Clinical Research Directory

Timing of Minimally Invasive Local Treatment After First-Line Systemic Therapy in Oligometastatic Esophageal or Gastric Adenocarcinoma

Purpose of the Study: This clinical study investigates whether a shorter or longer duration of systemic therapy before local treatment (surgery or radiation) results in better disease control in patients with esophageal or gastric cancer with a limited number of metastases, also known as oligometastases. Background: In about 25% of patients with advanced esophageal or gastric cancer, the disease spreads to only a few sites (oligometastatic disease). Prior studies suggest that local treatment after systemic therapy may extend survival in this subgroup. However, it is unclear how long systemic therapy should last before initiating local treatment. The OMEC-5 study aims to clarify this and identify potential biomarkers for treatment response. Study Design: Initiated by Amsterdam UMC and UMCU and conducted in multiple hospitals across Europe. Total of 414 patients to be enrolled. Duration: \~53 months (35 months enrollment + 18 months follow-up). Approved by the medical ethics committee at Amsterdam UMC. Procedure: Eligibility screening: Includes physical exam, blood tests (incl. circulating tumor cells), medical history review, and confirmation of oligometastases by an expert panel. Initial treatment: All participants receive 4 months of standard systemic therapy (chemotherapy + immunotherapy and/or targeted therapy depending on tumor markers like HER2 or Claudin 18.2). Response assessment (Review 1): Imaging and/or laparoscopic examination. If oligometastases persist and tumors have not progressed, participants are randomized into two groups: Group A (longer systemic therapy): 4 more months of systemic therapy, then local treatment if disease is stable, followed by 4 months of immunotherapy ± targeted therapy. Group B (shorter systemic therapy): Immediate local treatment followed by 4 months of systemic therapy, then reassessment and potentially 4 months of immunotherapy ± targeted therapy. Follow-up: Regular scans and quality-of-life questionnaires (5 times), and periodic blood sampling (4 times). Treatments Involved: Chemotherapy: CapOx or FOLFOX Immunotherapy: nivolumab or pembrolizumab Targeted therapy: trastuzumab (HER2-positive) or zolbetuximab (Claudin 18.2-positive) Potential Benefits and Risks: Patients may benefit from better disease control and a personalized treatment strategy. Known side effects relate to the standard treatments used (chemo, immuno, targeted therapies), and no extra medical risk is expected beyond routine care. Possible inconveniences include blood draws, scans, minor surgery (laparoscopy), and time investment. Data and Sample Handling: Personal data and tumor/blood samples are coded and securely stored. Data may be used for future cancer research if the patient consents. Participants can withdraw at any time. Confidentiality and Privacy: Patient data are kept confidential, and participants have rights to access or delete their data. Privacy measures comply with GDPR and Dutch law. Compensation and Insurance: Participation is voluntary, with no financial compensation. Standard treatment costs are covered by healthcare insurance. No extra insurance is required, as the treatment aligns with standard care practices.

Evaluation of Efficacy and Safety De-escalation Versus Standard Adjuvant Chemotherapy in Patients With Low Risk Localized Gastroesophageal Adenocarcinoma

The ATTENUATION study targets patients with gastric adenocarcinoma (GA), esophageal adenocarcinoma (EAC) or gastro-esophageal junction (GEJ) who have received 4 cycles of FLOT chemotherapy before the surgery. Standard post-operative management consists of chemotherapy with 4 cycles of FLOT. However, the nature and duration of postoperative treatment are standardized and are not adapted to the specific tumor response of each patient. All patients are therefore referred to the same treatment regimen. As a result, good responders (defined in particular by wide resection of the tumor and a good response to preoperative chemotherapy on the tumor removed during surgery) may be over-treated and exposed to unnecessary adverse events. Only 50-60% of patients can start chemotherapy post-operatively, due to the potential residual adverse effects associated with surgery in particular. Thus, it would appear that preoperative chemotherapy is the most important factor in the overall efficacy of the treatment sequence. Moreover, numerous retrospective studies have reported a favorable outcome in patients with a major response to pre-operative treatment but who were unable to receive post-operative chemotherapy. The hypothesis of this study is that surveillance after surgery in patients with gastric or gastroesophageal junction tumors, with a good response to preoperative chemotherapy could provide significant clinical benefit and favorable disease progression. Participants will: * be distributed in one of the two arms * will be followed up every 3 months for 2 years, then every 6 months (clinical examination, imaging, quality-of-life questionnaire) subsequent years until 3 years after the randomization of the last patient. * followed up until their death or their progression whether local, regional or metastatic.

Efficacy of Tirellizumab Combined With Oral, Intravenous and Abdominal Chemotherapy in Peritoneal Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma

For peritoneal metastatic gastric/gastroesophageal junction adenocarcinoma (cT3-4NanyM1), PD-1 antibody combined with chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) can downstage tumor stage, increase the conversion resection rate, and may improve the long-term survival. Tislelizumab, an anti-PD-1 antibody, has recently been proved in the first- and second-line standard treatment for advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma.In the subgroup analysis of RATIONALE-305 trial, tislelizumab also showed good efficacy in gastric/gastroesophageal junction adenocarcinoma patients with peritoneal metastasis. Combination of tirellizumab,SOX and HIPEC for peritoneal metastatic gastric/gastroesophageal junction adenocarcinoma could be a novel therapeutic strategy to increase response rate and therapeutic efficacy. This study is a monocenter, single-arm phase 2 clinical trial to evaluate tolerability, safety and efficacy of perioperative tirellizumab in combination with SOX and HIPEC in peritoneal metastatic gastric/gastroesophageal junction adenocarcinoma.