NICCE: 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 Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Neoadjuvant Immunotherapy (PD-1 / PD-L1) Combined With Chemotherapy
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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.
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Outcome Measures
Primary Outcome Measures
- Pathologic Complete Response [2-5 years]
According to the detection of pathological specimens after operation, no malignant tumor cells were detected, so the patient achieved complete pathological remission.
Secondary Outcome Measures
- Disease-free Survival [2-5 years]
The patient achieved CR (complete remission) and still had no probability of recurrence after treatment in 2-years.
- Progression-Free-Survival [2-5 years]
The time between the beginning of treatment and the observation of disease progression or death from any cause.
- Overall survival [2-5 years]
The time from randomization to death from any cause.
- Security [2-5 years]
The safety of drugs was evaluated from four aspects: adverse events, adverse reactions, serious adverse events and serious adverse reactions.
- Objective Response Rate [2-5 years]
The proportion of patients whose tumor volume reduced to a predetermined value and could maintain the minimum time limit.
Other Outcome Measures
- Tumor markers [2-5 years]
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.
- Intestinal flora [2-5 years]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 18-70 Years old，
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The clinical stage of esophageal cancer confirmed by pathology was cT（1-3）N（1-3）M0
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No previous chemoradiotherapy
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ECOG PS: 0-1 points
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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.
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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.
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The patients voluntarily joined the study and signed the informed consent form. They had good compliance and cooperated with the follow-up.
Exclusion Criteria:
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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).
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Those who have used other drugs in clinical trials within 4 weeks before the first medication.
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Severe allergic reaction to monoclonal antibody.
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The number of neutrophils in peripheral blood was less than 1500 / mm3.
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There are cardiac clinical symptoms or diseases that are not well controlled.
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Previously received radiotherapy, chemotherapy, hormone therapy, surgery or molecular targeted therapy.
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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.
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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.
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The researchers judged the patients with high risk of esophageal perforation or no potential possibility of surgery through endoscopic ultrasonography or imaging.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tongji hospital | Wuhan | Hubei Provience | China | 430030 |
Sponsors and Collaborators
- Tongji Hospital
- National Natural Science Foundation of China
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- TJ-IRB20210624