Irinotecan Liposomes +5-FU/LV Versus Capecitabine in Patients of Recurrence After Resection of Resectable BTC (NICRRBTC)

Irinotecan Liposomes +5-FU/LV or Capecitabine in Patients at High Risk of Recurrence After Resection of Resectable Biliary Tract Carcinoma: A Prospective Phase II Study

Irinotecan liposome combined with 5-FU/LV has shown good efficacy and has certain advantages in reducing the adverse reactions of conventional chemotherapy drugs. Adjuvant treatment of high-risk factors after surgery for biliary tract tumors can be further explored and attempted. Therefore, this study intends to conduct an exploratory study comparing oral capecitabine with irinotecan liposome +5-FU/LV for adjuvant therapy in high-risk patients after resection of resectable biliary malignancies, and evaluate the effectiveness and safety of irinotecan liposome +5-FU/LV as adjuvant therapy for high-risk patients after resection of resectable biliary malignancies. So it can provide more treatment options for patients with postoperative adjuvant therapy of biliary tract malignant tumor.

The DFS rate one year after surgery for biliary malignancy was assumed to be 51.4% with a maximum response rate of poor efficacy and 71.4% with a minimum response rate of good efficacy. A two-stage design was adopted with α=0.05 and certainty (1-β) =0.8, and Minimax was adopted. If a response occurs in 7 out of 14 patients or less, treatment options are rejected; In the second phase, if 24 or fewer responses occur in 38 patients, the protocol is rejected. A total of 38 samples were designed in two stages. The 1-year DFS rate was at least 65.8% in the total population of the test and control groups.

Study Overview

• Status: Not yet recruiting
• Conditions: Biliary Tract Carcinoma
• Intervention / Treatment: Drug: Irinotecan Liposome; Drug: Capecitabine

Detailed Description

According to the 2023 CSCO guidelines, differentiated surgical treatment has been performed for the site of biliary malignancies. For postoperative adjuvant therapy, BILCAP study showed that oral capecitabine as a single drug is one of the options for both efficacy and safety. For patients with postoperative risk factors, serum carcinoembryonic antigen (CEA) and CA19-9 are of some significance for monitoring recurrence, and often serve as precursors for clinical judgment of recurrence or progression. For people with high risk factors for recurrence and progression, adjuvant therapy intensity needs to be strengthened. Oral capecitabine can no longer meet the needs of this population, so patients need to be given intravenous chemotherapy in advance to control progression, recurrence or metastasis. In this case, metastatic first-line therapy is often used for early intervention. The NIFE study showed that compared with conventional chemotherapy regimens, the regimen of irinotecan liposome (new formulation) combined with 5-FU/LV achieved relatively better efficacy data in the median OS and ORR efficacy. It is noteworthy that this regimen has a significant therapeutic benefit in patients with advanced first-line extrahepatic cholangiocarcinoma, with a median PFS of 9.59 months and a median OS of 18.23 months.

To explore the efficacy and safety of irinotecan liposomes +5-FU/LV versus oral capecitabine in patients at high risk of recurrence after resection of resectable biliary malignancies.

• Study Type: Interventional
• Enrollment (Estimated): 76
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mingyu Chen, Ph.D; Phone Number: 0086-18757772223; Email: mychen@zju.edu.cn
• Study Contact Backup: Name: Ruijing Shen, Master; Phone Number: 0086-17706431287; Email: 22418542@zju.edu.cn

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350028
      • Fujian Provincial Hospital
      • Contact: Shi Chen
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun Yat-sen University
      • Contact: Wei Chen
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Xiangsong Wu
    • Shanghai, Shanghai, China, 200001
      • Renji Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Maolang Li, Ph.D
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Zhejiang Cancer Hospital
      • Contact: Yuhua Zhang, Ph.D
    • Hangzhou, Zhejiang, China, 310009
      • Sir Run Run Shaw Hospital , affiliated with the Zhejiang University School of Medicine
      • Contact: Mingyu Chen, Ph.D; Phone Number: 0086-18757772223; Email: mychen@zju.edu.cn
      • Contact: Ruijing Shen, Master; Phone Number: 0086-17706431287; Email: 22418542@zju.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18-75 years old.
• Patients with histologically confirmed, resectable biliary malignancies with R0 resection.
• Postoperative pathology indicated the following risk factors: positive lymph nodes, vascular invasion, nerve invasion and so on.
• Has not received systemic chemotherapy before.
• The ECOG score is 0 to 1.
• Bone marrow and organ function were good: ① Neutrophils (ANC) ≥1.5×109/L, platelets (PLT) ≥100×109/L, hemoglobin (Hb) ≥90g/L, white blood cells (WBC) ≥3.0×109/L, albumin (ALB) ≥32 g/L, and no bleeding tendency; ② Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤2.5× upper limit of normal range (ULN), ≤5×ULN with liver metastasis; Total bilirubin ≤1.5×ULN; Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 mL/min (calculated according to Cockroft-Gault).
• Expected survival ≥3 months.
• Volunteer to participate in the study and sign the informed consent. If the subject does not have the ability to read the informed consent (e.g., illiterate subjects), a witness must witness the informed process and sign the informed consent.

Exclusion Criteria:

• Patients allergic to the investigational drug and its excipients.
• Known or suspected central nervous system or lymphatic metastasis.
• Cannot discontinue use or has not discontinued use of CYP3A, CYP2C8, and UGT1A1 potent depressants or inducers (e.g., anticonvulsants [phenytoin, phenobarbital, or carbamazepine] within 2 weeks prior to enrollment), rifampicin, rifambutin, St.John's Wort, Grapefruit juice, clarithromycin, Itraconazole, Lopinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Terrapivir, voriconazole, Azanavir, Gefilozil, Indinavir, etc.).
• There are signs and symptoms of intestinal obstruction.
• Other malignancies within the past 5 years or currently, except for cured cervical carcinoma in situ, uterine carcinoma in situ, and non-melanoma skin cancers.
• Autoimmune disease or long-term steroid use.
• Patients who are pregnant or nursing women, and patients who refuse to receive contraception during their reproductive age.
• Patients deemed unsuitable for participation in this study.
• Vulnerable groups, including people with mental illness, cognitive impairment, critically ill patients, etc.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Irinotecan liposome; Irinotecan liposomes: 70mg/m2, intravenous infusion, Q2W, d1; ②LV: 400mg/m2, intravenous infusion, Q2W, d1; ③5-FU: 2400 mg/m2, continuous intravenous infusion, Q2W, d1-2;	Drug: Irinotecan Liposome; ②LV: 400mg/m2, intravenous infusion, Q2W, d1; ③5-FU: 2400 mg/m2, continuous intravenous infusion, Q2W, d1-2; Other Names: Irinotecan Liposome+LV/5-FU
Other: Capecitabine; Capecitabine, 1250mg/m2 oral, bid, Q3W, d1-14;	Drug: Capecitabine; ① Capecitabine, 1250mg/m2 orally, bid, Q3W, d1-14;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
one year DFS rate	The percentage of patients free of disease when the disease-free survival is at the 1-year node	From date of randomization until the date of one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Time from initiation of treatment to first recording of PD or death	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Overall survival	The time between the start of treatment and the first recorded death	From date of randomization until the date of death from any cause, assessed up to 24 months
Disease-free survival	From randomization to the time when the first tumor recurred or metastasized, or when the subject died for any reason	From date of randomization until the date of first tumor recurred or metastasized or date of death from any cause, whichever came first, assessed up to 24 months
adverse events	Incidence and severity of adverse events in treatment regimens	Incidence and severity of adverse events in treatment regimens up to 24 months

Collaborators and Investigators

• Sponsor: Sir Run Run Shaw Hospital
• Collaborators: Zhejiang Cancer Hospital; First Affiliated Hospital, Sun Yat-Sen University; RenJi Hospital; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shaoxing People's Hospital; Southern Medical University, China; Ningbo No. 1 Hospital; Fujian Provincial Hospital
• Investigators: Principal Investigator: Mingyu Chen, Ph.D, Sir Run Run Shaw Hospital, affiliated with the Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): November 14, 2024
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): November 15, 2026

Study Registration Dates

• First Submitted: November 13, 2024
• First Submitted That Met QC Criteria: November 20, 2024
• First Posted (Estimated): November 21, 2024

Study Record Updates

• Last Update Posted (Estimated): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Capecitabine; Resectable; Adjuvant treatment; Biliary Tract Carcinoma; Irinotecan liposomes
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Recurrence; Carcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Capecitabine; Irinotecan
• Other Study ID Numbers: SRRSH.20240559

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Decide whether to share research data after publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No