Trial Title:
Irinotecan Liposome in Combination With Capecitabine
NCT ID:
NCT06578052
Condition:
Pancreatic Cancer
Conditions: Official terms:
Pancreatic Neoplasms
Capecitabine
Irinotecan
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
"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
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Irinotecan liposome Capecitabine
Description:
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."
Arm group label:
Irinotecan liposome Capecitabine
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.
Detailed description:
This study is a prospective, multicenter, single-arm phase II study. It is expected to
include 20 patients with unresectable/metastatic pancreatic cancer who have relapsed
after standard treatment, and they will be treated with a regimen of liposomal irinotecan
combined with capecitabine. The main research unit is the Shenzhen Hospital of the
Chinese Academy of Medical Sciences Cancer Hospital. The study includes a screening
period (within 28 days), a treatment period (an estimated 6 cycles, until disease
progression or intolerable toxicity occurs), and a follow-up period (12 months for safety
follow-up and progression-free survival (PFS) follow-up). Participants sign an informed
consent form and undergo baseline examinations during the screening period. Patients who
meet the inclusion and exclusion criteria enter the treatment period, and all
participants complete the relevant examinations stipulated by the protocol during the
treatment process to observe safety, tolerability, and efficacy. The same participant
will only receive one dosing plan during the study period. After the end of the treatment
period, the follow-up period begins
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. patients were fully aware of the study, participated voluntarily and signed the
informed consent form (ICF);
2. aged ≥18 years and ≤80 years;
3. patients with histopathologically confirmed unresectable/metastatic pancreatic
cancer;
4. imaging-confirmed tumor progression after prior treatment with a standard first-line
regimen;
5. patients with at least one measurable target lesion according to RECIST 1.1
criteria;
6. Eastern Cooperative Oncology Group (ECOG) physical status score: 0-2;
7. expected survival time ≥ 3 months;
8. 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);
9. 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.
- Exclusion Criteria:
1. hypersensitivity to any of the study drugs or their components;
2. 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.);
3. cardiac function and disease consistent with one of the following conditions
1. Long QTc syndrome or QTc interval >480 ms;
2. Complete left bundle branch block, degree II or degree III atrioventricular
block;
3. Severe, uncontrolled arrhythmia requiring pharmacologic therapy;
4. New York Society of Cardiology classification ≥ grade III;
5. Cardiac ejection fraction (LVEF) less than 50%;
6. 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.
4. 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;
5. human immunodeficiency virus (HIV) infection (HIV-positive);
6. imaging confirmation of intestinal obstruction;
7. 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);
8. pregnant and lactating women and patients of childbearing age who do not wish to use
contraception;
9. patients with other malignant tumors requiring treatment;
10. patients who, in the judgment of the investigator, are not suitable for
participation in this study.
11. history of pulmonary hemorrhage/coughing up ≥ grade 2 (defined as at least 2.5 mL of
bright red blood) within 1 month prior to the first dose of drug;
12. a predisposition to arterial embolism, severe hemorrhage (other than bleeding due to
surgery), and severe bleeding within 6 months prior to first dose;
13. a combination of symptomatic brain metastases, meningeal metastases, spinal cord
tumor invasion, and spinal cord compression
14. use of strong inhibitors or inducers of CYP3A4, CYP2C8, and UGT1A1 within 14 days
prior to receiving study drug therapy
15. who have used other clinical trial medications within 1 month prior to the first
dose;
16. pregnant or lactating female patients, subjects of childbearing age who refuse to
accept contraception; -
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Start date:
August 20, 2024
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center
Agency class:
Other
Source:
Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06578052
