Clinical trial NCT05028231: 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
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Esophageal Squamous Cell Carcinoma
Neoadjuvant Therapies
Keywords: Immunotherapy
Chemotherapy
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
First posted: 2021-08-31
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: In this clinical trial, patients with resectable thoracic esophageal squamous cell carcinoma can receive neoadjuvant immunotherapy and neoadjuvant chemotherapy before operation.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pathologic Complete Response
timeFrame: 2-5 years
Secondary outcomes:
measure: Disease-free Survival
timeFrame: 2-5 years
measure: Progression-Free-Survival
timeFrame: 2-5 years
measure: Overall survival
timeFrame: 2-5 years
measure: Security
timeFrame: 2-5 years
measure: Objective Response Rate
timeFrame: 2-5 years
Other outcomes:
measure: Tumor markers
timeFrame: 2-5 years
measure: Intestinal flora
timeFrame: 2-5 years
Locations:
city: Wuhan
country: China
facility: Tongji hospital
state: Hubei Provience
Study officials:
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