Biomarker Analysis of HIPEC Combined With PD1/PDL1 Inhibitor for Gastric Cancer With Peritoneal Metastasis

Gastric Cancer Clinical Trial

Official title:

Integrated Biomarker Analysis for Hyperthermic Intraperitoneal Chemotherapy(HIPEC) Combined PD1/PDL1 Inhibitor Treatment in Patients of Advanced Gastric Cancer With Peritoneal Metastasis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05661110
• Other study ID #: HIPEC-11
• Status: Not yet recruiting
• Start date: January 1, 2023
• Est. completion date: December 31, 2027

Study information

• Verified date: December 2022
• Source: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Contact: Ziying Lei, Doctor
• Phone: (086)020-66673666
• Email: leiziyinggz[@]126.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 46
• Est. completion date: December 31, 2027
• Est. primary completion date: March 31, 2025
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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;

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Other:
• Observational
All patients will be treated with standard of conversion treatment with HIPEC combined PD1/PDL1 inhibitor. After obtaining written informed consent, participants will have serial blood, tumor tissue collection. The blood collection (10 ml) should coincide with routine clinical blood draw to minimize participant discomfort if possible. No additional procedures will be performed other than phlebotomy. Participants will remain on the study for as long as they are being followed or treated at Affiliated Cancer Hospital & Institute of Guangzhou Medical University. Participants can withdraw from the study at any time.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Affiliated Cancer Hospital & Institute of Guangzhou Medical University

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Genetic and transcriptional profiling results.	Mutation and transcriptomic information will be recorded by NGS using AmoyDx® Master Panel, which contains 559 genes for DNA mutation detection and 1813 genes for RNA expression and fusion detection.	From baseline (prior to initiation of conversion therapy)
Primary	Relationship between the status, numerical changes of ctDNA during HIPEC combined with PD1/PDL1 inhibitor conversion therapy and postoperative R0 resection rate.	R0 resection rate refers to the proportion of all patients with negative margins under the microscope of tumor specimens after surgery to the total number of participants. To dynamically evaluate the ctDNA profiles by next-generation sequencing and illustrate the genomic changes of ctDNA at baseline, during treatment.	3 months
Secondary	Genomic changes of ctDNA and see if they are predictive of ORR.	Objective response rate(ORR): ORR = (number of subjects with complete response (CR) + partial response (PR))/total number of subjects ×100%. Measurable lesion according to the Response Evaluation Criteria In Solid Tumours(RECISTv1.1). To dynamically evaluate the ctDNA profiles by next-generation sequencing and illustrate the genomic changes of ctDNA at baseline, during treatment.	3 months
Secondary	Genomic changes of ctDNA and see if they are predictive of overall survival time.	Overall survival time(OS) refers to the time of first use of the drug to the time of death. At the end of the study, if the subject is still alive, refer the known "date of last survival of the subject" as the date of censoring. To dynamically evaluate the ctDNA profiles by next-generation sequencing and illustrate the genomic changes of ctDNA at baseline, during and after treatment.	2 years
Secondary	Genomic changes of ctDNA and see if they are predictive of event-Free Survival.	Event-Free Survival(EFS): Defined as the interval between the first conversion therapy and the first recorded related events, including preoperative disease progression, postoperative disease recurrence, and death from any cause. To dynamically evaluate the ctDNA profiles by next-generation sequencing and illustrate the genomic changes of ctDNA at baseline, during and after treatment.	2 years
Secondary	Genomic changes of ctDNA and see if they are predictive of relapse-Free Survival.	Relapse-Free Survival(RFS): Defined as postoperative the first recorded postoperative recurrence of disease or death from any cause. To dynamically evaluate the ctDNA profiles by next-generation sequencing and illustrate the genomic changes of ctDNA at baseline, during and after treatment.	2 years