Trial Title:
Adebrelimab and a TKI in Combination With GEMOX in First-line Treatment of Advanced Biliary Tract Cancers (BTC)
NCT ID:
NCT06320301
Condition:
Biliary Tract Cancer
Gemox Chemotherapy
Conditions: Official terms:
Biliary Tract Neoplasms
Gemcitabine
Oxaliplatin
Tyrosine Kinase Inhibitors
Conditions: Keywords:
Biliary tract cancer
GEMOX
PD-L1
Adebrelimab
TKI
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:
Adebrelimab + GEMOX + TKI
Description:
Adebrelimab 20 mg/kg, once every 3 weeks (Q3W), maintained for 1 year. The interval
between two doses should not be less than 12 days.
Tyrosine kinase inhibitor (TKI) Lenvatinib: 12 mg (3 capsules 4 mg) or 8 mg (2 capsules 4
mg) once daily (QD) at fixed times daily, on an empty stomach or with food; Apatinib:
250mg orally, QD, 5 days of medication, 2 days off (5 on 2 off) or once every other day
(QOD), half an hour after meals; Sorafenib: 0.4g (2 × 0.2g) twice or once daily on an
empty stomach or with a low-fat or medium-fat diet Anlotinib: 12 mg orally before
breakfast, QD. The drug was taken continuously for 2 weeks and stopped for 1 week.
GEMOX: gemcitabine 800mg/m2 and oxaliplatin 85mg/m2, intravenous infusion, D2, D15, D29,
until 6 cycles of treatment were completed, or the patients who did not reach 6 cycles
had intolerable adverse reactions, then the combination chemotherapy was terminated.
Arm group label:
Adebrelimab + GEMOX + TKI
Other name:
Adebrelimab+ tyrosine kinase inhibitor (TKI) + gemcitabine - oxaliplatin (GEMOX)
Summary:
Patients with advanced biliary tract malignant tumors who had not received systematic
treatment before and could not be cured were selected as the subjects of the study. The
primary endpoint of the study was investigator-assessed 6-month progression-free survival
(6-month PFS%) based on the RECIST v1.1 criteria, and 43 subjects were planned to be
enrolled. Patients eligible for enrollment will receive Adebrelimab and a tyrosine kinase
inhibitor (TKI) in combination with gemcitabine and oxaliplatin (GEMOX).
Detailed description:
This is an open-label, single-arm clinical study to observe and evaluate the efficacy and
safety of Adebrelimab (PD-L1) and tyrosine kinase inhibitor (TKI) combined with
gemcitabine and oxaliplatin (GEMOX) in the first-line treatment of patients with advanced
biliary tract malignancies.
Subjects will be screened to receive Adebrelimab and TKI in combination with Gemcitabine
and Oxaliplatin (GEMOX) after they are fully informed and sign the informed consent.
Study treatment will continue until the subject develops intolerable toxicity, withdraws
informed consent, and progresses as determined by the investigator in accordance with
RECIST v1.1 (when the subject develops disease progression as defined in RECIST v1.1, if
the investigator assesses that the subject continues to have clinical benefit and can
tolerate the study treatment, The subject may continue treatment with the study drug;
treatment may be terminated if the subject is no longer considered to have a clinical
benefit), or other termination criteria specified in the protocol, whichever occurs
first.
After the subjects were enrolled in the study, the safety visit will be conducted in D1
of each treatment cycle, and the safety visit and survival follow-up will be continued
after the treatment.
Tumor imaging evaluation Imaging examination was performed every 6 weeks after enrollment
to evaluate the efficacy. Additional imaging studies and evaluations may be performed at
any time during the study if clinically indicated. Imaging evaluation of the tumor will
continue until disease progression is confirmed by the investigator according to the
RECIST v1.1 criteria or treatment is discontinued, whichever occurs later. Subjects who
ended treatment for reasons other than investigator-confirmed disease progression (per
RECIST v1.1) will also continue to be followed up at regular intervals for tumor imaging
evaluation after the end of treatment.
If the subject withdraws the knowledge, has started other anti-tumor treatment (except
Chinese patent medicine) or dies before the disease progression or termination of
treatment confirmed by the investigator according to RECIST1.1 criteria, there is no need
to continue the imaging evaluation. If the subject fails to meet the above termination
criteria for imaging evaluation, the tumor efficacy evaluation of other efficacy
evaluation criteria (RECIST v1.1, imRECIST) still needs to be continued even if the
disease progression of a certain efficacy evaluation criteria occurs.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1) The patient voluntarily participated in the study and signed the informed
consent;
-
2) ≥ 18 years old (calculated on the day of signing the informed consent), male or
female;
-
3) Patients with advanced biliary tract malignant tumors confirmed by
histopathology or cytology;
-
4) Subjects must be able to provide fresh or archived tumor tissue
(formalin-fixed, paraffin-embedded [FFPE] blocks or at least 5 unstained FFPE
slides) and their pathology reports. If less than 5 unstained slides are
available from the subject or tumor tissue is not available (e.g., because of
exhaustion of previous diagnostic tests), enrollment may be allowed on a
case-by-case basis after discussion;
-
5) The subject is not suitable for surgery, or has progressed after surgery and/or
local treatment;
-
6) Patients with progression after local therapy, where local therapy (including
but not limited to surgery, radiotherapy, arterial embolization, arterial
infusion, radiofrequency ablation, cryoablation, or percutaneous ethanol
injection) has been completed at least 4 weeks prior to the baseline imaging
scan, Toxicity (except alopecia) caused by topical treatment must be restored
to the National Cancer Institute-Common Terminology Criteria for Adverse
Events, Version 5.0 (NCI-CTCAE v5.0) rating ≤ 1;
-
7) No previous systemic therapy for BTC
-
8) At least one measurable lesion (according to the requirements of RECIST v1.1,
the long diameter of the measurable lesion on spiral CT scan is ≥ 10 mm or the
short diameter of the enlarged lymph node is ≥ 15 mm; the lesion that has
received local treatment in the past can be used as the target lesion after the
progress is confirmed according to the criteria of RECIST v1.1)
-
9) The physical condition score of the Eastern Cooperative Oncology Group (ECOG)
was 0 ~ 2 (see Attachment 1 for the ECOG score standard);
-
10) Expected survival ≥ 12 weeks;
-
11) The functions of main organs are basically normal, and there are serious
abnormalities of blood, heart, lung, liver, kidney, bone marrow and other
functions and immunodeficiency diseases, which meet the requirements of the
protocol: A) Blood routine examination: (except for hemoglobin, no blood
transfusion within 14 days before screening, no use of granulocyte
colony-stimulating factor [G-CSF], and no use of corrective therapy within 7
days) I. Hemoglobin ≥ 90 G/L; II. Neutrophil count ≥ 1.5 × 109/L; III. Platelet
count ≥ 50 × 109/L; B) Biochemical examination: (no albumin transfusion within
14 days) I. Serum albumin ≥ 29 G/L; II. Alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN); III.
Total bilirubin (TBIL) ≤ 1.5 times ULN;
IV. Creatinine Cr ≤ 1.5 X ULN or Cr clearance > 50 mL/min (Cockcroft-Gault formula
below):
Male: Cr clearance = ( (140-age) × body weight)/ (72 × blood Cr) Female: Cr clearance = (
(140-age) × body weight)/ (72 × blood Cr) × 0.85 Weight unit: kg; Blood Cr unit: mg/mL;
V. Urine protein < 2 + (if urine protein ≥ 2 +, 24-hour (H) urine protein can be
quantified, and 24-hour urine protein < 1.0 G can be included in the group); C)
Coagulation function: activated partial thromboplastin time (APTT) and international
normalized ratio (INR) ≤ 1.5 × ULN (can be screened for the use of stable dose of
anticoagulant therapy such as low molecular weight heparin or warfarin and INR is within
the expected therapeutic range of anticoagulant); D) Thyroid-stimulating hormone (TSH) ≤
ULN; if abnormal, T3 and T4 levels should be examined, and if T3 and T4 levels are
normal, they can be included; Color Doppler echocardiography: left ventricular ejection
fraction (LVEF) was greater than or equal to 60%.
-
12) Fertile women: must agree to abstain from sex (abstain from heterosexual
intercourse) or use a reliable, effective method of contraception for at least
120 days from the signing of the informed consent until the final
administration of the study drug. Serum HCG test must be negative within 7 days
before the start of study treatment; And must be non-lactating. A woman is
considered fertile if she has menstruated, has not yet reached postmenopausal
status (no continuous periods for ≥12 months, no cause other than menopause is
found), and has not undergone sterilization (such as hysterectomy, bilateral
tubal ligation, or bilateral oophorectomy).
-
13) For male patients whose partner is a woman of reproductive age, they must agree
to abstain from sex for at least 120 days from the signing of the informed
consent until the final administration of the study drug, or to use a reliable
and effective method of contraception. Male subjects also had to agree not to
donate sperm during the same time period. Male subjects with a pregnant partner
are required to use condoms and do not need to use other methods of
contraception.
Exclusion Criteria:
-
1) Active malignancies other than BTC within 5 years or at the same time. Cured
localized tumors, such as skin basal cell carcinoma, skin squamous cell
carcinoma, superficial bladder carcinoma, prostate carcinoma in situ, cervical
carcinoma in situ, breast carcinoma in situ, etc., could be included in the
group.
-
2) Patients who are preparing for or have previously received organ or allogeneic
bone marrow transplantation;
-
3) Other investigational drug treatment received within 28 days prior to the start
of study treatment;
-
4) Moderate and severe ascites with clinical symptoms, i.e. requiring therapeutic
puncture, drainage or Child-Pugh score > 2 (except for those with only a small
amount of ascites on imaging but without clinical symptoms); uncontrolled or
moderate or more pleural effusion and pericardial effusion;
-
5) If there is a history of gastrointestinal bleeding or a definite tendency of
gastrointestinal bleeding within 6 months before the start of study treatment,
such as bleeding risk or severe esophageal and gastric varices, local active
gastrointestinal ulcer lesions, and persistent positive fecal occult blood,
they should not be included in the group (if the fecal occult blood is positive
at baseline, it can be reexamined, and if it is still positive after
reexamination, Gastroduodenal endoscopy (EGD) is required, and esophagogastric
varices with EGD suggesting a risk of bleeding are not eligible);
-
6) Abdominal fistula, gastrointestinal perforation, or abdominal abscess within 6
months prior to the start of study treatment;
-
7) Known presence of inherited or acquired bleeding (e.g., coagulopathy) or
thrombophilia, e.g., in patients with hemophilia; current or recent (within 10
days prior to the start of study treatment) use of full-dose oral or injectable
anticoagulants or thrombolytics for therapeutic purposes (low-dose aspirin,
low-molecular-weight heparin, prophylactic use permitted);
-
8) current or recent use (within 10 days prior to study treatment) of aspirin (>
325 mg/day (maximum antiplatelet dose) or dipyridamole, ticlopidine,
clopidogrel, and cilostazol;
-
9) Thrombotic or embolic events, such as cerebrovascular accident (including
transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary
embolism, etc., occurred within 6 months before the start of study treatment;
-
10) Clinical symptoms or diseases of the heart that are not well controlled, such
as:
1. LVEF (left ventricular ejection fraction) < 50% according to New York Heart
Association (NYHA) standard II or above cardiac dysfunction or cardiac color
Doppler ultrasound examination;
2. unstable angina pectoris;
3. Myocardial infarction within 1 year prior to the start of study treatment;
4. Supraventricular or ventricular arrhythmias of clinical significance require
treatment or intervention;
5. QTc > 450ms (male); QTc > 470ms (female) (QTc interval is calculated by
Fridericia formula; if QTc is abnormal, it can be detected three times at an
interval of 2 minutes, and the average value is taken);
- 11)Hypertension that is not well controlled by antihypertensive medication (systolic
blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg) (based on the
average of BP readings obtained from ≥ 2 measurements) allows the use of
antihypertensive therapy to achieve the above parameters; previous hypertensive
crisis or hypertensive encephalopathy;
-
12) Major vascular disease (e.g., aortic aneurysm requiring surgical repair or with
recent peripheral arterial thrombosis) within 6 months prior to the start of
study treatment; severe, unhealed or dehiscent wounds, and active ulcers or
untreated fractures; Major surgery has been performed within 4 weeks prior to
the start of study treatment (except for diagnosis) or is expected to be
performed during the study period;
-
13) There is evidence of intra-abdominal pneumatosis that cannot be explained by
puncture or recent surgery;
-
14) prior or present central nervous system metastasis; Metastatic disease
involving major Airways or vessels (for example, total occlusion of the main
portal vein or vena cava due to tumor invasion, where the main portal vein is
the confluence of the splenic vein and the superior mesenteric vein and where
the hepatic portal vein divides into left and right branches) or a large
mediastinal tumor mass located in the center (< 30 mm from the carina) should
be excluded from the group;
-
15) Patients with history of hepatic encephalopathy; Current interstitial pneumonia
or interstitial lung disease, or a previous history of interstitial pneumonia
or interstitial lung disease requiring hormone therapy, or other pulmonary
fibrosis, organizing pneumonia that may interfere with the judgment and
management of immune-related pulmonary toxicity (e. Bronchiolitis obliterans),
pneumoconiosis, drug-associated pneumonia, idiopathic pneumonia, or evidence of
active pneumonia on computed tomography (CT) images of the chest during the
screening period, or subjects with severely impaired lung function, with a
history of radiation pneumonitis in the permissive field; active tuberculosis;
-
16) Active autoimmune disease or history of autoimmune disease with potential for
recurrence (including but not limited to: autoimmune hepatitis, interstitial
pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis,
hyperthyroidism, hypothyroidism [only subjects that can be controlled by
hormone replacement therapy may be included]); Subjects with skin diseases that
do not require systemic treatment such as vitiligo, psoriasis, alopecia,
controlled type I diabetes mellitus on insulin therapy, or asthma that has
completely resolved in childhood and does not require any intervention in
adulthood may be included; asthma patients who require medical intervention
with bronchodilators may not be included;
-
17) use of immunosuppressant or systemic hormone therapy for immunosuppression
(dose > 10 mg/day prednisone or other iso-effective hormone) within 14 days
prior to initiation of study treatment;
-
18) Known history of severe allergy to any monoclonal antibody drug;
-
19) Severe infection within 4 weeks prior to the start of study treatment,
including but not limited to hospitalization for complications of infection,
bacteremia, or severe pneumonia; therapeutic antibiotics administered orally or
intravenously within 2 weeks prior to the start of study treatment (patients
receiving prophylactic antibiotics (e.g., to prevent urinary tract infection or
exacerbation of chronic obstructive pulmonary disease are eligible for the
study);
-
20) patients with congenital or acquired immune deficiency (such as HIV infection);
-
21) co-infection with hepatitis B and hepatitis C;
-
22) Have received live attenuated vaccine within 28 days prior to the start of
study treatment or are expected to require such vaccine during treatment with
or within 60 days of the last dose of Aderbelizumab In the judgment of the
investigator, the patient has other factors that may affect the results of the
study or lead to the forced termination of the study, such as alcoholism, drug
abuse, other serious diseases (including mental illness) requiring combined
treatment, serious laboratory abnormalities, accompanied by family or social
factors, which will affect the safety of the patient.
Gender:
All
Minimum age:
N/A
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Address:
City:
Guanzhou
Zip:
512000
Country:
China
Status:
Recruiting
Contact:
Last name:
Junkai Ren
Phone:
86-18664506517
Email:
rjk119234@163.com
Contact backup:
Last name:
Wenbin Li
Phone:
86-13602773101
Start date:
April 1, 2024
Completion date:
June 1, 2026
Lead sponsor:
Agency:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Agency class:
Other
Collaborator:
Agency:
Suzhou Suncadia Biopharmaceuticals Co., Ltd.
Agency class:
Industry
Source:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06320301