TQB2450 Solution for Injection (TQB2450)+Paclitaxel+Cisplatin ± Anlotinib in the Treatment of Esophageal Cancer.

Esophageal Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05013697
• Other study ID #: TQB2450-II-13
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 2021
• Est. completion date: July 31, 2023

Study information

• Verified date: July 2021
• Source: Henan Cancer Hospital
• Contact: Suxia Luo, Doctor
• Phone: 0371-65587697
• Email: 2290773710[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: July 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Esophageal Neoplasms

Intervention

Drug:
• Paclitaxel + Cisplatin + TQB2450 injection+ Anlotinib
TQB2450 injection: 1200 mg, i.v.gtt , d1;Anlotinib 10mg, po.qd , d1-14;Paclitaxel 135mg/m2, i.v.gtt , d1; Cisplatin 60-75mg/m2, i.v.gtt , d1-d3; The above schemes are repeated every three weeks. After 4-6 cycles, the regimen is changed to Anlotinib (10mg, po.qd , d1-14)+TQB2450 injection(1200 mg, i.v.gtt , d1). The regimen is repeated every 3 weeks until the disease progresses.
• Paclitaxel + Cisplatin + TQB2450 injection
TQB2450 injection: 1200 mg, i.v.gtt , d1;Paclitaxel 135mg/m2, i.v.gtt , d1; Cisplatin 60-75mg/m2, i.v.gtt , d1-d3; The above schemes are repeated every three weeks. After 4-6 cycles, the regimen is changed to TQB2450 injection(1200 mg, i.v.gtt , d1). The regimen is repeated every 3 weeks until the disease progresses.

Locations

Country	Name	City	State
China	AnYang Tumor Hospital	Anyang	Henan
China	The People's Hospital Of AnYang City	Anyang	Henan
China	First Affiliated Hospital of Henan University of Science and Technolog	Luoyang	Henan
China	Henan Cancer Hospital	Zhengzhou	Henan
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Henan Cancer Hospital	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Country where clinical trial is conducted

China, 

References & Publications (8)

[1]He Jie, Shao Kang. The epidemiology, diagnosis and treatment of esophageal cancer in China and future strategies[J]. Chinese Journal of Cancer, 2011, 21(07): 501-504.

Blot, W. J. & Tarone, R. E. Esophageal cancer. Nat Rev Dis Prim. 3, 17048 (2017).

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epu — View Citation

Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C, Yang Z, Li H, Zou X, He J. Cancer incidence and mortality in China, 2014. Chin J Cancer Res. 2018 Feb;30(1):1-12. doi: 10.21147/j.issn.1000-9604.2018.01.01. — View Citation

Gandini S, Massi D, Mandalà M. PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2016 Apr;100:88-98. doi: 10.1016/j.critrevonc.2016.02.001. Epub 2016 Feb 10. Review. — View Citation

Guidelines Working Committee of Chinese Society of Clinical Oncology. Guidelines for Diagnosis and Treatment of Esophageal Cancer (2021 Edition) [M]. Beijing: People's Medical Publishing House, 2021.

Lu D, Ni Z, Liu X, Feng S, Dong X, Shi X, Zhai J, Mai S, Jiang J, Wang Z, Wu H, Cai K. Beyond T Cells: Understanding the Role of PD-1/PD-L1 in Tumor-Associated Macrophages. J Immunol Res. 2019 Nov 4;2019:1919082. doi: 10.1155/2019/1919082. eCollection 2019. Review. — View Citation

Ramjiawan RR, Griffioen AW, Duda DG. Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy? Angiogenesis. 2017 May;20(2):185-204. doi: 10.1007/s10456-017-9552-y. Epub 2017 Mar 30. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS, RECIST assessment)		each 42 days(Initial treatment) or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity (Up to 24 months)
Secondary	Progression-free survival (iPFS)		each 42 days(Initial treatment) or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity (Up to 24 months)
Secondary	Objective response rate (ORR)		each 42 days(Initial treatment) or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity (Up to 24 months)
Secondary	Disease control rate (DCR)		each 42 days(Initial treatment) or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity (Up to 24 months)
Secondary	Duration of response (DOR)		each 42 days(Initial treatment) or 63 days ( Maintenance treatment) up to Progressive Disease or Intolerable toxicity (Up to 24 months)
Secondary	Incidence of Treatment-related adverse Events		Through study completion, an average of 3 weeks