Trial Title:
Adebelimab Combined With Irinotecan Liposomal Injection, Oxaliplatin, Fluorouracil and Calcium Folinate Are Used in the First-line Treatment of Pancreatic Cancer Liver Metastasis Efficacy and Safety
NCT ID:
NCT06531278
Condition:
Pancreatic Cancer Metastatic to Liver
Conditions: Official terms:
Pancreatic Neoplasms
Leucovorin
Oxaliplatin
Fluorouracil
Irinotecan
Calcium
Levoleucovorin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Irinotecan liposome
Description:
- Patients are planned to receive irinotecan liposomal (60 mg/m2; d1) of every cycle.
- 27 days a cycle
Arm group label:
first-line treatment of pancreatic cancer liver metastasis efficacy and safety
Intervention type:
Drug
Intervention name:
Adebrelimab
Description:
- Patients are planned to receive Adebrelimab (20 mg/kg; d1) of every cycle.
- 27 days a cycle
Arm group label:
first-line treatment of pancreatic cancer liver metastasis efficacy and safety
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
- Patients are planned to receive Oxaliplatin (85 mg/m2; d1) of every cycle.
- 27 days a cycle
Arm group label:
first-line treatment of pancreatic cancer liver metastasis efficacy and safety
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
- Patients are planned to receive fluorouracil (2400mg/m2; d1) of every cycle.
- 27 days a cycle
Arm group label:
first-line treatment of pancreatic cancer liver metastasis efficacy and safety
Intervention type:
Drug
Intervention name:
Calcium folinate
Description:
- Patients are planned to receive Calcium folinate (400mg/m2; d1) of every cycle.
- 27 days a cycle
Arm group label:
first-line treatment of pancreatic cancer liver metastasis efficacy and safety
Summary:
1. Evaluation of adebelimab in combination with irinotecan liposomes, oxaliplatin,
fluorouracil, efficacy and safety of leucovorin in the first-line treatment of
advanced metastatic pancreatic cancer
2. Construct the model of immunotherapy combined with chemotherapy for the treatment of
pancreatic cancer liver metastasis
Detailed description:
Pancreatic cancer is a cancer of the digestive system with a very high degree of
malignancy and a very poor prognosis. In recent years, morbidity and death. The rate
shows a clear upward trend at home and abroad. Global cancer statistics in 2020 show that
there are new pancreas cases worldwide each year. There are about 495,000 cases of
adenocarcinoma and about 466,000 deaths from pancreatic cancer each year. Statistical
tables for 2020. In the United States, there are about 57,600 new cases of pancreatic
cancer every year, and about 47,050 deaths due to pancreatic cancer each year. Data from
pancreatic cancer collected by the National Cancer Center of China in 2019. show that the
incidence of pancreatic cancer in Chinese is:6.92 per 100,000, with new cases accounting
for about 4.31% of all malignant tumors; The case fatality rate is 6.16 per 100,000 and
deaths per year Cases account for about 3.78% of all malignancies. The specific etiology
and pathogenesis of pancreatic cancer are unclear, and most (85%). It is an
adenocarcinoma originating from the ductal epithelium. Early symptoms are atypical, and
most patients are diagnosed locally advanced or out. Now distant metastasis. In the past
decade, the first-line treatment regimen for pancreatic cancer has been AG, FOLFIRINOX,
GS as the commonly used chemotherapy regimens, and the median OS was 8.5 months, 11.1
months, and 10.1 months, respectively. First-line treatment for pancreatic cancer still
needs to be explored. The advent of plastid Iriconia has changed the landscape of
first-line treatments, and the NAPOLI-3 study compared NALIRINOX (liposome irinotecan,
oxaliplatin, fluorouracil, leucovorin) and AG regimens in the first-line treatment of
metastatic pancreatic cancer and safety, with a median follow-up of 16.1 months, showed
that the median OS of NALIRINOX versus AG was respectively 11.1 versus 9.2 months (HR
0.83 [95% CI 0.70-0.99]; p=0.036), and the median PFS was 7.4 vs. 5.6, respectively
months (HR 0.69 [0.58-0.83]; p<0.0001), the ORR was 42% and 36%, respectively. Based on
this research The FDA approved liposomal irinotecan in combination with oxaliplatin,
fluorouracil, and leucovorin for the first-line treatment of metastatic pancreas
Indications for adenocarcinoma.
Jiangsu Hengrui Pharmaceutical Co., Ltd. developed irinotecan hydrochloride liposome
injection (HR070803) has both protection Protective, long-term cyclic and passively
targeted. HR070803 combination with 5-FU/LV for second-line treatment of locally advanced
or metastatic pancreas after failure of gemcitabine therapy Adenocarcinoma. Significantly
prolonged the subject's OS compared to placebo in combination with 5-FU/LV, with a
clinically meaningful difference, Significantly lower risk of death. In addition,
HR070803 in combination with 5-FU/LV may also prolong the subject's PFS and TTF, and
improve ORR and CA19-9 response rates. At the same time, HR070803 combined with 5-FU/LV
in advanced pancreas. The type of AE observed in the treatment of adenocarcinoma is
consistent with that of regular irinotecan, and there are gastrointestinal reactions,
hematotoxic. It is less sexual, well tolerated, and safe and controllable.
Based on the above evidence, this study explored the efficacy and safety of adebelimab,
irinotecan liposome, oxaliplatin, fluorouracil, and leucovorin in the first-line
treatment of advanced metastatic pancreatic cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients voluntarily join this study and sign the informed consent form
2. Age: 18-75 years old (inclusive), male or female
3. Histologically confirmed pancreatic cancer liver metastases and no previous
treatment of any systemic anti-swelling tumor treatment
4. No central nervous system metastases
5. No adjuvant therapy within 6 months prior to enrollment
6. ECOG PS: 0~1 points
7. Estimated survival ≥ 12 weeks
8. Normal function of major organs, meeting the following requirements (7 prior to
initiation of study treatment days): (1) Routine blood examination: (No blood
transfusion and no use of granules within 14 days before screening.) Cell
colony-stimulating factor [G-CSF], not corrected with medication):1) Hemoglobin
[HB]≥90g/L; 2) Absolute neutrophil count [ANC] ≥1.5×10 9 /L； 3) Platelets [PLT]
≥80×10 9 /L； (2) Blood biochemistry tests must meet the following criteria (no
transfusion in the 14 days before screening Protein): 1) Serum total bilirubin
[TBIL] ≤ 1.5 times the upper limit of normal (ULN); 2) Alanine aminotransferase
[ALT], aspartate aminotransferase [AST]<2.5×ULN ； If there is liver metastasis, ALT
and AST≤5×ULN； 3) Blood creatinine [Cr]≤1×ULN or endogenous creatinine clearance
rate > 50ml/min (Cockcroft-Gault formula); (3) International normalized ratio [INR]
≤ 2.3 or prothrombin time [PT] exceeding Over the range of normal controls≤6
seconds: (4) Urine protein < 2+ (if urine protein ≥ 2+, you can urinate eggs for 24
hours White quantitative, 24-hour urine protein quantification <1.0g can be
enrolled);
9. Women of childbearing potential must have a pregnancy test (serum or urine) within 7
days prior to enrollment The result is negative and voluntarily during the
observation period and after the last dose of study drug8 Use of appropriate methods
of contraception within a week; For males, it should be surgically sterile, or
Agrees to adopt appropriate during the observation period and for 8 weeks after the
last dose of study drug method contraception
10. Those who are expected to have good compliance can follow up the efficacy and
adverse reactions according to the requirements of the protocol.
Exclusion Criteria:
1. Other active malignancies within 5 years or concomitantly
2. Have uncontrolled cardiac clinical symptoms or diseases, such as: (1) in accordance
with: New York Heart Association (NYHA) criteria grade II or greater cardiac
insufficiency or Cardiac ultrasonography: LVEF (left ventricular ejection fraction)
<50%; (2) Instability Stereotyped angina; (3) Myocardial infarction within 1 year
prior to the start of study treatment Die; (4) Clinically significant
supraventricular or ventricular arrhythmias requiring treatment or intervention: (5)
QTc>450ms (male); QTc>470ms (Women) (The QTc interval is calculated by Fridericia's
formula; If the QTc is abnormal, interval can be used Approximately 2 minutes for
three consecutive tests, taking the average);
3. Those who have high blood pressure and cannot be reduced to the normal range by
antihypertensive drug treatment (admitted Systolic blood pressure ≥140mmHg or
diastolic blood pressure ≥90mmHg) (based on 2 measurements of ≥ The mean of the BP
readings obtained), which is allowed to be achieved through the use of
antihypertensive therapy above parameters
4. Coagulation abnormalities (INR>1.5×ULN, APTT>1.5×ULN), with: Bleeding tendency
5. Active bleeding
6. Uncontrolled active infection, chronic infectious disease, immunodeficiency syndrome
7. Subjects with known active hepatitis B (HBsAg positive and HBV DNA ≥10 3 copy number
or ≥1000 U/ml)
8. Presence of active autoimmune disease or history of autoimmune disease with possible
recurrence 9. Known history of severe allergy to the study drug
9. Uncontrolled infection at screening
10. Other patients who are considered by the treating physician to be unsuitable for
inclusion
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai General Hospital
Address:
City:
Shanghai
Zip:
200040
Country:
China
Status:
Recruiting
Contact:
Last name:
Jiang Long, MD
Phone:
+86 18017317460
Email:
jiang.long@shgh.cn
Investigator:
Last name:
Jiang Long, MD
Email:
Principal Investigator
Start date:
July 16, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Jiang Long
Agency class:
Other
Source:
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06531278
