIRINOX for First-line Treatment of Metastatic Pancreatic Cancer：An Exploratory Clinical Trial

This is an single-center, prospective, open-label clinical trial, to explore the safty and efficacy of combination of Bortezomib, Sindilizumab, and mFOLFIRINOX Chemotherapy (oxaliplatin, fluorouracil, irinotecan, leucovorin) in metastatic pancreatic cancer

Study Overview

• Status: Recruiting
• Conditions: Pancreas Cancer
• Intervention / Treatment: Drug: Bortezomib Injection; Drug: Sintilimab; Drug: mFOLFIRINOX

Detailed Description

Phase 1 (Evaluation of Drug Tolerance) Primary objective: To evaluate the tolerability of bortezomib, PD-1 mAb and mFOLFIRINOX in patients with advanced metastatic pancreatic cancer, and to determine the dose of bortezomib in the combination regimen; Secondary objectives: To evaluate the immunogenicity characteristics and safety of the combination regimen of bortezomib, PD-1 mAb and mFOLFIRINOX in patients with advanced metastatic pancreatic cancer; Phase 2 (Dose Expansion) Primary objective: To evaluate the tolerability and efficacy of the combination regimen of bortezomib, PD-1 mAb and mFOLFIRINOX in patients with advanced metastatic pancreatic cancer; Secondary Objective: ORR; PFS; OS; and to evaluate the immunogenicity and safety of bortezomib, PD-1 mAb and mFOLFIRINOX in subjects with advanced metastatic pancreatic cancer; and to explore biomarkers related to combination therapy.

• Study Type: Interventional
• Enrollment (Estimated): 63
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tingbo Liang; Phone Number: +8619941463683; Email: liangtingbo@zju.edu.cn
• Study Contact Backup: Name: Yiwen Chen; Phone Number: +8615088682641; Email: yiwenchen0705@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • First Affiliated Hospital of Zhejiang University Schlool of Medicine
      • Contact: Yiwen Chen, MD; Phone Number: 86+15088682641; Email: cherry0705@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

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: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 (Drug Tolerance Evaluation); Using a 3 + 3 trial design, bortezomib dose exploration was performed to determine the stage 2 bortezomib dose. The number of participants at this stage is 6-9.	Drug: Bortezomib Injection; Bortezomib Injection, a kind of chemotherapy drug; Drug: Sintilimab; PD-1 antibody; Drug: mFOLFIRINOX; Combination of oxaliplatin, fluorouracil, irinotecan, leucovorin calcium
Experimental: Phase 2 (Dose extension); Phase 2: This phase will adopt competitive enrollment, and the Bayesian prediction probability method will be used to monitor the main efficacy index of the trial ORR in real time to determine the early termination or continue the trial. A maximum number of 57 patients were enrolled in this stage.	Drug: Bortezomib Injection; Bortezomib Injection, a kind of chemotherapy drug; Drug: Sintilimab; PD-1 antibody; Drug: mFOLFIRINOX; Combination of oxaliplatin, fluorouracil, irinotecan, leucovorin calcium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0，including Complete Blood Count, liver function, renal function lab test and other blood test will be evaluated by using CTCAE 5.0 during study.	Up to 2 years.
Phase 2: Objective reponse rate (ORR)	The proportion of patients who had tumor evaluated as PR according to RECIST1.1 criteria during phase 2	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	The proportion of patients who had tumor evaluated as PR or SD according to RECIST1.1 criteria during phase 2	Up to 2 years
Duration of remission （DoR）	The time from the first assessment of the tumor as CR or PR to the first assessment of PD or death from any cause during phase 2	Up to 2 years
Progression-free survival （PFS）	The time from enrolled to disease pregression or death from any cause during phase 2	Up to 2 years
Overall survival (OS)	The time from enrolled to death from any cause during phase 2	Up to 2 years

Collaborators and Investigators

• Sponsor: Zhejiang University
• Investigators: Principal Investigator: Tingbo Liang, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 8, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: chemotherapy; metastatic pancreatic cancer; bortezomib; PD-1 antibody
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: CISPD-7

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
• product manufactured in and exported from the U.S.: No