Trial Title:
The Combination of Adebrelimab, Apatinib, and Lrinotecan Liposome for Second-line Treatment of Advanced Gastric Cancer
NCT ID:
NCT06592287
Condition:
Advanced Gastric Cancer
Conditions: Official terms:
Stomach Neoplasms
Apatinib
Conditions: Keywords:
Second line advanced gastric cancer
Lrinotecan liposome
Immune checkpoint inhibitors
Anti-L1 antibody
apatinib
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Adebrelimab + Apatinib + Lrinotecan liposome
Description:
Adebrelimab 1200 mg, iv. q3w
Apatinib 250 mg po qd
Lrinotecan liposome 80mg/m2, iv. q3w
Continue medication until disease progression, toxicity intolerance, initiation of new
anti-tumor treatment, withdrawal of knowledge, or continuous medication for at least 2
years.
Arm group label:
Frontline has received treatment with immune checkpoint inhibitors
Arm group label:
Previously not received immune checkpoint inhibitor treatment
Summary:
This study is a prospective, dual arm, open Ib/II phase clinical trial, with the main
objective of exploring the safety and efficacy of Adebrelimab combined with Apatinib and
Lrinotecan liposome for second-line treatment of advanced gastric cancer.
The study is divided into two stages. The first stage is the safety introduction period,
which includes 6 patients. Observe whether the subjects experience dose limiting toxicity
(DLT) during the observation period. If no subjects experience DLT during the observation
period, the study enters the next stage. The dose of Lrinotecan liposome used during the
safety introduction period is 80mg/m2, and the DLTs observation period is 1 cycle. If the
patient cannot tolerate it, the dose will be reduced to 60mg/m2.
In the second stage, advanced gastric cancer subjects who have progressed to first-line
treatment will be included in two cohorts: those who have previously received immune
checkpoint inhibitor therapy and have first-line PFS>7m (cohort 1) and those who
have received standard systemic chemotherapy (cohort 2). 30 subjects will be included in
each population, and a total of 66 subjects are planned to be enrolled.
The study includes a screening period (from the signing of the informed consent form by
the subjects to the first treatment, not exceeding 28 days), a treatment period
(Adebrelimab combined with Apatinib and Lrinotecan liposome), and a follow-up period
(including safety and survival follow-up).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age range: 18 to 75 years old, both male and female are acceptable;
2. Patients with gastric adenocarcinoma or gastroesophageal junction adenocarcinoma
diagnosed by histology or cytology;
3. Patients who have only received one failed systemic treatment for advanced diseases
in the past; After undergoing immunotherapy, the PFS of the treatment regimen
containing immune checkpoint inhibitors must be greater than 7 months;
4. According to the evaluation criteria for solid tumor efficacy 1.1 (RECIST v1.1),
there should be at least one measurable lesion that has not received local treatment
such as radiotherapy (lesions located within the previously irradiated area can also
be selected as target lesions if progression is confirmed);
5. ECOG score: 0-1 point;
6. Expected survival period ≥ 12 weeks;
7. The main organ functions well and the laboratory test data meets the following
standards: (1) Blood routine: absolute neutrophil count ≥ 1.5 × 109/L (or greater
than the lower limit of normal laboratory values in the research center), platelet
count ≥ 100 × 109/L, hemoglobin ≥ 90g/L; (2) Liver function: serum total bilirubin ≤
1.5 times the upper limit of the standard value (ULN), AST and ALT ≤ 2.5 times ULN.
If the patient has liver metastasis, this standard is ≤ 5 times ULN; (3) Renal
function: CrCl ≥ 60 ml/min/1.73 m2 (calculated according to the Cockcroft Gault
formula);
8. Female subjects with fertility, as well as male subjects with partners who are
fertility women, are required to use a medically approved contraceptive measure
(such as intrauterine devices, birth control pills, or condoms) during the study
treatment period, at least 6 months after the last use of Adebrelimab, at least 6
months after the last use of Apatinib, and at least 6 months after the last use of
chemotherapy;
9. HER2 negative;
10. Voluntarily join this study, sign informed consent form, have good compliance, and
cooperate with follow-up.
Exclusion Criteria:
1. History of gastrointestinal perforation and/or fistula within 6 months prior to the
first use of medication;
2. There is uncontrollable pleural effusion, pericardial effusion, or peritoneal
effusion that requires repeated drainage;
3. Have a history of allergies to any component of Adebrelimab in the past;
4. Have received any of the following treatments:
1. Received any other investigational drug within 4 weeks prior to the first use
of the investigational drug or had a half-life of no more than 5 from the last
investigational drug;
2. Simultaneously enrolled in another clinical study, unless it is an
observational (non interventional) clinical study or an interventional clinical
study follow-up;
3. Received anti-tumor therapy (including radiotherapy, chemotherapy,
immunotherapy, endocrine therapy, targeted therapy, biologic therapy, or tumor
embolization) within 2 weeks prior to the first use of the investigational
drug;
4. Subjects who need to receive corticosteroids (equivalent to>10mg prednisone
per day) within 2 weeks prior to the first use of the study drug. Allow the use
of hormones for routine chemotherapy pretreatment without the need for dose
adjustment. Other special circumstances require communication with the
researcher. In the absence of active autoimmune diseases, inhalation or local
use of steroids and corticosteroids with a dosage greater than 10mg/day of
prednisone efficacy dose are allowed as substitutes for adrenal cortex
hormones;
5. Individuals who have received anti-tumor vaccines or have received live
vaccines within 4 weeks prior to the first administration of the study drug;
6. Having undergone major surgery or suffered severe trauma within 4 weeks prior
to the first use of the investigational drug;
5. The toxicity of previous anti-tumor treatments has not recovered to ≤ CTCAE 5.0
Grade 1 (excluding hair loss) or the level specified in the inclusion/exclusion
criteria;
6. Patients with active central nervous system metastases;
7. Active autoimmune diseases, history of autoimmune diseases (such as interstitial
pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis,
hyperthyroidism, hypothyroidism, including but not limited to the above diseases or
syndromes); Excluding childhood asthma/allergies with vitiligo or those who have
already recovered, patients who do not require any intervention in adulthood;
Autoimmune mediated hypothyroidism treated with stable doses of thyroid replacement
hormone; Type I diabetes with a stable dose of insulin;
8. Have a history of immune deficiency, including HIV test positive, or have other
acquired or congenital immune deficiency diseases, or have a history of organ
transplantation and allogeneic bone marrow transplantation, or active hepatitis
(hepatitis B reference: HBV DNA test value exceeds 500 IU/ml or 2500 copies/mL);
9. The subject has uncontrolled cardiovascular clinical symptoms or diseases, including
but not limited to: (1) NYHA class II or above heart failure; (2) Unstable angina
pectoris; (3) Have experienced myocardial infarction within one year; (4) Clinically
significant supraventricular or ventricular arrhythmias that have not been
clinically intervened or are still poorly controlled after clinical intervention;
10. Within 4 weeks prior to the first use of the investigational drug, there has been a
severe infection (CTCAE 5.0>grade 2), such as severe pneumonia requiring
hospitalization, bacteremia, infection complications, etc; Baseline chest imaging
examination suggests the presence of active pulmonary inflammation, symptoms and
signs of infection within 2 weeks prior to the first use of the study drug, or the
need for oral or intravenous antibiotic treatment, except for prophylactic use of
antibiotics;
11. History of interstitial lung disease (excluding history of radiation pneumonia and
non infectious pneumonia that have not been treated with steroids);
12. Patients with active pulmonary tuberculosis infection found through medical history
or CT examination, or patients with a history of active pulmonary tuberculosis
infection within the past year before enrollment, or patients with a history of
active pulmonary tuberculosis infection more than one year ago but without formal
treatment;
13. Diagnosed with any other malignant tumor within 5 years prior to the first use of
the investigational drug, except for malignant tumors with low-risk metastasis and
mortality risk (5-year survival rate>90%), such as basal cell or squamous cell
carcinoma or cervical carcinoma in situ that have been adequately treated;
14. Pregnant or lactating women;
15. According to the researcher's assessment, there may be other factors that could
force the subject to terminate the study midway, such as having other serious
illnesses (including mental illnesses) that require concurrent treatment, severe
abnormal laboratory test values, family or social factors that may affect the
subject's safety or the collection of trial data.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
Address:
City:
Wuhan
Zip:
430030
Country:
China
Contact:
Last name:
Xianglin Yuan
Phone:
+8613986296106
Email:
yxl@medmail.com.cn
Start date:
September 30, 2024
Completion date:
September 30, 2026
Lead sponsor:
Agency:
Xianglin Yuan
Agency class:
Other
Source:
Huazhong University of Science and Technology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06592287
