Trial Title:
Clinical Trial to Evaluate the Safety and Effectiveness of TQB2618 Injection Combined Therapy in Patients With Advanced Esophageal Squamous Cell Carcinoma
NCT ID:
NCT05834543
Condition:
Advanced Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
TQB2618 injection, Penpulimab injection, Paclitaxel, Cisplatin
Description:
TQB2618 injection：Anti-TIM-3 monoclonal antibody. Penpulimab injection：Humanized
Monoclonal Antibody to Programmed Cell Death Protein 1 (PD-1).
Paclitaxel and Cisplatin are chemotherapy.
Arm group label:
TQB2618 injection +Penpulimab injection+Chemotherapy
Intervention type:
Drug
Intervention name:
Penpulimab injection, Paclitaxel, Cisplatin
Description:
Penpulimab injection：Humanized Monoclonal Antibody to Programmed Cell Death Protein 1
(PD-1).
Paclitaxel and Cisplatin are chemotherapy.
Arm group label:
Penpulimab injection+Chemotherapy
Intervention type:
Drug
Intervention name:
TQB2618 injection, Penpulimab injection, TQB3617capsules
Description:
TQB2618 injection：Anti-TIM-3 monoclonal antibody. Penpulimab injection：Humanized
Monoclonal Antibody to Programmed Cell Death Protein 1 (PD-1).
Arm group label:
TQB2618 injection +Penpulimab +TQB3617capsules
Summary:
To investigate the efficacy and safety of TQB2618 injection combined Penpulimab and
chemotherapy in the first-line treatment of recurrent/metastatic esophageal squamous cell
carcinoma compared with Penpulimab combined chemotherapy.
The primary efficacy outcomes are progression free survival (PFS) and objective response
rate (ORR).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Nonresectable locally advanced, recurrent or metastatic esophageal squamous cell
carcinoma (excluding mixed adenosquamous cell carcinoma) confirmed by histopathology
or cytology;
- For Cohort 1: Those who have not received systematic treatment, or have relapse at
least 6 months after the (new) adjuvant treatment/radical radiotherapy and
chemotherapy; For Cohort 2: received platinum-based chemotherapy and immuno
checkpoint inhibitor (PD-1/PD-L1, etc.) treatment and failed, the best effect of
front-line immunotherapy CR, PR, or SD lasted ≥ 24 weeks, and there was evidence of
imaging progression;
- Age: 18-75 years old (calculated based on the date of signing the informed consent);
Eastern Cooperative Oncology Group (ECOG) score: 0-1; The expected survival period
is more than 3 months;
- At least one measurable lesion was confirmed according to RECIST 1.1 standard;
Measurable lesions should not have received local treatment such as radiotherapy
(lesions located in the area of previous radiotherapy treated can also be selected
as target lesions if progression is confirmed);
- The main organs function well and meet the following standards:
1. The blood routine examination should meet the following requirements: (no blood
transfusion, no use of hematopoietic stimulator drugs for correction within 14
days before the examination)
1. Hemoglobin content (HB) ≥ 90g/L;
2. Absolute neutrophil count (ANC) ≥ 1.5 ×10^9/L；
3. Platelet count (PLT) ≥ 100 × 10^9/L.
2. Biochemical examination shall meet the following standards:
1. Total serum bilirubin (TBIL) ≤ 1.5 times of the upper limit of normal
value (ULN);
2. Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5ULN;
In case of liver metastasis, ALT and AST ≤ 5ULN;
3. Serum creatinine (Cr) ≤ 1.5ULN or creatinine clearance rate (CCr) ≥
60ml/min; (Cockcroft-Default formula);
3. Coagulation function is sufficient, defined as international normalized ratio
(INR) or prothrombin time (PT) ≤ 1.5 times ULN;
4. Thyroid function examination shall meet the following standards: thyroid
stimulating hormone (TSH) ≤ ULN; If abnormal, exam the level of T3 and T4,
patients with abnormal T3 and T4 can be enrolled.
5. Cardiac color doppler evaluation: left ventricular ejection fraction (LVEF) ≥
50%.
6. Female subjects of childbearing age should agree to use contraceptives (such as
intrauterine devices, contraceptives or condoms) during the study period and
within 6 months after the end of the study; The serum pregnancy test was
negative within 7 days before enrollment and must be a non-lactating subject;
Male subjects should agree to use contraception during the study period and
within 6 months after the end of the study.
7. Subjects volunteered to join the study and signed the informed consent form,
with good compliance;
Exclusion Criteria:
- Known esophageal squamous cell carcinoma which tended to complete obstruction under
endoscope and needed interventional treatment to relieve obstruction;
- Increased risk of bleeding or fistula caused by tumor significantly invading
adjacent organs (aorta or trachea);
- After esophageal or tracheal stent implantation;
- For Cohort 1: Patients who have used paclitaxel in adjuvant chemotherapy and have
relapse or metastasis within one year (note: those who have relapse or metastasis
for more than one year can be included in the study); Patients who received
cisplatin dose ≥ 300mg/m2 in the year before;
- The load of liver metastases accounts for more than 50% of the whole liver volume;
- For Cohort 1: Those who have received anti-PD-1 or anti-PD-L1/PD-L2, TIM-3, CTLA-4
drugs or other therapies that act on T-cell co-stimulation targets or checkpoints in
the past; For Cohort 2: Patients who have previously received BET inhibitor
treatment.
- Patients with any serious and/or uncontrollable diseases, including:
1. Have any clinical cardiovascular symptoms or diseases with poor control,
including but not limited to: patients with poor blood pressure control using
antihypertensive drugs (systolic blood pressure ≥ 150 mmHg or diastolic blood
pressure ≥ 100 mmHg); New York Heart Association (NYHA) grade II or above heart
failure; Unstable angina pectoris; Myocardial infarction occurred in the past
one year; Patients with arrhythmia (QTc ≥ 450ms (male), QTc ≥ 470ms (female)),
or patients with left ventricular ejection fraction (LVEF)<50% according to
cardiac color Doppler examination;
2. Active or uncontrolled serious infection (≥ NCI CTC AE level 2 infection);
3. Liver diseases such as cirrhosis, decompensated liver disease, chronic active
hepatitis (hepatitis B virus (HBV) reference: HBsAg positive, and HBV DNA
detected value exceeds the upper limit of normal value; hepatitis C virus (HCV)
reference: HCV antibody positive, and HCV virus titer detected value exceeds
the upper limit of normal value); Note: Subjects with positive hepatitis B
surface antigen or core antibody and hepatitis C patients who meet the
inclusion conditions need to receive continuous antiviral treatment to prevent
virus activation.
4. Poor control of diabetes (Fasting Blood Glucose (FBG)>10mmol/L);
5. Urine routine test showed that urine protein ≥++, and confirmed that the
24-hour urine protein content was more than 1.0 g;
6. Renal failure requiring hemodialysis or peritoneal dialysis;
7. Those who have epilepsy and need treatment;
- Major surgery (craniotomy, thoracotomy or laparotomy) has been performed within 4
weeks before the first dose of the study or is expected to require major surgery
during the study treatment.
- A history of gastrointestinal perforation and/or fistula within 6 months before
treatment; Or have experienced arterial/venous thrombosis events, such as
cerebrovascular accident (including transient ischemic attack), deep venous
thrombosis and pulmonary embolism;
- Known central nervous system metastasis and/or cancerous meningitis;
- Ascites with clinical significance, including any ascites that can be found in
physical examination. For ascites that have been treated in the past or still need
to be treated at present, subjected can be included if only a small amount of
ascites is shown by imaging and without symptoms;
- Patients with equal amount of effusion in both sides of the chest, or a large amount
of effusion in one side of the chest, or who have caused respiratory dysfunction and
need drainage;
- Wounds or fractures that have not been cured for a long time;
- Esophageal squamous cell carcinoma patients with active bleeding of the primary
lesion within 2 months; Pulmonary hemorrhage with NCI CTC AE grade>1 occurred within
4 weeks before enrollment; Bleeding at other sites with NCI CTC AE grade>2 occurred
within 4 weeks before enrollment; Patients with bleeding tendency (such as active
gastrointestinal ulcer) or undergoing thrombolytic or anticoagulant therapy such as
warfarin, heparin or its analogues;
- There is active pulmonary tuberculosis, or there is a history of active tuberculosis
infection within one year before enrollment, or there is a history of active
tuberculosis infection more than one year before enrollment, but they have not
received treatment;
- Interstitial lung disease requiring steroid hormone treatment;
- Uncontrolled metabolic disorder or other non-malignant tumor organ or systemic
disease or cancer secondary reaction, which may lead to higher medical risk and/or
uncertainty of survival evaluation;
- Patients with significant malnutrition (such as the need for continuous parenteral
nutrition ≥ 7 days), patients with Body Mass Index（BMI）<18.5kg/m2 or weight loss ≥
10% in the two months before screening.
- Those who have a history of abuse of psychotropic substances and are unable to quit
or have mental disorders;
- Have a history of immunodeficiency, including HIV positive or other acquired or
congenital immunodeficiency diseases, or have a history of organ transplantation and
hematopoietic stem cell transplantation;
- History of other primary malignant tumors, except for the following: 1) Malignant
tumors completely relieved for at least 2 years before enrollment and no other
treatment is required during the study period; 2) Nonmelanoma skin cancer or
malignant freckle-like nevus with sufficient treatment and no evidence of disease
recurrence; 3) Carcinoma in situ with sufficient treatment and no evidence of
disease recurrence;
- Those who are allergic to the study drug or its excipients, or to similar drugs;
- Pregnant or lactating female patients;
- There is an unrelieved toxic reaction higher than NCI CTC AE level 1 caused by any
previous treatment before the first medication, excluding hair loss;
- Active autoimmune diseases requiring systemic treatment (such as the use of disease
relief drugs, corticosteroids or immunosuppressants) have occurred within 2 years
before the first medication. Replacement therapy (such as thyroxine, insulin or
physiological corticosteroids for adrenal or pituitary insufficiency) is not
considered as systemic treatment;
- Have received systemic glucocorticoid therapy (dose>10mg/day prednisone or other
effective hormones) or any other form of immunosuppressive therapy within 2 weeks
before the start of the study;
- The history of live attenuated vaccine inoculation within 28 days before the first
administration or the planned live attenuated vaccine inoculation during the study
period;
- Have received chemotherapy, radiotherapy or other anti-tumor treatment within 4
weeks before the first medication (washout period is calculated from the end of the
last treatment); Note: Those who have received local radiotherapy in the past can be
enrolled if the following conditions are met: the end of radiotherapy is more than 3
weeks from the beginning of study treatment (brain radiotherapy is more than 2
weeks); And the target focus selected in this study is not in the radiotherapy area;
Or the target lesion is located in the radiotherapy area, but progress has been
confirmed.
- Participated in clinical trials of other anti-tumor drugs within 4 weeks before the
first medication (the washout period is calculated from the end of the last
treatment);
- Within 2 weeks before the first use of drug, the subjects have received the
treatment of traditional Chinese medicines (including compound cantharides capsule,
Kangai injection, Kanglaite capsule/injection, Aidi injection, Brucea javanica oil
injection/capsule, Xiaoaiping tablet/injection, cinobufagin capsule, etc.) with
anti-tumor indications specified in the drug labelling approved by National Medical
Products Administration (NMPA).
- Subjects who, according to the judgment of the investigator, have serious
concomitant diseases that endanger the safety of the patient or affect the
completion of the study, or who are considered that are not suitable for enrollment
due to other reasons .
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Tongling People's Hospital
Address:
City:
Tongling
Zip:
244099
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xianru Zhang, Master
Phone:
+86 13955936886
Email:
1015565142@qq.com
Facility:
Name:
The First Affiliated Hospital of Wannan Medical College
Address:
City:
Wuhu
Zip:
241000
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yiping Zhu, Doctor
Phone:
+86 13965197031
Email:
zhuyiping@wnmc.edu.cn
Contact backup:
Last name:
Jie Shen, Doctor
Phone:
+86 15922318586
Email:
Jie_shen23@aliyun.com
Facility:
Name:
AnYang Tumor Hospital
Address:
City:
Anyang
Zip:
455000
Country:
China
Status:
Recruiting
Contact:
Last name:
Jin Xia, Master
Phone:
+86 15890750990
Email:
15890750990@126.com
Facility:
Name:
The First Affiliated Hospital of Henan University of Science and Technology
Address:
City:
Luoyang
Zip:
471003
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhiye Zhang, Master
Phone:
+86 13783100985
Email:
13783100985@163.com
Facility:
Name:
The First Affiliated Hospital of Zhengzhou University
Address:
City:
Zhengzhou
Zip:
450000
Country:
China
Status:
Recruiting
Contact:
Last name:
Feng Wang
Phone:
+86 13938244776
Email:
fengw010@163.com
Facility:
Name:
Zhumadian Central Hospital
Address:
City:
Zhumadian
Zip:
463003
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yunfang Chen, Bachelor
Phone:
+86 13783961672
Facility:
Name:
Affiliated Hospital of Jining Medical College
Address:
City:
Jining
Zip:
272007
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Junye Wang, Bachelor
Phone:
+86 18678766866
Email:
jiningwangjunye@163.com
Facility:
Name:
Changzhi People's Hospital
Address:
City:
Changzhi
Zip:
046000
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jun Zhao, Doctor
Phone:
+86 13835578500
Email:
zhaojun380@163.com
Facility:
Name:
Heping Hospital Affiliated to Changzhi Medical College
Address:
City:
Changzhi
Zip:
046000
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Junyan Yu, Doctor
Phone:
+86 13720958692
Email:
hanbing398@163.com
Facility:
Name:
Jincheng General Hospital
Address:
City:
Jincheng
Zip:
048000
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yunxia Wang, Master
Phone:
+86 13593303335
Email:
16081363@qq.om
Start date:
May 26, 2023
Completion date:
December 2024
Lead sponsor:
Agency:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Agency class:
Industry
Source:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05834543
