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

Zhejiang University

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Pancreas Cancer

Treatments: Drug: mFOLFIRINOX; Drug: Bortezomib Injection; Drug: Sintilimab

Study type: Interventional

Funder types: Other

Identifiers

NCT06572813

CISPD-7

Details and patient eligibility

About

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

Full 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.

Enrollment: 63 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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63 participants in 2 patient groups

Phase 1 (Drug Tolerance Evaluation)

Experimental group

Description:

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.

Treatment:

Drug: Sintilimab

Drug: Bortezomib Injection

Drug: mFOLFIRINOX

Phase 2 (Dose extension)

Experimental group

Description:

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.

Treatment:

Drug: Sintilimab

Drug: Bortezomib Injection

Drug: mFOLFIRINOX