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

NCT ID: NCT06699459

Last Updated: 2024-11-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-14
• Study Completion Date: 2026-11-15

Brief Summary

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.

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.

Conditions

Biliary Tract Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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;

Group Type: EXPERIMENTAL

Irinotecan Liposome

Intervention Type: DRUG

②LV: 400mg/m2, intravenous infusion, Q2W, d1; ③5-FU: 2400 mg/m2, continuous intravenous infusion, Q2W, d1-2;

Capecitabine

Capecitabine, 1250mg/m2 oral, bid, Q3W, d1-14;

Group Type: OTHER

Capecitabine

Intervention Type: DRUG

① Capecitabine, 1250mg/m2 orally, bid, Q3W, d1-14;

Interventions

Irinotecan Liposome

②LV: 400mg/m2, intravenous infusion, Q2W, d1; ③5-FU: 2400 mg/m2, continuous intravenous infusion, Q2W, d1-2;

Intervention Type: DRUG

Capecitabine

① Capecitabine, 1250mg/m2 orally, bid, Q3W, d1-14;

Intervention Type: DRUG

Other Intervention Names

Irinotecan Liposome+LV/5-FU

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhejiang Cancer Hospital

OTHER

Sponsor Role: collaborator

RenJi Hospital

OTHER

Sponsor Role: collaborator

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: collaborator

Fujian Provincial Hospital

OTHER

Sponsor Role: collaborator

Ningbo No. 1 Hospital

OTHER

Sponsor Role: collaborator

Shaoxing People's Hospital

OTHER

Sponsor Role: collaborator

Southern Medical University, China

OTHER

Sponsor Role: collaborator

First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: collaborator

Sir Run Run Shaw Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mingyu Chen, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Sir Run Run Shaw Hospital

Locations

Fujian Provincial Hospital

Fuzhou, Fujian, China

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Renji Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Sir Run Run Shaw Hospital , affiliated with the Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Countries

China

Central Contacts

Mingyu Chen, Ph.D

Role: CONTACT

mychen@zju.edu.cn

0086-18757772223

Ruijing Shen, Master

Role: CONTACT

22418542@zju.edu.cn

0086-17706431287

Facility Contacts

Shi Chen

Role: primary

Wei Chen

Role: primary

Maolang Li, Ph.D

Role: primary

Xiangsong Wu

Role: primary

Yuhua Zhang, Ph.D

Role: primary

Mingyu Chen, Ph.D

Role: primary

mychen@zju.edu.cn

0086-18757772223

Ruijing Shen, Master

Role: backup

22418542@zju.edu.cn

0086-17706431287

Other Identifiers

SRRSH.20240559

Identifier Type: -

Identifier Source: org_study_id