Clinical trial NCT05013697: TQB2450 Solution for Injection (TQB2450)+Paclitaxel+Cisplatin ± Anlotinib in the Treatment of Esophageal Cancer.
Official title: A Multicenter Exploratory Study of Paclitaxel+Cisplatin+TQB2450 Injection Combined With or Without Anlotinib in the First-line Treatment of Advanced Esophageal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Esophageal Neoplasms
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
First posted: 2021-08-19
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The regimen of paclitaxel+cisplatin+TQB2450 injection combined or not combined with anlotinib is the first-line treatment of advanced esophageal squamous cell carcinoma. Take PFS as the main evaluation index, the purpose is to evaluate its effectiveness and safety


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed squamous cell carcinoma of the esophagus, locally advanced, unresectable, recurrent or metastatic disease.
* Those who have not received systemic treatment before, or who relapsed after (new) adjuvant therapy/radical surgery more than 6 months ; Note: Including advanced or recurrent Patients who ever received only radiotherapy on non-target lesions. The duration from the end of palliative treatment for local lesions (non-target lesions) to enrollment should \> 2 weeks;
* According to RECIST 1.1, at least one measurable lesion; the measurable lesions should not have received local treatment such as radiotherapy (for the lesions in the area where received local radiotherapy, it can also be regarded as a target lesion if confirmed to progress according to the recist1.1);
* 18 and 75 years old;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1；Life expectancy of at least 3 months.
* the main organ function to meet the following criteria:

  (1)Blood routine tests met the following requirements:

  a) haemoglobin(HB)≥90g/L ； b) absolute neutrophil count(NEUT)≥1.5×109/L ； c) platelet count(PLT)≥100×109/L；

  （2） Biochemical tests met the following requirements： total bilirubin(TBIL)≤ 1.5 times the upper limit of normal (ULN) .≤5 × ULN if with liver involvement； serum creatinine ≤1.5 × the ULN or creatinine clearance≥50mL/min。

  （3） Coagulation or thyroid function meet the following criteria: International Normalized Ratio (INR) ≤1.5 and Partial Thromboplastin Time (PT) or activated PTT (APTT) ≤1.5 × (ULN))."
* Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of study
* The patient volunteers to participate in the study, signs a consent form, has good compliance, and obeys the follow-up, and is willing and able to follow the protocol during the study.

Exclusion Criteria:

* Patients tends to have complete obstruction or patients requiring interventional treatment for obstruction;
* Patients with a high risk of bleeding or perforation due to the apparent invasion of adjacent organs (aorta or trachea) of the esophageal lesion, or patients who have formed fistulas;
* Patients with symptoms of hematemesis, hematochezia and daily bleeding ≥ 2.5 mL, or any bleeding event with Common Terminology Criteria for Adverse Events （CTCAE） level 3 within 3 months before screening;
* allergic to study drugs 、paclitaxel and cisplatin preparations or excipients;
* Adjuvant chemotherapy patients who have used paclitaxel or cisplatin, and relapse or metastasize within one year
* A variety of factors affecting oral medications (such as inability to swallow, chronic diarrhea, and intestinal obstruction);
* patients with any severe and / or uncontrolled disease, including:Unsatisfactory blood pressure control using antihypertensive drugs (systolic blood pressure ≥150 mmhg or diastolic blood pressure ≥100) Mmhg) patients; patients with grade ≥ myocardial ischemia or myocardial infarction, arrhythmia (including qt interval ≥ 480ms); according to nyha criteria, iii-iv cardiac dysfunction, or cardiac ultrasonography prompted left ventricular ejection fraction (lvef) \<50% of patients;live Severe infection that is sexual or uncontrolled;Liver diseases such as cirrhosis, decompensated liver disease, chronic active hepatitis;poor diabetes control (fasting blood glucose (fbg)\>10mmol/l);Urine routine indicates that urine protein ≥ ++, and confirmed 24-hour urine protein quantitation \> 1.0 g
* long-term unhealed wounds or fractures;
* Patients with active hemorrhage within 2 months of primary lesions; pulmonary hemorrhage with NCI CTCAE grade \>1, 4 weeks before of enrollment; other sites of bleeding NCI CTCAE grade \>2, 4 weeks before of enrollment; patients with bleeding tendency (such as active gastrointestinal ulcers) or patients undergoing thrombolytic or anticoagulant therapy such as warfarin, heparin or its analogues;
* Have undergone major surgery (craniotomy, thoracotomy or open surgery) within 4 weeks prior to the first dose study or Major surgery is required during the study period.
* A history of gastrointestinal perforation and/or fistula occurred within 6 months prior to treatment; or an overactive/venous thrombosis event such as a cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, and lung Embolism；
* Symptomatic central nervous system metastasis and/or cancerous meningitis are known to exist;
* Clinically significant ascites, including any ascites that can be found on a physical examination, ascites that has been treated or currently in need of treatment, and only those with a small amount of ascites but no symptoms can be selected;
* A moderate amount of fluid in both sides of the chest, or a large amount of fluid in one side of the chest, or has caused respiratory dysfunction Patient to be drained;
* known to have active tuberculosis;
* suffering from interstitial lung disease requiring steroid therapy;
* Uncontrolled metabolic disorders or other non-malignant tumors or systemic diseases or cancer secondary reactions that can lead to higher medical risks and/or survival Evaluation of uncertainty;
* Significantly malnourished patients;
* those who have a history of psychotropic substance abuse and are unable to quit or have a mental disorder;
* A history of immunodeficiency, including a positive HIV test or other acquired, congenital immunodeficiency disease, or a history of organ transplantation;
* History of other primary malignancies, but the following : 1) complete remission of malignant tumors for at least 2 years prior to enrollment and no additional treatment during the study; 2) non-melanoma skin cancer or malignant freckle-like sputum with adequate treatment and no evidence of disease recurrence; 3) adequately treated and In situ carcinoma without evidence of disease recurrence;
* Female patients who are pregnant or breastfeeding;
* According to the judgment of the investigator, there is a concomitant disease that seriously endangers the safety of the patient or affects the completion of the study.

Primary outcomes:
measure: Progression free survival (PFS， RECIST assessment)
timeFrame: each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months）
Secondary outcomes:
measure: Progression-free survival (iPFS)
timeFrame: each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months）
measure: Objective response rate (ORR)
timeFrame: each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months）
measure: Disease control rate (DCR）
timeFrame: each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months）
measure: Duration of response (DOR)
timeFrame: each 42 days（Initial treatment） or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity （Up to 24 months）
measure: Incidence of Treatment-related adverse Events
timeFrame: Through study completion, an average of 3 weeks
Other outcomes:
Locations:
city: Anyang
country: China
facility: AnYang Tumor Hospital
state: Henan
city: Anyang
country: China
facility: The People's Hospital Of AnYang City
state: Henan
city: Luoyang
country: China
facility: First Affiliated Hospital of Henan University of Science and Technolog
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
Study officials:
affiliation: Henan Cancer Hospital
name: Suxia Luo, Doctor
role: STUDY_CHAIR
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