Bortezomib Combined with PD-1 MAb and MFOLFIRINOX for Metastatic Pancreatic Cancer
- Conditions
- Pancreas Cancer
- Interventions
- Registration Number
- NCT06572813
- Lead Sponsor
- Zhejiang University
- Brief Summary
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
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 63
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2 (Dose extension) Sintilimab 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. Phase 1 (Drug Tolerance Evaluation) Sintilimab 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. Phase 1 (Drug Tolerance Evaluation) mFOLFIRINOX 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. Phase 1 (Drug Tolerance Evaluation) Bortezomib Injection 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. Phase 2 (Dose extension) Bortezomib Injection 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. Phase 2 (Dose extension) mFOLFIRINOX 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.
- Primary Outcome Measures
Name Time Method Phase 1: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 Up to 2 years. 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.
Phase 2: Objective reponse rate (ORR) Up to 2 years The proportion of patients who had tumor evaluated as PR according to RECIST1.1 criteria during phase 2
- Secondary Outcome Measures
Name Time Method Disease control rate (DCR) Up to 2 years The proportion of patients who had tumor evaluated as PR or SD according to RECIST1.1 criteria during phase 2
Progression-free survival （PFS） Up to 2 years The time from enrolled to disease pregression or death from any cause during phase 2
Duration of remission （DoR） Up to 2 years 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
Overall survival (OS) Up to 2 years The time from enrolled to death from any cause during phase 2
Trial Locations
- Locations (1)
First Affiliated Hospital of Zhejiang University Schlool of Medicine
🇨🇳Hangzhou, Zhejiang, China