Neoadjuvant Anti-PD-1 Plus Chemotherapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma

Sponsor
Shanghai Zhongshan Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05740995
Collaborator
(none)
40
59.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the outcomes and identify predicters 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: neoadjuvant anti-PD-1 (Keytruda) plus chemotherapy

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 predicters 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 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 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.

Study Design

Study Type:
Observational [Patient Registry]
Anticipated Enrollment :
40 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
A Single-center, Observational, Prospective Cohort Study of Neoadjuvant Anti-PD-1 Plus Chemotherapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma
Anticipated Study Start Date :
Mar 15, 2023
Anticipated Primary Completion Date :
Feb 15, 2025
Anticipated Study Completion Date :
Feb 15, 2028

Arms and Interventions

Arm Intervention/Treatment
Neoadjuvant Anti-PD-1 Plus Chemotherapy Group

Patients with locally advanced resectable ESCC (cT3-4aN0-1M0) who recieve neoadjuvant anti-PD-1 plus chemotherapy and donate biological samples

Drug: neoadjuvant anti-PD-1 (Keytruda) plus chemotherapy
Patients will be given preoperative treatment as below once recruited: 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; PD-1 antibody Keytruda is delivered 200 mg (iv, in 30 minutes) every 3 weeks; After neoadjuvant therapy of 3-4 cycles, esophagectomy is performed. We advise starting 4 cycles of identical chemoimmunotherapy in 6w after surgery.

Outcome Measures

Primary Outcome Measures

  1. Major pathological regression (MPR) rate [Up to the date of pathological reports obtained since the date of enrollment, up to 6 months]

    The resected specimen following neo-adjuvant treatment are assessed by using standardised work up of the resection specimen in the pathology department and standardised histological criteria for tumour regression grading. MPR was defined as ≤10% residual viable tumor.

Secondary Outcome Measures

  1. Pathological response rate(pCR) [Up to the date of pathological reports obtained since the date of enrollment, up to 6 months]

    The resected specimen following neo-adjuvant treatment are assessed by using standardised work up of the resection specimen in the pathology department and standardised histological criteria for tumour regression grading. PCR was defined as no evidence of vital residual tumor cells.

  2. objective response rate (ORR) [36 months after the last subject participating in]

    ORR is evaluated by chest, abdominal & pelvic CT/MRI based on RESIST 1.1. Evaluation will be conducted every 6 weeks during neoadjuvant therapy and every 6 months after surgery.

  3. overall survival (OS) [36 months after the last subject participating in]

    OS is defined as time interval from recruitment to all-caused death or censoring.

  4. Progression-free survival(PFS) [36 months after the last subject participating in]

    Disease recurrence is defined as locoregional (esophageal bed or anastomotic or regional lymph nodes) or metastatic (supraclavicular lymph nodes or distant organs).

  5. The correlation between detection of genomic, immune, microbial and metabolite features and the rate of therapeutic responses. [36 months after the last subject participating in]

    The detection of genomic, immune, microbial and metabolite features from biological samples before and after neoadjuvant chemoimmunotherapy is performed to anayze the correlation to treatment vulnerability.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 >4x109 /L; Neutrophil >2.0×109 /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 tonunderstand 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 chemotherapeutic or chemoradiotherapeutic intervention during this study or during the last 30 days prior to informed consent;

  10. Expected lack of compliance with the protocol.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Shanghai Zhongshan Hospital

Investigators

  • Study Director: Di Ge, MD, Fudan University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Shanghai Zhongshan Hospital
ClinicalTrials.gov Identifier:
NCT05740995
Other Study ID Numbers:
  • B2021-129
First Posted:
Feb 23, 2023
Last Update Posted:
Feb 23, 2023
Last Verified:
Feb 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Shanghai Zhongshan Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 23, 2023