Neoadjuvant Immunotherapy (PD-1 / PD-L1) Combined With Chemotherapy for Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma: a Single Center, Prospective, Open, One Arm Exploratory Clinical Study

Esophageal Squamous Cell Carcinoma Clinical Trial

— NICCE  

Official title:

Neoadjuvant Immunotherapy (PD-1 / PD-L1) Combined With Chemotherapy for Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma: a Single Center, Prospective, Open, One Arm Exploratory Clinical Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05028231
• Other study ID #: TJ-IRB20210624
• Status: Recruiting
• Start date: June 5, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: August 2021
• Source: Tongji Hospital
• Contact: Ni Zhang, Doctor
• Phone: +8613006315393
• Email: zhangnidoc[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To purpose of this study is to access the safety and efficacy of neoadjuvant Immunotherapy (PD-1 / PD-L1) combined with chemotherapy for locally advanced thoracic esophageal squamous cellcarcinoma.

Description:

Each patient will complete 2 cycles of neoadjuvant therapy and decide whether to operate after evaluating the curative effect if there is no active withdrawal of the subject from the trial or the researcher believes that the subject is not suitable for further trials. The patients after operation and without operation enter the survival follow-up period. If the imaging evaluation is PD after neoadjuvant therapy, the follow-up treatment shall be carried out according to the following principles: the imaging evaluation belongs to the continuous operation that can be operated; If the imaging evaluation was inoperable, radical concurrent radiotherapy and chemotherapy were performed. Postoperative adjuvant therapy shall be performed according to NCCN guidelines. If it is necessary to improve the local control rate, postoperative adjuvant radiotherapy is feasible. At the same time, imaging evaluation was performed until tumor recurrence and metastasis. After tumor recurrence and metastasis, all patients should also enter survival follow-up; In case of drug withdrawal (such as intolerable toxicity) other than recurrence and metastasis during treatment, the treatment is completed, the post-treatment visit is entered, and the survival follow-up is entered after recurrence.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age 18-70 Years old,

• The clinical stage of esophageal cancer confirmed by pathology was cT(1-3)N(1-3)M0

• No previous chemoradiotherapy

• ECOG PS: 0-1 points

• The functions of important organs meet the following requirements (excluding the use of any blood components and cell growth factors during the screening period):Absolute neutrophil count = 1.5 × 109/L; Platelet = 90 × 109/L; Hemoglobin = 9g / dl; Serum albumin = 3G / dl; Thyroid stimulating hormone (TSH) = ULN (if abnormal, the levels of T3 and T4 should be investigated at the same time. If the levels of T3 and T4 are normal, they can be included in the group); Bilirubin = ULN; ALT and AST = 1.5 times ULN; AKP = 2.5 times ULN; Serum creatinine = 1.5 times ULN or creatinine clearance = 60ml / min.

• Women of childbearing age must have taken reliable contraceptive measures or conducted pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative, and are willing to use appropriate contraceptive methods during the test and 8 weeks after the last administration of test drugs. For men, they must agree to use appropriate methods of contraception or surgical sterilization during the trial and 8 weeks after the last administration of the trial drug.

• The patients voluntarily joined the study and signed the informed consent form. They had good compliance and cooperated with the follow-up.

Exclusion Criteria:

• Any active autoimmune disease or history of autoimmunity (as follows, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism and hypothyroidism; Subjects with vitiligo or asthma in childhood have been completely relieved and do not need any intervention after adulthood can be included; Asthma in which subjects need bronchodilators for medical intervention cannot be included).

• Those who have used other drugs in clinical trials within 4 weeks before the first medication.

• Severe allergic reaction to monoclonal antibody.

• The number of neutrophils in peripheral blood was less than 1500 / mm3.

• There are cardiac clinical symptoms or diseases that are not well controlled.

• Previously received radiotherapy, chemotherapy, hormone therapy, surgery or molecular targeted therapy.

• The subjects were innate or acquired immunodeficiency (such as HIV), or active hepatitis (hepatitis B reference: HBsAg) positive, HBVDNA > 2000IU/ml or copy number > 104/ml; Hepatitis C reference: HCV antibody positive.

• According to the judgment of the researcher, the subject has other factors that may lead to the forced midway termination of this study, such as other serious diseases (including mental diseases) requiring combined treatment, serious laboratory abnormalities, accompanied by family or social factors, which will affect the safety of the subject, or the collection of data and samples.

• The researchers judged the patients with high risk of esophageal perforation or no potential possibility of surgery through endoscopic ultrasonography or imaging.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

Procedure:
• Neoadjuvant Immunotherapy (PD-1 / PD-L1) Combined With Chemotherapy
Each patient will complete 2 cycles of neoadjuvant therapy. After evaluating the curative effect, decide whether to operate or not. Patients with and without surgery enter the survival follow-up period.

Locations

Country	Name	City	State
China	Tongji hospital	Wuhan	Hubei Provience

Sponsors (2)

Lead Sponsor	Collaborator
Tongji Hospital	National Natural Science Foundation of China

Country where clinical trial is conducted

China, 

References & Publications (14)

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Chen K, Cheng G, Zhang F, Zhang N, Li D, Jin J, Wu J, Ying L, Mao W, Su D. Prognostic significance of programmed death-1 and programmed death-ligand 1 expression in patients with esophageal squamous cell carcinoma. Oncotarget. 2016 May 24;7(21):30772-80. doi: 10.18632/oncotarget.8956. — View Citation

Chen MF, Chen PT, Chen WC, Lu MS, Lin PY, Lee KD. The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression. Oncotarget. 2016 Feb 16;7(7):7913-24. doi: 10.18632/oncotarget.6861. — View Citation

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25. — View Citation

Huang J, Xu B, Mo H, Zhang W, Chen X, Wu D, Qu D, Wang X, Lan B, Yang B, Wang P, Zhang H, Yang Q, Jiao Y. Safety, Activity, and Biomarkers of SHR-1210, an Anti-PD-1 Antibody, for Patients with Advanced Esophageal Carcinoma. Clin Cancer Res. 2018 Mar 15;24 — View Citation

Lee JL, Park SI, Kim SB, Jung HY, Lee GH, Kim JH, Song HY, Cho KJ, Kim WK, Lee JS, Kim SH, Min YI. A single institutional phase III trial of preoperative chemotherapy with hyperfractionation radiotherapy plus surgery versus surgery alone for resectable es — View Citation

Lim SH, Hong M, Ahn S, Choi YL, Kim KM, Oh D, Ahn YC, Jung SH, Ahn MJ, Park K, Zo JI, Shim YM, Sun JM. Changes in tumour expression of programmed death-ligand 1 after neoadjuvant concurrent chemoradiotherapy in patients with squamous oesophageal cancer. E — View Citation

Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet. 2013 Feb 2;381(9864):400-12. doi: 10.1016/S0140-6736(12)60643-6. Review. — View Citation

Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul — View Citation

Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V; Australasian Gastro-Intestinal Trials Group. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. — View Citation

Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: — View Citation

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Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462-7. Erratum in: N Engl J Med 1999 Jul 29;341(5):384. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tumor markers	Tumor markers refer to those characteristic bioactive substances that can be detected that can reflect the development stage of malignant tumor cells. In a narrow sense, tumor markers refer to bioactive substances synthesized, secreted and released into blood and / or body fluid by malignant tumor cells, including enzymes, hormones, proteins, metabolites and other substances, Their occurrence and changes are closely related to the growth, diffusion, occurrence and development of malignant tumors.	2-5 years
Other	Intestinal flora	Intestinal flora homeostasis is called the organ of human body. Intestinal flora homeostasis plays an important role in the life activities of the body. It has important physiological significance in promoting the digestion and absorption of host nutrients, maintaining the normal physiological function of intestine, regulating body immunity and antagonizing the colonization of pathogenic microorganisms.	2-5 years
Primary	Pathologic Complete Response	According to the detection of pathological specimens after operation, no malignant tumor cells were detected, so the patient achieved complete pathological remission.	2-5 years
Secondary	Disease-free Survival	The patient achieved CR (complete remission) and still had no probability of recurrence after treatment in 2-years.	2-5 years
Secondary	Progression-Free-Survival	The time between the beginning of treatment and the observation of disease progression or death from any cause.	2-5 years
Secondary	Overall survival	The time from randomization to death from any cause.	2-5 years
Secondary	Security	The safety of drugs was evaluated from four aspects: adverse events, adverse reactions, serious adverse events and serious adverse reactions.	2-5 years
Secondary	Objective Response Rate	The proportion of patients whose tumor volume reduced to a predetermined value and could maintain the minimum time limit.	2-5 years