Clinical trial NCT06572813: Bortezomib Combined with PD-1 MAb and MFOLFIRINOX for Metastatic Pancreatic Cancer
Official title: Bortezomib Combined with PD-1 MAb and MFOLFIRINOX for First-line Treatment of Metastatic Pancreatic Cancer：An Exploratory Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pancreas Cancer
Keywords: metastatic pancreatic cancer
bortezomib
PD-1 antibody
chemotherapy
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2024-08-27
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: Up to 2 years.
measure: Phase 2: Objective reponse rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Duration of remission （DoR）
timeFrame: Up to 2 years
measure: Progression-free survival （PFS）
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: First Affiliated Hospital of Zhejiang University Schlool of Medicine
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: Tingbo Liang
role: PRINCIPAL_INVESTIGATOR
References: