Clinical trial NCT06259058: Stereotactic Body Radiation Therapy Followed by NALIRIFOX vs NALIRIFOX for Borderline Resectable Pancreatic Cancer
Official title: Evaluate the Efficacy and Safety of Stereotactic Body Radiation Therapy Followed by NALIRIFOX vs NALIRIFOX for Borderline Resectable Pancreatic Cancer: a Phase Ib/II, Multicenter, Open-label Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Keywords: borderline resectable
NALIRIFOX
stereotactic body radiation therapy
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2024-02-14
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: R0 resection rate
timeFrame: 4 months
Secondary outcomes:
measure: Objective Response Rate
timeFrame: 3 months
measure: Surgical Conversion Rate (R0 / R1 resection)
timeFrame: 4 months
measure: Tumor regression grade
timeFrame: 4 months
measure: Event-free Survival
timeFrame: 1 year
measure: Overall survival
timeFrame: 2 years
measure: Incidence of adverse events
timeFrame: 7 months
Other outcomes:
Locations:
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Jihui Hao, Professor
role: PRINCIPAL_INVESTIGATOR
References: