AUTHOR=Yu Yang , Yu Rong , Wang Na , Bai Yuping , Shi Qianling , Maswikiti Ewetse Paul , Chen Hao 

TITLE=Photodynamic therapy in combination with immune checkpoint inhibitors plus chemotherapy for first-line treatment in advanced or metastatic gastric or gastroesophageal junction cancer: A phase 2–3 clinical trial protocol

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1063775

DOI=10.3389/fphar.2023.1063775

ISSN=1663-9812

ABSTRACT=Introduction: The immune checkpoint inhibitor (ICI) has been approved as the first-line therapy for metastatic gastric cancer in China. The treatment response of ICI is highly dependent on the immune condition within the tumor microenvironment. Photodynamic therapy (PDT) has a long history in cancer treatment, and recent studies showed it had an immunomodulatory effect on the tumor. Here we will conduct a trial to assess whether or not a combination with PDT will improve the outcomes of ICI-based treatment in patients with advanced or metastatic gastric cancer. 
Methods: This study is a single-center, open-label, randomized controlled, phase 2-3 trial. Patients (18-65 years old) with untreated gastric or gastroesophageal junction adenocarcinoma will be eligible for this trial. Sixty participants will be enrolled and randomly divided into the test group (n=30) and control group (n=30) to receive PDT in combination with ICI plus chemotherapy and ICI plus chemotherapy, respectively. The primary is progression-free survival (PFS). The secondary outcomes include objective response rates (ORR) and the occurrence of adverse events. In addition, we will also assess the changes in peripheral blood mononuclear cells (PBMCs) and tumor microenvironment after PDT treatment in the test group. Evaluation of the tumor response will be performed every two cycles for a maximum of eight cycles. 
Discussion: PDT has an immunomodulatory effect on the tumor microenvironment; however, this has not been demonstrated for gastric cancer in a clinical trial. Based on our experience of PDT treatment in digestive tract tumors, we plan to conduct a randomized controlled trial on this topic. This will be the first study to evaluate the synergistic effect of PDT with immunochemotherapy for patients with advanced gastric cancer.
Ethics and dissemination: It was approved by the Institutional Research Ethics Committee of Lanzhou University Second Hospital (No. 2022A-491). When this trial is completed, it will be shared at conferences and submitted for a potential publication in a peer-reviewed journal. 
Trial registration: It was registered at http://www.chictr.org.cn/ (registered number: ChiCTR2200064280).