Clinical trial NCT05740995: Neoadjuvant Anti-PD-1 Plus Chemotherapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma
Official title: A Single-center, Prospective Cohort Study of Neoadjuvant Anti-PD-1 Plus Chemotherapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Esophageal Squamous Cell Carcinoma
Neoadjuvant Chemoimmunotherapy
Keywords: Esophageal Squamous Cell Carcinoma
Neoadjuvant Chemoimmunotherapy
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2023-02-23
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with locally advanced resectable ESCC (cT3-4aN0-1M0)

Brief 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.

Eligibility 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.

Primary outcomes:
measure: Major pathological regression (MPR) rate
timeFrame: Up to the date of pathological reports obtained since the date of enrollment, up to 6 months
Secondary outcomes:
measure: Pathological response rate(pCR)
timeFrame: Up to the date of pathological reports obtained since the date of enrollment, up to 6 months
measure: objective response rate (ORR)
timeFrame: 36 months after the last subject participating in
measure: overall survival (OS)
timeFrame: 36 months after the last subject participating in
measure: Progression-free survival(PFS)
timeFrame: 36 months after the last subject participating in
measure: The correlation between detection of genomic, immune, microbial and metabolite features and the rate of therapeutic responses.
timeFrame: 36 months after the last subject participating in
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
Study officials:
affiliation: Fudan University
name: Di Ge, MD
role: STUDY_DIRECTOR
References: