Bortezomib Combined with PD-1 MAb and MFOLFIRINOX for First-line Treatment of Metastatic Pancreatic Cancer：An Exploratory Clinical Trial
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 63
- Locations
- 1
- Primary Endpoint
- Phase 1: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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
- •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
Arms & Interventions
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.
Intervention: mFOLFIRINOX (Drug)
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.
Intervention: Bortezomib Injection (Drug)
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.
Intervention: Sintilimab (Drug)
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.
Intervention: Bortezomib Injection (Drug)
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.
Intervention: Sintilimab (Drug)
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.
Intervention: mFOLFIRINOX (Drug)
Outcomes
Primary Outcomes
Phase 1: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: 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)
Time Frame: Up to 2 years
The proportion of patients who had tumor evaluated as PR according to RECIST1.1 criteria during phase 2
Secondary Outcomes
- Disease control rate (DCR)(Up to 2 years)
- Progression-free survival （PFS）(Up to 2 years)
- Duration of remission （DoR）(Up to 2 years)
- Overall survival (OS)(Up to 2 years)
Investigators
TingBo Liang
Professor
Zhejiang University