Irinotecan Liposome in Combination With Capecitabine

NCT06578052 | Recruiting DMC

• 1 other identifier: YW 2024-43
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Pancreatic cancer is a group of malignant tumors mainly originated from pancreatic ductal epithelium and follicular cells, with high degree of malignancy, insidious onset, difficult early diagnosis, rapid progression, short survival time, and one of the malignant tumors with the worst prognosis, which is known as the "king of cancers". In recent years, the incidence rate of pancreatic cancer has been increasing both at home and abroad. At present, the palliative treatment of advanced pancreatic cancer is still mainly based on chemotherapy, such as FOLFIRINOX regimen. And after standard first-line treatment, most of the patients have problems such as poor physical status, no standard treatment options and limited options available. Capecitabine is a selective fluorouracil methionine salt antitumor drug, belongs to the pyrimidine class of antimetabolites, and is the precursor drug of 5-fluorouracil. Its first-line monotherapy for pancreatic cancer is 24% effective, and it is directly recommended by NCCN 2024 V2.0 as a second-line treatment for patients with pancreatic cancer who have failed gemcitabine therapy.The 2024 CSCO Guidelines for Pancreatic Cancer recommend the use of 5-fluorouracil (5-FU)-like regimens as a second-line treatment for patients who have been treated with a gemcitabine-based regimen as first-line treatment. In a clinical study exploring capecitabine in gemcitabine-treated patients with metastatic or unresectable locally advanced pancreatic cancer, 42 patients received oral capecitabine 1,250 mg/m2 twice daily (2,500 mg/m2/d) as intermittent therapy in 3-week cycles consisting of 2 weeks of dosing followed by 1 week of withdrawal. A total of 4 remissions were achieved in 42 evaluable patients, for an overall remission rate of 9.5%. Irinotecan Hydrochloride Liposome Injection, the first domestic generic product developed by Shiyao Group, was launched in China in September 2023 with an approved indication for use in combination with 5-FU and calcium folinate (LV) in patients with metastatic pancreatic cancer that has progressed after treatment with gemcitabine. Liposomal irinotecan hydrochloride has been studied in a number of indications including biliary tract cancer, colorectal cancer, glioma, gastric cancer, small cell lung cancer, cervical cancer, breast cancer, head and neck cancer, esophageal cancer, and neuroendocrine cancer. In the bioequivalence trial of Shiyi Group's irinotecan hydrochloride liposome injection, the ORR rate reached 12.9%, the median PFS was 6.24 months, and the median OS was 10.38 months; indicating similar efficacy and a similar safety profile. A randomized, open-label, phase 3 NAPOLI 3 study and the first phase 3 trial comparing two combination chemotherapy regimens in the first-line treatment of patients with pancreatic ductal carcinoma head-to-head was designed to compare the efficacy and safety differences between the NALIRIFOX regimen (irinotecan liposomal, fluorouracil, and calcium folinic acid in combination with oxaliplatin) versus the doublet regimen (gemcitabine + albumin-conjugated paclitaxel) in the first-line treatment of metastatic pancreatic ductal carcinoma efficacy and safety differences in the treatment of metastatic pancreatic ductal cancer. The results showed that the median OS in the NALIRIFOX treatment group was 11.1 months, while the median OS in the dual combination treatment group was 9.2 months (HR=0.83; 95% CI 0.70-0.99; p=0.036). Based on the above literature research, combined with the efficacy and safety advantages of irinotecan liposome chemotherapy combination regimen in patients with metastatic pancreatic cancer, we propose to carry out a phase II clinical study of irinotecan liposome combined with capecitabine in the second-line treatment of advanced pancreatic cancer. The aim is to explore the efficacy and safety of irinotecan liposomal chemotherapy combined with capecitabine in second-line unresectable or metastatic pancreatic cancer patients, and to explore more effective clinical options for patients with pancreatic cancer that has progressed after previous treatment.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-Free Survival (PFS)

  TFrom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

Secondary Outcomes (3)

• Objective Response Rate

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

• Disease Control Rate

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

• Overall Survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

Study Arms (1)

Irinotecan liposome Capecitabine

OTHER

Irinotecan liposome: intravenous infusion, day 1, every 2 weeks (Q2W). Capecitabine: oral, twice daily (bid), days 1 to 7, take for one week and then have a one-week interval. Each 2-week period is considered a treatment cycle, with an expected treatment of 6 cycles. Subsequent maintenance treatment will be determined by the investigator's protocol until disease progression or intolerable toxicity occurs."

Drug: Irinotecan liposome Capecitabine

Interventions

Irinotecan liposome Capecitabine DRUG

Irinotecan liposome: intravenous infusion, day 1, every 2 weeks Capecitabine: oral, twice daily (bid), days 1 to 7, take for one week and then have a one-week interval. Each 2-week period is considered a treatment cycle, with an expected treatment of 6 cycles. Subsequent maintenance treatment will be determined by the investigator's protocol until disease progression or intolerable toxicity occurs."

Irinotecan liposome Capecitabine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients were fully aware of the study, participated voluntarily and signed the informed consent form (ICF);
• aged ≥18 years and ≤80 years;
• patients with histopathologically confirmed unresectable/metastatic pancreatic cancer;
• imaging-confirmed tumor progression after prior treatment with a standard first-line regimen;
• patients with at least one measurable target lesion according to RECIST 1.1 criteria;
• Eastern Cooperative Oncology Group (ECOG) physical status score: 0-2;
• expected survival time ≥ 3 months;
• absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, platelets ≥ 100 x 10\^9/L and hemoglobin ≥ 90 g/L (not transfused with blood, blood products, or corrected with granulocyte colony-stimulating factor or other hematopoietic-stimulating factor in the 14 days prior to the laboratory test);
• Liver and kidney function: serum creatinine ≤1.5 times the upper limit of normal value; AST and ALT ≤2.5 times the upper limit of normal value.
• Liver and kidney function: serum creatinine ≤1.5 times the upper limit of normal value; AST and ALT ≤2.5 times the upper limit of normal value (≤5 times the upper limit of normal value for patients with liver metastases); total bilirubin ≤1.5 times the upper limit of normal value (≤3 times the upper limit of normal value for patients with liver metastases); 10. Women of childbearing potential must have had a negative pregnancy test (serum) within 7 days prior to enrollment and be willing to use an appropriate method of contraception for the duration of the trial and for 6 months after the last administration of the test drug.

You may not qualify if:

• hypersensitivity to any of the study drugs or their components;
• concomitant serious uncontrolled concurrent infections or other serious uncontrolled concomitant diseases, moderate or severe renal impairment; (e.g., progressive infections, uncontrollable hypertension, diabetes mellitus, etc.);
• cardiac function and disease consistent with one of the following conditions
• Long QTc syndrome or QTc interval \>480 ms;
• Complete left bundle branch block, degree II or degree III atrioventricular block;
• Severe, uncontrolled arrhythmia requiring pharmacologic therapy;
• New York Society of Cardiology classification ≥ grade III;
• Cardiac ejection fraction (LVEF) less than 50%;
• History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, history of clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormality within 6 months prior to recruitment.
• active hepatitis B or C infection (hepatitis B virus surface antigen positive and hepatitis B virus DNA greater than 1x103 copies/mL; hepatitis C virus RNA greater than 1x103 copies/mL), except for asymptomatic chronic hepatitis B or hepatitis C carriers;
• human immunodeficiency virus (HIV) infection (HIV-positive);
• imaging confirmation of intestinal obstruction;
• previous or current concurrent other malignancies (except effectively controlled non-melanoma basal cell carcinoma of the skin, carcinoma in situ of the breast/cervix, and other malignancies that have been effectively controlled without treatment within the past five years);
• pregnant and lactating women and patients of childbearing age who do not wish to use contraception;
• patients with other malignant tumors requiring treatment;

Sponsors & Collaborators

• Junjie Hang: lead

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center

Shenzhen, Guangdong, 518100, China

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Central Study Contacts

Junjie Hang, M.D.

CONTACT

+86-13681709736; hjj199141@alumni.sjtu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate chief physician

Model Details: "Irinotecan liposome: intravenous infusion, day 1, every 2 weeks (Q2W). Capecitabine: oral, twice daily (bid), days 1 to 7, take for one week and then have a one-week interval. Each 2-week period is considered a treatment cycle, with an expected treatment of 6 cycles. Subsequent maintenance treatment will be determined by the investigator's protocol until disease progression or intolerable toxicity occurs

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 29, 2024
• Study Start: August 28, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 14, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)