Pancreatic Cancer
Conditions
Keywords
borderline resectable, NALIRIFOX, stereotactic body radiation therapy
Brief summary
This multicentric open-label trial will compare the efficacy and safety of stereotactic body radiation therapy (SBRT) followed by NALIRIFOX (5-fluorouracil, leucovorin, irinotecan liposome injection and oxaliplatin) vs NALIRIFOX for borderline resectable pancreatic cancer (BRPC).
Detailed description
Neoadjuvant chemotherapy or chemoradiotherapy can increase the R0 resection rate and improve survival in BRPC. However, there is no standard treatment regimen. The National Comprehensive Cancer Network (NCCN) guidelines recommend FOLFIRINOX (irinotecan + oxaliplatin +5-FU/LV) and FOLFIRINOX+ chemoradiotherapy for PDAC neoadjuvant treatment. Liposomal irinotecan is a new pharmaceutical form of traditional irinotecan. It adopts a special loading technology to encapsulate traditional irinotecan in liposomes, which can avoid its hydrolysis under physiological conditions, increase the affinity with cancer cells, overcome drug resistance, increase the drug uptake by cancer cells, reduce the drug dose,improve the efficacy and reduce the toxic side effects. The aim of this study is to compare the efficacy and safety of NALIRIFOX + surgery + NALIRIFOX or surgery + NALIRIFOX in high-risk patients with resectable pancreatic cancer.
Interventions
50 mg/m² on Day 1 of a 14-day cycle
DRUGOxaliplatin
60 mg/m² on Day 1 of a 14-day cycle
DRUG5-Fluorouracil
2400 mg/m² continuous IV infusion in 46 h
DRUGLeucovorin
400 mg/m² on Day 1 of a 14-day cycle
RADIATIONSBRT
30Gy/5Fx
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age: ≥18 years old. * Histologically or cytologically proven pancreatic ductal adenocarcinoma. * Multidisciplinary assessment as borderline resectable disease. * At least one measurable lesion (according to RECIST v1.1). * No prior antitumor therapy for pancreatic cancer. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 \ 1. * The expected survival time ≥3 months. * Adequate bone marrow function as evidenced by: 1) Absolute neutrophil count (ANC) ≥1.5×10\^9/L, 2) Platelet count ≥100×10\^9/L, 3) Hemoglobin (Hb) ≥90 g/L, 4) White blood cell (WBC) ≥3.0×10\^9/L. * Adequate hepatic function as evidenced by: 1) Serum total bilirubin ≤1.5 × upper limit of normal (ULN), 2) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN * Adequate renal function as evidenced by serum creatinine (Cr)≤1.5 × ULN or creatinine clearance ≥60 mL/min. * Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening.
Exclusion criteria
* Any other malignancy within 5 years, with the exception of cured in-situ carcinoma or basal cell carcinoma etc. * Patients with distant metastases and/or cannot complete resection. * Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment. * Active HIV, HBV, HCV infection. * Combined with uncontrollable systemic diseases. * Presence of severe gastrointestinal disease (including active bleeding, \> grade 1 obstruction \[CTCAE v5.0\], or \> grade 1 diarrhea \[CTCAE v5.0\]). * History of allergy or hypersensitivity to drug or any of their excipients. * Patients who have chemotherapy and surgery contraindications. * Documented serum albumin ≤3 g/dL * Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1 within 14 days before the first administration. * Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception. * Participated in other trial within 30 days before the first administration. * Patients who are not suitable to participate in this trial for any reason judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| R0 resection rate | 4 months | Defined as the proportion of patients who have achieved R0 resection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Surgical Conversion Rate (R0 / R1 resection) | 4 months | Defined as the percentage of patients that underwent a R0/R1 resection. |
| Tumor regression grade | 4 months | The classification is mainly based on the proportion of residual tumors and fibrosis in the primary tumor, used to evaluate the patient's response to neoadjuvant therapy and predict prognosis. |
| Objective Response Rate | 3 months | Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1 |
| Overall survival | 2 years | Defined as the time between signing the informed consent form and death due to various causes. |
| Incidence of adverse events | 7 months | Use NCI-CTCAE version 5.0 for classification and grading. |
| Event-free Survival | 1 year | Defined as the time between signing the informed consent form to the first documentation of 1) disease progression (local recurrence, new lesions or distant metastasis), 2) a second malignant tumor occurs, or 3) death due to any cause. |
Contacts
Primary ContactChuntao Gao, Professor
Outcome results
None listed