Clinical trial NCT06662110: IMmune Proteomics to Predict NeoAdjuvant Chemotherapy and ImmunoTherapy Response in Gastric Cancer
Official title: A Prospective Cohort Study on Serum Immune Protein Signature for Predicting Neoadjuvant Therapy Efficacy in Advanced Gastric Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Gastric Cancer, Gastroesophageal Junction Cancer
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2024-10-28
Enrollment: 206
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: Resectable gastric cancer patients who received neoadjuvant treatment followed by gastrectomy with D2 lymphadenectomy at Zhongshan Hospital, Fudan University

Brief summary: The overall efficacy of neoadjuvant treatment for advanced gastric cancer is limited due to significant heterogeneity in patient responses. While neoadjuvant therapy offers hope for improved clinical outcomes, the key challenge is accurately predicting individual treatment responses. Identifying reliable biomarkers to guide treatment decisions is therefore critical. Immune factors are pivotal in the efficacy of gastric cancer treatment, but most research has predominantly focused on the tumor immune microenvironment. This study aims to validate the predictive value of systemic immune markers in predicting neoadjuvant treatment responses in advanced gastric cancer.

Building on our previous research, where we established a retrospective cohort of patients with advanced gastric cancer undergoing preoperative chemotherapy, we employed a novel serum proteomics platform based on proximity extension assays (PEA) to measure key immune protein levels in patient serum. This led to the development of the PSRscore system, a serum immune protein score that effectively predicted tumor regression after preoperative chemotherapy (published in Cell Reports Medicine, doi: 10.1016/j.xcrm.2023.100931).

In this prospective cohort study, we will enroll 166 patients with resectable advanced gastric cancer undergoing neoadjuvant chemotherapy. Baseline serum samples will be collected prior to treatment, and the PSRscore will be used to predict tumor regression. Pathological evaluation post-chemotherapy will confirm tumor response, helping to further validate and refine the PSRscore system. Additionally, an exploratory cohort of 40 patients receiving combined neoadjuvant chemotherapy and immunotherapy will be included to evaluate the correlation between PSRscore and clinical benefit from immunotherapy.

This research is expected to lead to the development of a predictive diagnostic kit based on the PSRscore for advanced gastric cancer patients undergoing neoadjuvant therapy, with the ultimate goal of improving clinical decision-making and enhancing treatment outcomes for gastric cancer patients.


Eligibility criteria: Inclusion Criteria

1. Males or females aged 18 to 75 years;
2. Newly diagnosed histologically confirmed gastric adenocarcinoma;
3. Lesion located in the stomach or gastroesophageal junction as assessed by endoscopic ultrasound and enhanced CT, with clinical staging of T3-4NxM0 (based on the 8th edition of AJCC TNM classification);
4. Determined suitable for neoadjuvant chemotherapy or neoadjuvant chemotherapy combined with immunotherapy after multidisciplinary consultation, with potential for curative resection post-treatment. The chemotherapy regimen is restricted to fluoropyrimidine and platinum-based systemic chemotherapy; the immunotherapy regimen is restricted to immune checkpoint inhibitors.

Exclusion Criteria

1. Prior receipt of any anti-tumor therapy for current gastric cancer or receipt of anti-tumor drugs for other conditions within the past 4 weeks;
2. Presence of another malignancy or multiple primary tumors;
3. Serious comorbidities with a life expectancy of less than 5 years;
4. Severe chronic or active infections requiring systemic anti-infective therapy;
5. Blood transfusion within the past week;
6. Receipt of corticosteroid or immunosuppressive therapy within the past 2 weeks;
7. Administration of a live vaccine within the past 4 weeks.

Primary outcomes:
measure: the sensitivity and specificity of PSRscore in predicting tumor regression after neoadjuvant therapy in patients with advanced gastric cancer
timeFrame: From enrollment to the end of the pathological examination of all resected tumor samples, an average of 2 years
Secondary outcomes:
measure: the sensitivity and specificity of PSRscore in predicting objective response after neoadjuvant treatment in patients with advanced gastric cancer
timeFrame: From enrollment to the end of all the neo-adjuvant treatment, an average of 2 years
measure: the sensitivity and specificity of PSRscore in predicting progression-free survival (PFS) after neoadjuvant treatment in patients with advanced gastric cancer
timeFrame: though study completion, an average of 5 years
measure: the sensitivity and specificity of PSRscore in predicting overall survival (OS) after neoadjuvant treatment in patients with advanced gastric cancer
timeFrame: though study completion, an average of 5 years
Other outcomes:
Locations:
city: Xuhui District
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xuefei Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University
name: Zhaoqing Tang
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University
name: Yuan Gu
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tang Z, Gu Y, Shi Z, Min L, Zhang Z, Zhou P, Luo R, Wang Y, Cui Y, Sun Y, Wang X. Multiplex immune profiling reveals the role of serum immune proteomics in predicting response to preoperative chemotherapy of gastric cancer. Cell Rep Med. 2023 Feb 21;4(2):100931. doi: 10.1016/j.xcrm.2023.100931. Epub 2023 Jan 31.