Trial Title:
Phase Ib/II Clinical Study of Adebrelimab in Combination With Decitabine, Albumin-bound Paclitaxel, and Gemcitabine for the First-line Treatment of Metastatic Pancreatic Cancer
NCT ID:
NCT06454448
Condition:
Adebrelimab (SHR-1316)
Decitabine
Metastatic Pancreatic Cancer
Conditions: Official terms:
Pancreatic Neoplasms
Decitabine
Study type:
Interventional
Study phase:
Phase 1/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:
Adebrelimab;decitabine;
Description:
Adebrelimab:1200 mg Decitabine:10mg/m2 or 15mg/m2
Arm group label:
Study arm
Summary:
Pancreatic cancer is a kind of digestive system tumor with extremely high malignancy and
poor prognosis. Although the trend of benefit from immunotherapy in combination with
chemotherapy is currently reflected in several exploratory studies, the overall efficacy
is still relatively limited.
Dysregulation of epigenetic mechanisms, which is common in cancer, leads to
down-regulation of genes involved in tumor antigen processing or presentation, resulting
in immune evasion and thus affecting the efficacy of immunotherapy. Epigenetic inhibitors
may enhance the efficacy of immunotherapy by enhancing antigenicity and presentation of
tumor-associated antigens, reprogramming the tumor microenvironment to counteract
immunosuppression, and reversing cytotoxic T-cell depletion. Thus, decitabine-promoted
immunotherapeutic sensitization is a potential therapeutic avenue for mPDAC patients that
warrants further exploration in clinical trials. Taking into account the characteristics
of pancreatic cancer immunophenotype, exploring combination therapy regimens that enhance
anti-tumor immune response and improve the efficacy of immunotherapy has become an urgent
clinical problem.
This study is a prospective, single-arm, single-center, phase IB/II clinical study
exploring the efficacy and safety of adebrelimab in combination with decitabine,
albumin-bound paclitaxel, and gemcitabine in the first-line treatment of metastatic
pancreatic cancer. The primary study endpoints are DLT, RP2D and ORR. Secondary study
endpoints are OS, PFS, DCR, DoR and safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age 18-75 years old, male or female; 2. Histologically or cytologically confirmed
diagnosis of pancreatic cancer (originating from the pancreatic ductal epithelium),
with clinical records showing metastatic pancreatic cancer (stage IV according to
the AJCC 8th edition TNM staging of pancreatic cancer); 3. Have not received any
anti-tumor therapy (including chemotherapy, targeted, immunotherapy, etc.); 4. Must
have at least one measurable lesion as a target lesion (according to RECIST v1.1
criteria); the target lesion should not have received localized treatment such as
radiotherapy (lesions located within the area of previous radiotherapy may also be
selected as target lesions if progression is confirmed to have occurred and meets
RECIST1.1 criteria); 5. ECOG: 0 to 1; 6. Expected survival ≥ 3 months; 7. Good major
organ function, i.e., the following criteria are met (in the absence of receiving
any blood components, cell growth factors within 14 days prior to randomization):
1. Neutrophils ≥1.5*109/L; platelets ≥80*109/L; hemoglobin ≥9g/dl; serum albumin
≥3g/dl;
2. Total bilirubin ≤ 1.5 times the upper limit of normal value (biliary obstruction
allows biliary drainage); ALT and AST ≤ 3 times the upper limit of normal value (for
patients with hepatic metastases, it can be relaxed to ≤ 5 times the upper limit of
normal value);
3. Serum creatinine ≤1.5 times the upper limit of normal value, creatinine clearance
≥50ml/min;
4. INR ≤1.5 times the upper limit of normal value and APTT ≤1.5 times the upper limit
of normal value (for the use of a stable dose of anticoagulation therapy, such as
low molecular heparin or warfarin, and the INR is within the expected therapeutic
range of anticoagulants can be screened);
5. Electrocardiogram: QTcF ≤450ms (men), ≤470ms (women);
6. Cardiac ultrasound: LVEF (left ventricular ejection fraction) ≥50%; 8. Women of
childbearing potential must have had a negative blood pregnancy test within 3 days
prior to randomization and be willing to use an appropriate method of contraception
during the trial and for 6 months after completion of treatment. For men, this
should be surgical sterilization or agreement to use an appropriate method of
contraception for the duration of the study and for 3 months after completion of
treatment; 9. Subjects voluntarily enroll in this study by signing an informed
consent form.
Exclusion Criteria:
1. patients with pancreatic cancer originating from non-pancreatic ductal epithelium,
including pancreatic neuroendocrine carcinoma, pancreatic follicular cell carcinoma,
pancreatoblastoma, and solid-pseudopapillary tumors;
2. patients with known central nervous system metastases;
3. severe gastrointestinal dysfunction (with bleeding, obstruction; inflammation
greater than grade 2; diarrhea greater than grade 1);
4. the presence of third interstitial fluid (e.g., massive pleural fluid) that could
not be stabilized (without interventional therapy after drain removal) except for
ascites within 2 weeks before randomization;
5. Patients with clinically symptomatic ascites who require puncture or drainage or who
have received ascites drainage within the previous 3 months (except for imaging that
shows only a small amount of ascites that is manageable but not accompanied by
clinical symptoms);
6. current concomitant interstitial pneumonia or interstitial lung disease, or a prior
history of interstitial pneumonia or interstitial lung disease requiring hormonal
therapy, or other pulmonary fibrosis that may interfere with the determination and
management of immune-related pulmonary toxicity, mechanized pneumonia (e.g.,
occlusive bronchiectasis), pneumoconiosis, drug-associated pneumonitis, idiopathic
pneumonitis, or active pneumonia or severely impaired pulmonary function as
demonstrated by chest CT at the Screening Period Subjects; active tuberculosis;
7. the presence of active autoimmune disease or a history of autoimmune disease with
potential for relapse [including, but not limited to, autoimmune hepatitis,
interstitial pneumonitis, uveitis, enteritis, pituitary gland inflammation,
vasculitis, nephritis, hyperthyroidism, and hypothyroidism (subjects who can be
controlled by hormone replacement therapy only are eligible for enrollment)];
subjects who have a skin disease that does not require systemic treatment such as
vitiligo, psoriasis, alopecia that Controlled type I diabetes mellitus receiving
insulin therapy or asthma that has completely resolved in childhood and does not
require any intervention in adulthood may be enrolled;
8. known peripheral neuropathy (CTCAE ≥ grade 3);
9. a serious infection (CTCAE > grade 2) within 4 weeks prior to randomization, such as
severe pneumonia, bacteremia, or complications of infection requiring
hospitalization; signs and symptoms of infection requiring intravenous antibiotic
therapy (except for prophylactic use of antibiotics) within 2 weeks prior to
randomization;
10. received any of the following treatments: 1) Immunosuppressive or systemic hormone
therapy for immunosuppression within 2 weeks prior to randomization (dose >10 mg/day
prednisone or other equipotent hormone); 2) Radiation therapy within 2 weeks prior
to randomization; 3) Major surgery (e.g., open thoracic surgery, open abdominal
surgery, etc.) within 4 weeks prior to randomization; 4) Received any other clinical
study medication within 4 weeks prior to randomization, unless it was an
observational (non-interventional) clinical study or an interventional clinical
study follow-up.
11. abnormal coagulation, bleeding tendency or undergoing thrombolytic or anticoagulant
therapy. Prophylactic use of low-dose aspirin (≤100mg/day), low molecular heparin
(enoxaparin 40mg/day and other low molecular heparin at its equivalent dose) is
allowed;
12. patients with cardiac clinical conditions or diseases that are not well controlled,
such as (1) NYHA class 2 or higher heart failure, (2) unstable angina pectoris, (3)
myocardial infarction within 6 months, and (4) clinically significant
supraventricular or ventricular arrhythmias that require treatment or intervention;
13. malignancy other than pancreatic cancer within 5 years prior to randomization, with
the exception of adequately treated carcinoma in situ of the cervix, basal cell or
squamous epithelial cell carcinoma of the skin;
14. known hypersensitivity to PD-L1, albumin paclitaxel, gemcitabine, decitabine, and
any of the components of the above products;
15. known to have acquired immunodeficiency syndrome (AIDS) or HIV test positive, active
syphilis infection;
16. previous history of definite neurological or psychiatric disorders, including
epilepsy or dementia;
17. Subjects who, in the judgment of the investigator, have other factors that may cause
them to be forced to terminate the study midway, such as non-compliance with the
protocol, other serious illnesses (including psychiatric illnesses) that require
comorbid treatment, grossly abnormal values of clinically significant laboratory
tests, familial or social factors that may affect the safety of the subject or the
collection of trial data.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Tianjin Medical University Cancer Institute and Hospital
Address:
City:
Tianjin
Zip:
300052
Country:
China
Status:
Recruiting
Contact:
Last name:
Rui Liu
Phone:
13602139003
Email:
ruiliu688@126.com
Start date:
June 15, 2024
Completion date:
November 2026
Lead sponsor:
Agency:
Tianjin Medical University Cancer Institute and Hospital
Agency class:
Other
Source:
Tianjin Medical University Cancer Institute and Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06454448
