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Trial Title:
Neoadjuvant Anti-PD-1 Plus Chemotherapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma
NCT ID:
NCT05740995
Condition:
Esophageal Squamous Cell Carcinoma
Neoadjuvant Chemoimmunotherapy
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Conditions: Keywords:
Esophageal Squamous Cell Carcinoma
Neoadjuvant Chemoimmunotherapy
Study type:
Observational [Patient Registry]
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Drug
Intervention name:
neoadjuvant anti-PD-1 plus chemotherapy
Description:
Patients will be given preoperative treatment as below once recruited:
1. Chemotherapy is delivered and composed of two cycles of Nab-paclitaxel 135mg per
square meter of body-surface area and cisplatin 75mg per square meter of
body-surface area every 3 weeks;
2. PD-1 antibody is delivered 200 mg (iv, in 30 minutes) every 3 weeks;
3. After neoadjuvant therapy of 3-4 cycles, esophagectomy is performed. We advise
starting 4 cycles of identical chemoimmunotherapy in 6w after surgery.
Arm group label:
Neoadjuvant Anti-PD-1 Plus Chemotherapy Group
Summary:
The purpose of this study is to evaluate the outcomes and identify predictors of
neoadjuvant anti-PD-1 plus chemotherapy in locally advanced resectable esophageal
squamous cell carcinoma (ESCC). In this single-center cohort study, we are aiming to (1)
evaluate the therapeutic efficacy and survival benefits on patients with locally advanced
resectable ESCC (cT3-4aN0-1M0); (2) evaluate the value of genomic indicators including
MMR alternation status in predicting therapeutic responses and prognosis; (3) evaluate
the value of transcriptomic indicators including B cell lineage features in predicting
therapeutic responses and prognosis; (4) evaluate the value of microbial and metabolite
indicators in predicting therapeutic responses and prognosis. Whole exome sequencing, RNA
sequencing, 16S rRNA sequencing and Liquid Chromatography with tandem mass spectrometry
(LC-MS-MS) of samples of patients to neoadjuvant chemoimmunotherapy before and after
treatment are performed to explore the mechanisms of drug resistance and identification
of predictive and prognosis biomarkers.
Detailed description:
Multiple clinical trials investigated the safety and feasibility of neoadjuvant anti-PD-1
plus chemotherapy in esophageal squamous cell carcinoma (ESCC). However, the efficacy of
neoadjuvant chemoimmunotherapy was undetermined and existing biomarkers failed to provide
stable prediction of therapeutic responses. This study seek to further evaluate the
clinical outcomes and identify biological predictors of neoadjuvant anti-PD-1 plus
chemotherapy in locally advanced resectable esophageal squamous cell carcinoma (ESCC). In
this single-center cohort study, our aims include:
1. evaluate the therapeutic efficacy and survival benefits on patients with locally
advanced resectable ESCC (cT3-4aN0-1M0);
2. evaluate the value of genomic indicators in predicting therapeutic responses and
prognosis;
3. evaluate the value of transcriptomic indicators in predicting therapeutic responses
and prognosis;
4. evaluate the value of microbial and metabolite indicators in predicting therapeutic
responses and prognosis. Whole exome sequencing, RNA sequencing, 16S rRNA sequencing
and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) of samples of
responders and non-responders to neoadjuvant chemoimmunotherapy before and after
treatment are performed to explore the mechanisms of drug resistance and
identification of predictive and prognosis biomarkers, providing guidance to
clinical decisions.
Criteria for eligibility:
Study pop:
Patients with locally advanced resectable ESCC (cT3-4aN0-1M0)
Sampling method:
Probability Sample
Criteria:
Inclusion Criteria:
1. Histologically-confirmed squamous cell carcinoma of the esophagus;
2. Tumors of the esophagus are located in the thoracic cavity;
3. Pre-treatment stage as cT3-4aN0-1M0 (AJCC/UICC 7th Edition) (In case of stage cT4a,
curative resectability has to be explicitly verified by the local surgical
investigator prior to randomization).
4. Age is between 18 years and 75 years,
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
6. Adequate cardiac function. All patients should perform ECG, and those with a cardiac
history or ECG abnormality should perform echocardiography with the left ventricular
ejection fraction > 50 %;
7. Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in
pulmonary function tests;
8. Adequate bone marrow function (White Blood Cells >4x10^9 /L; Neutrophil >2.0×10^9
/L; Hemoglobin > 90 g/L; platelets>100x10^9 /L);
9. Adequate liver function (Total bilirubin <1.5x Upper Level of Normal (ULN);
Aspartate transaminase(AST) and Alanine transaminase (ALT)<1.5x ULN);
10. Adequate renal function (Glomerular filtration rate (CCr) >60 ml/min; serum
creatinine (SCr) ≤120 µmol/L);
11. The patient has provided written informed consent and is able to understand and
comply with the study;
Exclusion Criteria:
1. Patients with non-squamous cell carcinoma histology;
2. Patients with advanced inoperable or metastatic esophageal cancer;
3. Pre-treatment stage as cT1-2N0-1M0 (AJCC/UICC 7th Edition);
4. Pre-treatment stage as cN2-3 or cT4b(non-curatively-resectable verified by the local
surgical investigator, AJCC/UICC 7th Edition);
5. Patients with another previous or current malignant disease which is likely to
interfere with treatment or the assessment of response in the judgement of the local
surgical investigator.
6. Any patient with a significant medical condition which is thought unlikely to
tolerate the therapies. Such as cardiac disease (e.g. symptomatic coronary artery
disease or myocardial infarction within last 12 months), clinically-significant lung
disease, clinically-significant bone marrow, liver, renal function disorder;
7. Pregnant or lactating women and fertile women who will not be using contraception
during the trial;
8. Allergy to any drugs;
9. Participation in another intervention clinical trial with interference to the
therapeutic intervention during this study or during the last 30 days prior to
informed consent;
10. Expected lack of compliance with the protocol.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhongshan Hospital, Fudan University
Address:
City:
Shanghai
Zip:
200032
Country:
China
Status:
Recruiting
Contact:
Last name:
Di Ge, PhD
Email:
ge.di@zs-hospital.sh.cn
Contact backup:
Last name:
Jie Gu, PhD
Email:
gu.jie3@zs-hospital.sh.cn
Start date:
December 1, 2020
Completion date:
December 2028
Lead sponsor:
Agency:
Shanghai Zhongshan Hospital
Agency class:
Other
Source:
Shanghai Zhongshan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05740995
