Pancreas Cancer
Conditions
Keywords
metastatic pancreatic cancer, bortezomib, PD-1 antibody, chemotherapy
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.
Interventions
Bortezomib Injection, a kind of chemotherapy drug
DRUGSintilimab
PD-1 antibody
DRUGmFOLFIRINOX
Combination of oxaliplatin, fluorouracil, irinotecan, leucovorin calcium
Sponsors
Zhejiang University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model 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 subjects with advanced metastatic pancreatic cancer; Secondary Objective: 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Progression-free survival （PFS） | Up to 2 years | The time from enrolled to disease pregression 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 |
Countries
China
Contacts
Primary ContactTingbo Liang
Backup ContactYiwen Chen
Outcome results
None listed