Clinical trial NCT06345300: NALIRIFOX in Combination With Camrelizumab for BRPC: a Prospective, Exploratory Study
Official title: Liposomal Irinotecan，Oxaliplatin, 5-Fluorouracil/Calcium Folinate in Combination With Camrelizumab for Borderline Resectable Pancreatic Cancer: a Prospective, Exploratory Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Borderline Resectable Pancreatic Cancer
Keywords: Liposomal Irinotecan
borderline resectable pancreatic cancer
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2024-04-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess the efficacy and safety of Liposomal Irinotecan, Oxaliplatin, 5-Fluorouracil/Calcium folinate in combination with Camrelizumab for patients with borderline resectable pancreatic cancer

Detailed description: This study plans to include 40 patients with borderline resectable pancreatic cancer who are evaluated by a multidisciplinary team (MDT). These patients will receive 3 cycles of neoadjuvant therapy before surgery. The immunotherapy combination chemotherapy regimen consists of liposomal Irinotecan, Oxaliplatin, 5-Fluorouracil/Calcium folinate, and Camrelizumab, with a 14-day dosing cycle. The chemotherapy regimen consists of liposomal Irinotecan, Oxaliplatin, and 5-Fluorouracil/Calcium folinate.

Clinical tumor imaging evaluation will be conducted based on the RECIST 1.1 criteria after the completion of neoadjuvant therapy. The MDT will assess whether patients are eligible for surgery based on the imaging results. The criteria for operability include: no evidence of implantation metastasis during laparoscopic exploration, absence of new metastatic lesions, and the tumor's relationship with blood vessels meeting the criteria for R0/R1 resection.

Patients eligible for surgery will undergo pancreatic cancer surgery 4-6 weeks later. Postoperative treatment will be determined by the researchers based on the neoadjuvant treatment effectiveness and the patients'actual conditions. Imaging evaluations will follow the standard diagnostic and treatment guidelines for pancreatic cancer.

For patients deemed ineligible for surgery, the subsequent treatment plan will be determined by the researchers based on the neoadjuvant treatment effectiveness and the patients' actual conditions

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years, both males and females are eligible.
2. Histologically or cytologically confirmed pancreatic cancer (originating from pancreatic duct epithelium) assessed by Multidisciplinary Team (MDT) as potentially resectable pancreatic cancer. (According to CSCO guidelines 2022, potentially resectable pancreatic cancer is defined as:Tumor involvement with the portal vein-mesenteric vein \>180° or contact ≤180° with irregular vein contour or vein thrombosis, but can be completely resected and safely reconstructed; tumor involvement with the inferior vena cava;(Tumor involving the pancreatic head/uncinate process) Tumor involvement with the hepatic artery distal to the celiac trunk, with no involvement of the celiac trunk or the origin of the left or right hepatic artery, can be completely resected and safely reconstructed; tumor involvement with the mesenteric artery ≤180°; tumor involvement with variant arteries (such as accessory right hepatic artery, replaced right hepatic artery, replaced common hepatic artery, etc.).(Tumor involving the body and tail of the pancreas) Tumor involvement with the mesenteric artery ≤180°; tumor involvement with the celiac trunk ≤180°).
3. No prior treatment with local or systemic anti-tumor therapy, including chemotherapy, radiation therapy, targeted therapy, or immunotherapy.
4. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Expected survival of ≥12 weeks.
7. Adequate organ function as follows (no use of any blood components, growth factors, leukocyte-boosting agents, platelet-boosting agents, or anemia correction drugs within 14 days prior to the first use of study medication):

   1. Absolute neutrophil count (ANC) ≥1.5×10\*9/L;
   2. Platelets ≥85×10\*9/L;
   3. Hemoglobin ≥90 g/L;
   4. Serum albumin ≥30 g/L;
   5. Total bilirubin ≤2.0 × upper limit of normal (ULN) (patients with biliary obstruction after biliary drainage ≤2.5 × ULN), AST and ALT ≤3.0 × ULN (patients with liver metastasis ≤5 × ULN);
   6. Creatinine clearance \> 60 mL/min;
   7. Activated partial thromboplastin time (APTT) and International Normalized Ratio (INR) ≤1.5 × ULN (patients taking stable doses of anticoagulants such as low molecular weight heparin or warfarin and INR within the expected therapeutic range of the anticoagulant can be included).
8. Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days before enrollment and agree to use appropriate contraception during the observation period and up to 8 weeks after the last administration of the study drug; for males, they must have undergone surgical sterilization or agree to use appropriate contraception during the observation period and up to 12 weeks after the last administration of the study drug.
9. Participate in the study and signing of an informed consent form.

Exclusion Criteria:

* Participants who meet any of the following criteria will not be allowed to enter this study:

  1. Pancreatic cancer originating from non-pancreatic ductal epithelium, including pancreatic neuroendocrine tumors, pancreatic acinar cell carcinoma, pancreatic embryonal carcinoma, solid pseudo-papillary tumors.
  2. Patients with central nervous system metastasis.
  3. Severe gastrointestinal dysfunction (with bleeding, inflammation, obstruction, or diarrhea classified as grade 1 or higher).
  4. Existence of grade 3 or 4 peripheral neuropathy.
  5. Presence of uncontrollable pleural effusion, pericardial effusion, or ascites requiring drainage.
  6. Uncontrolled systemic infection (viral, bacterial, and fungal).
  7. Allergy to previous use of erlotinib liposomes, other liposomal products, oxaliplatin, 5-fluorouracil, calcium folinate, or any component of the mentioned products.
  8. Allergy to monoclonal antibodies, camrelizumab, or any component of the investigational drug.
  9. Use of any investigational drug within 4 weeks prior to the first use of the investigational drug in this study.
  10. Receipt of the last dose of anticancer therapy (including radiotherapy) within 4 weeks prior to the first use of the investigational drug.
  11. Underwent major surgery within 4 weeks prior to the first use of the investigational drug.
  12. Concurrent participation in another clinical study, unless it is an observational (non-interventional) clinical study or follow-up of an interventional clinical study.
  13. Participants with poorly controlled cardiovascular clinical symptoms or diseases, including but not limited to: (1) NYHA class II or higher heart failure; (2) unstable angina pectoris; (3) myocardial infarction within the past year.
  14. Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL) or hepatitis C (positive anti-HCV or HCV-RNA above the detection limit of the assay).
  15. Diagnosed with any other malignant tumor within 5 years prior to the first use of the investigational drug, excluding malignant tumors with low risk of metastasis and death (5-year survival rate \> 90%), such as adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix.
  16. Pregnant or lactating women.
  17. Participant judged by the investigator to have other factors that may necessitate premature termination of the study, such as the presence of other serious diseases (including mental illnesses) requiring concurrent treatment, or family or social factors that may affect participant safety or data collection in the study.
  18. Other factors deemed by the investigator to make the participant unsuitable for participation in this study.

Primary outcomes:
measure: R0 resection rate
timeFrame: 1 years
Secondary outcomes:
measure: Event free survival (EFS)
timeFrame: 1.5 years
measure: Overall survival (OS)
timeFrame: 2 years
measure: Objective Response Rate(ORR)
timeFrame: 2year
measure: Disease Control Rate（DCR）
timeFrame: 2 years
measure: Safety and tolerability by incidence, severity and outcome of adverse events
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijin
country: China
facility: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study officials:
References: