Liposomal Irinotecan + Oxaliplatin + Bevacizumab Versus Liposomal Irinotecan + 5-FU/LV

Liposomal Irinotecan in Combination With Oxaliplatin and Bevacizumab Versus Liposomal Irinotecan in Combination With 5-FU/LV for the Second-line Treatment of Advanced Pancreatic Cancer

Purpose of the study Phase I study: to explore the optimal dose combination of irinotecan liposome + oxaliplatin + bevacizumab regimen, irinotecan liposome + oxaliplatin Phase II study: to evaluate the safety and efficacy of the second-line treatment regimen of irinotecan liposome combined with oxaliplatin and bevacizumab compared to the second-line treatment regimen of irinotecan liposome combined with 5-FU/LV in advanced pancreatic cancer Sample size 138 cases Phase I Crawl, sample size 9-18 cases. Phase II randomized controlled clinical study, historical data NAPOLI-1 study, ORR of 8.8% for irinotecan liposome + 5-FU/LV, planned trial arm ORR upgrade to 25%, calculated at 60 cases in each arm.

Subject population Patients with advanced pancreatic cancer diagnosed after failure of first-line therapy, confirmed by histopathology or cytopathology, who meet the inclusion criteria and do not meet the exclusion criteria.

Phase I design:

Liposomal irinotecan + oxaliplatin + bevacizumab, 2-week regimen Liposomal irinotecan: start exploring with 50mg/m2 dose, preset 50mg/m2, 60mg/m2, 2 dose groups, 90min IV infusion, d1; Oxaliplatin: explored from 60mg/m2 dose, preset 60mg/m2, 85mg/m2, 2 dose groups, IV infusion, d1; Bevacizumab: 5 mg/kg, i.v., d1; Phase II study design.

Trial group:

Irinotecan liposomal: RP2D, i.v., 90min, d1; Oxaliplatin: RP2D, i.v., d1; Bevacizumab: 5mg/kg, i.v., d1; Cycles every 2 weeks until disease progression or intolerable; imaging every 3 treatment cycles/1.5 months.

Control:

Liposomal irinotecan: 70 mg/m2 IV for 90 min, d1; Calcium folinate: 400 mg/m2, IV infusion over 30 min, d1; 5-FU: 2400 mg/m2, continuous IV infusion over 46h; Cycles every 2 weeks until disease progression or intolerable; imaging every 3 treatment cycles/1.5 months.

Notes:

If the duration of irinotecan liposome infusion can be extended appropriately based on the patient's clinical response; if the patient withdraws from the trial due to intolerance of toxicity (e.g., neurotoxicity or myelotoxicity) induced by one of the drugs, follow up is required until PFS and OS.

Translated with DeepL.com (free version)

Study Overview

• Status: Recruiting
• Conditions: Advanced Pancreatic Cancer (Part 1)
• Intervention / Treatment: Drug: Irinotecan liposoma; Drug: oxaliplatin; Drug: bevacizumab; Drug: 5-FU; Drug: LV; Drug: Irinotecan Liposomal; Drug: Irinotecan Liposomal; Drug: Oxaliplatin

• Study Type: Interventional
• Enrollment (Estimated): 138
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Guanghai Dai; Phone Number: 13801232381; Email: daigh60@sohu.com
• Study Contact Backup: Name: Ru Jia; Phone Number: 13811721720; Email: ashleyjr@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Chinese PLA General Hospital
    • Contact: Guanghai Dai; Phone Number: 13801232381; Email: daigh60@sohu.com
  • Beijing, China
    • Not yet recruiting
    • Beijing

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 to 75 years old;
2. Patients with pancreatic cancer diagnosed by histopathology or cytology;
3. Unresectable disease assessed by multidisciplinary and imaging;
4. Subjects who have received prior failed first-line therapy, and recurrence within 6 months of the end of (neo)adjuvant therapy is considered a first-line treatment failure;
5. Subjects who have not received platinum-containing or irinotecan drugs for prior first-line therapy;
6. Patients with at least one evaluable lesion according to RECIST v1.1;
7. ECOG score of 0-2;
8. Expected survival ≥ 3 months;
9. Bone marrow function: absolute neutrophil count (ANC) ≥1.5×10^9/L, hemoglobin ≥90 g/dL, platelets (PLT) ≥100×10^9/L, and white blood cells (WBC) ≥3.0×10^9/L;
10. Liver function: alanine aminotransferase (ALT), alanine aminotransferase (AST), alkaline phosphatase (ALP) ≤2.5 times the upper limit of normal (ULN), or ≤5×ULN if liver metastases are present, total bilirubin<1.5 ULN;
11. Renal function: serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance (CCr) ≥60 mL/min (according to the Cockcroft-Gault formula);
12. Coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5 × ULN;
13. Patients with biliary obstruction should receive adequate biliary drainage; and
14. Adverse reactions arising from prior therapy must be restored to grade 1 or baseline according to CTCAE 5.0 (with the exception of toxicities such as alopecia, grade 2 or lower peripheral neuropathy, which can be enrolled with no safety risk in the judgment of the investigator);
15. Non-pregnant or lactating females; females/males of childbearing potential should use effective contraception during the study and for 6 months after completion of study treatment;
16. Patients are compliant, understand the study procedures, and sign a written informed consent form.

Exclusion Criteria:

1. Patients who have had other malignant tumors within the previous 5 years (except cured carcinoma in situ and basal cell carcinoma of the skin);
2. Uncontrollable pleural effusion or ascites;
3. Any known brain metastasis or meningeal metastasis;
4. Concomitant use of a potent CYP3A4 inducer within 3 weeks prior to the first dose, or concurrent use of a potent CYP3A4 inhibitor or potent UGT1A1 inhibitor within 3 weeks prior to the first dose;
5. Patients undergoing major organ surgery (except needle biopsy, central venous catheterization, port catheterization, stent placement for relief of biliary obstruction, percutaneous hepato-biliary drainage, cholecystostomy) or elective surgical procedures scheduled within 4 weeks prior to the first dose of study drug;
6. Systemically treated active, uncontrolled bacterial, viral, or fungal infections, defined as persistent signs/symptoms associated with the infection that do not improve despite appropriate antibiotics, antiviral therapy, and/or other treatments;
7. Subjects with congenital or acquired immunodeficiency, such as HIV-infected individuals or active hepatitis (transaminases do not meet the inclusion criteria, Hepatitis B : HBV DNA ≥ 1000 IU/ml; Hepatitis C : HCV RNA ≥ 1000 IU/ml); chronic hepatitis B viral carriers, with HBV DNA < 2000 IU/ml, who must be concurrently receiving antiviral during the trial period treatment before enrollment;
8. Presence of serious concomitant diseases: those with diabetes mellitus that cannot be well controlled by glucose-lowering drugs, difficult-to-control hypertension, severe cardiovascular and cerebral vascular disease, renal failure, hepatic failure, uncontrolled epilepsy, central nervous system disease or history of mental disorders, those with a clear tendency to gastrointestinal bleeding, intestinal paralysis, intestinal obstruction, etc;
9. >grade 1 diarrhea with an increase in the number of bowel movements >4 times per day compared to baseline; moderate to severe increase in stoma discharge; limited instrumental activities of daily living or even limited spontaneous activities of daily living; life-threatening; requiring urgent treatment;
10. Those with serum albumin ≤ 3 g/dL;
11. Those who had participated in other clinical studies within 4 weeks prior to enrollment;
12. Patients assessed by the investigator to be unsuitable for participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Irinotecan liposomal combination of oxaliplatin and bevacizumab; To explore the optimal dose combination of irinotecan liposomes plus oxaliplatin in the regimen of irinotecan liposomes plus oxaliplatin in bevacizumab and determine the recommended dose for phase II	Drug: Irinotecan liposoma; Exploration started with 50mg/m^2 dose, preset 50mg/m^2, 60mg/m^2, 2 dose groups, IV infusion 90min, d1; Drug: oxaliplatin; Exploration started with 60mg/m^2 dose, preset 60mg/m^2, 85mg/m^2, 2 dose groups, IV infusion, d1; Drug: bevacizumab; 5mg/kg，i.v.，d1
Active Comparator: Irinotecan liposomal combination of 5-FU/LV; Standard treatment	Drug: 5-FU; 2400mg/m^2, i.v.，46h; Drug: LV; 400mg/m^2, i.v.，d1; Drug: Irinotecan Liposomal; 70mg/m^2, i.v.，d1; Drug: Irinotecan Liposomal; Phase II recommended dose
Experimental: Irinotecan liposomal +oxaliplatin +bevacizumab; Phase II recommended dose	Drug: bevacizumab; 5mg/kg，i.v.，d1; Drug: Irinotecan Liposomal; 70mg/m^2, i.v.，d1; Drug: Irinotecan Liposomal; Phase II recommended dose; Drug: Oxaliplatin; Phase II recommended dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To explore the optimal dose combination of irinotecan liposomes plus oxaliplatin in the regimen of irinotecan liposomes plus oxaliplatin in bevacizumab	The DLT determination criteria are as follows: Hematologic toxicity：Grade 4 neutropenia with application of granulocyte colony-stimulating factor still persisting for >3 days ;Grade 3 or above FN;Grade 3 thrombocytopenia with bleeding and/or need for blood transfusion;Grade 4 thrombocytopenia;Grade 4 anemia.; Non-hematologic toxicity： ≥ Grade 3 non-hematologic toxicity, except: ① Transient (≤24 hours) Grade 3 fever (>40°C), Grade 3 malaise, Grade 3 headache, Grade 3 nausea, which recovers to Grade 1 or baseline after treatment; Grade 3 vomiting, Grade 3 electrolyte disorders (including hypokalemia, hypophosphatemia, hypocalcemia, etc.), recovery to Grade 1 or baseline within 48 hours after treatment.	At the end of Cycle 1 (each cycle is 14 days)

Collaborators and Investigators

• Sponsor: Dai, Guanghai

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: October 10, 2024
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Oxaliplatin; Bevacizumab; Irinotecan; Camptothecin
• Other Study ID Numbers: CSPC-DNY-PC-B01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No