Clinical trial NCT05661110: Biomarker Analysis of HIPEC Combined With PD1/PDL1 Inhibitor for Gastric Cancer With Peritoneal Metastasis
Official title: Integrated Biomarker Analysis for Hyperthermic Intraperitoneal Chemotherapy(HIPEC) Combined PD1/PDL1 Inhibitor Treatment in Patients of Advanced Gastric Cancer With Peritoneal Metastasis
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Gastric Cancer
Keywords: Biomarker
Lead sponsor: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2022-12-22
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Advanced gastric adenocarcinoma confirmed by histology with peritoneal metastasis

Brief summary: A single-center, observational study, integrated biomarker analysis of HIPEC combined Programmed cell death 1 /Programmed cell death 1 ligand 1(PD1/PDL1)inhibitor in previously treated patients of advanced gastric cancer with peritoneal metastasis. Tests will be performed on tumor tissue and blood samples, and imaging assessments will be reviewed in order to monitor how well each patient responds to treatment. This is an observational study, so participants will not receive cancer treatment, other than the treatment received as standard of care.

Detailed description: To analyze the correlation between genomic alterations, gene expression characteristics and the efficacy of HIPEC combined with PD1/PDL1 inhibitor conversion therapy in patients with peritoneal metastasis of gastric cancer. Circulating tumor DNA(ctDNA) in plasma samples and DNA, RNA in tumor tissue sample were obtained over the course of HIPEC combined PD1/PDL1 inhibitor conversion treatment will be assessed by high-intensity, next-generation sequencing(NGS) to identify genomic alterations. The assay will performed used AmoyDx® Master Panel(Amoy Diagnostics Co., Xiamen, China), which contains 559 genes for DNA mutation detection and 1813 genes for RNA expression and fusion detection. Data acquired will be analyzed to characterize the association between these genetic elements, clinical response, and durability of responses. There will be prospective groups for the study. Samples will be collected from patients in the prospective cohort who have been treated with HIPEC combined PD1/PDL1 inhibitor at Affiliated Cancer Hospital \& Institute of Guangzhou Medical University under standard of conversion treatment.

Eligibility criteria: Inclusion Criteria:

1. Advanced gastric (gastroesophageal junction) adenocarcinoma confirmed by histology;
2. Age 18-75 years, Male or Non-pregnant female
3. Eastern Cooperative Oncology Group(ECOG): 0\~1；
4. Negative for human epidermal growth factor receptor 2(HER-2) by immunocytochemistry or fluorescence in situ hybridization；
5. The presence of gastric cancer peritoneal metastasis is confirmed by laparoscopic exploration, and the PCI≤20；
6. Patients had received HIPEC combined with PD1/PDL1 inhibitor conversion therapy.
7. Signed the Informed Consent Form, and blood and tissue samples can be obtained;

Exclusion Criteria:

1. Other distal metastases besides peritoneal metastases (e.g., liver, lung, pleural, brain, bone metastases, etc.);
2. Other patients who were considered unsuitable for inclusion by the researchers;

Primary outcomes:
measure: Relationship between the status, numerical changes of ctDNA during HIPEC combined with PD1/PDL1 inhibitor conversion therapy and postoperative R0 resection rate.
timeFrame: 3 months
Secondary outcomes:
measure: Genomic changes of ctDNA and see if they are predictive of ORR.
timeFrame: 3 months
measure: Genomic changes of ctDNA and see if they are predictive of overall survival time.
timeFrame: 2 years
measure: Genomic changes of ctDNA and see if they are predictive of event-Free Survival.
timeFrame: 2 years
measure: Genomic changes of ctDNA and see if they are predictive of relapse-Free Survival.
timeFrame: 2 years
Other outcomes:
measure: Genetic and transcriptional profiling results.
timeFrame: From baseline (prior to initiation of conversion therapy)
Locations:
Study officials:
affiliation: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
name: Shuzhong Cui, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leal A, van Grieken NCT, Palsgrove DN, Phallen J, Medina JE, Hruban C, Broeckaert MAM, Anagnostou V, Adleff V, Bruhm DC, Canzoniero JV, Fiksel J, Nordsmark M, Warmerdam FARM, Verheul HMW, van Spronsen DJ, Beerepoot LV, Geenen MM, Portielje JEA, Jansen EPM, van Sandick J, Meershoek-Klein Kranenbarg E, van Laarhoven HWM, van der Peet DL, van de Velde CJH, Verheij M, Fijneman R, Scharpf RB, Meijer GA, Cats A, Velculescu VE. White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer. Nat Commun. 2020 Jan 27;11(1):525. doi: 10.1038/s41467-020-14310-3.
citation: Wang D, Cabalag CS, Clemons NJ, DuBois RN. Cyclooxygenases and Prostaglandins in Tumor Immunology and Microenvironment of Gastrointestinal Cancer. Gastroenterology. 2021 Dec;161(6):1813-1829. doi: 10.1053/j.gastro.2021.09.059. Epub 2021 Oct 2.
citation: Smyth EC, Gambardella V, Cervantes A, Fleitas T. Checkpoint inhibitors for gastroesophageal cancers: dissecting heterogeneity to better understand their role in first-line and adjuvant therapy. Ann Oncol. 2021 May;32(5):590-599. doi: 10.1016/j.annonc.2021.02.004. Epub 2021 Feb 17.