Clinical Research Directory

A Phase 2 Study of Neoadjuvant Docetaxel, Oxaliplatin, S-1 in Patients With Unresectable Locally Advanced or Distant Metastasis Limited to Lymph Node Gastric Cancer

Gastric cancer is the fifth most common carcinoma in the world, and cancer-related deaths rank third. It is one of the main causes of death from cancer in Korea. The cure method for gastric cancer is radical resection, but in most patients, radical resection is impossible due to local infiltration or peripheral organ or distant metastasis. Many assisted chemotherapy has been studied to improve survival rate, and in East Asia, assisted chemotherapy after complete D2 resection is the standard treatment. In the West, on the other hand, preoperative chemotherapy and postoperative assisted chemotherapy are currently standard treatments. However, due to the limited effect of adjuvant chemotherapy, it has been reported that better clinical course can be improved by increasing anticancer intensity. In this context, a large number of prior chemotherapy have been attempted, and prior chemotherapy has several potential effects as follows. (1) Improvement of R0 resection rate due to reduced primary cancer size, (2) early treatment for micro metastasis, (3) evaluation of treatment response rate in patients with measurable lesions, and (4) unnecessary laparotomy can be avoided in patients with biologically aggressive diseases. Based on the efficacy of chemotherapy in the combination of docetaxel, fluoropyrimidine, and platinum in metastatic gastric cancer, the investigators conducted a preceding auxiliary anti-cancer clinical trial of docetaxel, capecitabine and cisplatin in advanced gastric cancer patients who could not be completely resected by surgery. DXP was performed 4-6 cycles before surgery with the recommended dose in phase 1-2. In a total of 49 patients, R0 resection was performed in 31 (63%), and among patients, R0 resection was improved in cases where resection was not possible due to local infiltration (71%) and in cases where para-aortic node metastasis was performed (73%). We have reported that docetaxel, oxaliplatin, and S-1 chemotherapy (DOS) as preoperative adjuvant therapy can be safely administered in combination with D2 gastrectomy and postoperative adjuvant therapy S-1 in potentially resectable local progressive gastric cancer patients. R0 resection was achieved in 97.6% of patients, and pathological complete remission was observed in 19.5%. Based on this, a phase 3 PRODIGY study was performed to evaluate the benefit of S-1 (CSC group) as a preoperative prior chemotherapy compared to S-1 (SC group) as a postoperative adjuvant therapy in gastric cancer of cT2/3N+ or cT4Nany stage, and 0.75% of the CSC group was administered HR. In the patient group undergoing surgery, the R0 resection rate was 95% in the CSC group and 84% in the SC group. In the CSC group, the pathological complete remission rate was 10.4%. Based on these results, a clinical trial of DOS as a preoperative chemotherapy was planned for progressive gastric cancer that could not be resected due to local progression or metastasis limited to remote lymph nodes. Primary goal: Evaluation of R0 resection rate in patients who underwent prior chemotherapy as a clinical trial. Secondary objective: safety evaluation, overall survival period, progression-free survival period, pathological complete remission rate, and investigation of biological markers.

Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer

Despite recent advances, the prognosis of patients with advanced gastric cancer remains poor. At present, regimens that combine a platinum and fluorouracil agent either alone or in combination with a third drug such as epirubicin or taxane constitute the most effective treatment option in the first-line metastatic setting, resulting in a median OS of approximately 10 months. In the second-line setting, ramucirumab (a vascular endothelial growth factor receptor 2 antagonist) was recently approved by the United States Food and Drug Administration, and has demonstrated modest activity in patients with advanced gastric or GEJ adenocarcinoma who progressed after first-line platinum- or fluoropyrimidine-containing chemotherapy. Median OS was 5.2 months in the ramucirumab group versus 3.8 months in the placebo group. At the updated DCO of 03 June 2020 in the DS8201-A-J202 (DESTINY-Gastric01) study in HER2-positive GC or GEJ adenocarcinoma subjects assigned to T-DXd 6.4 mg/kg, T-DXd further demonstrated clinically meaningful efficacy. The median OS was 12.5 months for the T-DXd group and 8.9 months for the physician's choice group (HR = 0.60, 95% CI: 0.42, 0.86). In a prespecified subgroup analysis, the percentages of patients with an objective response were analyzed in HER2-low group. The response rate in HER2 2+ was 29% (8 of 28) with T-DXd monotherapy. Refer to the figure below for the response rate in HER2-low group in previous DESTINY trials. This is a two part, phase I/Ⅱ, open-label, single center study of afatinib in combination with T-DXd, in 2L/3L gastric cancer patients with HER2-low. The study design allows an investigation of combination dose of afatinib with T-DXd, with intensive safety monitoring to ensure the safety of the patients.

Omentum Preservation Versus Complete Omentectomy in Gastrectomy for Gastric Cancer

Curative therapy for gastric cancer usually consists of perioperative chemotherapy and a radical (R0) gastrectomy. A radical resection includes a modified D2 lymphadenectomy, and, generally, a complete omentectomy, to ensure the removal of omental metastatic lymph nodes and tumor deposits. The omentum has some essential functions within the peritoneal cavity. The omentum functions as regulator of regional immune responses to prevent infections and, additionally, it prevents adhesions that can lead to small bowel obstruction. Omentectomy is associated with increased incidence of early and late postoperative complications such as abdominal abscess, ileus, and wound infections in various types of surgery. There is little evidence regarding survival benefit of routine complete omentectomy during gastrectomy. The investigators hypothesize that omitting a complete omentectomy (and instead preserve the greater omentum distal of the gastroepiploic arcade) during gastrectomy for cancer does not negatively impact survival. OMEGA is a randomized controlled, open, parallel, non-inferiority, multicenter trial. Adult patients (\>18 years) with primary resectable gastric cancer, clinical stage T2-4a N0-3 M0 or cT1N+ scheduled for open or minimally invasive (sub)total gastrectomy are included. The primary study objective is to investigate whether omentum preservation in gastrectomy for cancer is non-inferior to complete omentectomy in terms of three-year overall survival.

A Phase Ib/II Trial of Neoadjuvant Zolbetuximab Plus Docetaxel, Oxaliplatin and S-1 Chemotherapy in Patients With Locally Advanced Gastric Cancer

Claudin 18.2 is a promising therapeutic target overexpressed on the surface of gastric cancer cells. The addition of zolbetuximab, the monoclonal antibody targeting Claudin 18.2 to chemotherapy in two recent Phase 3 studies prolonged survival outcomes, indicating that Claudin 18.2 is a valid target in gastric cancer. Asan Medical Center researchers conducted a study on Claudin 18.2 expression in patients with operable gastric cancer and defined moderate to strong claudin expression in more than 75% of tumor cells as Claudin 18.2 overexpression, which was observed in 46.5% of patients with stage I-III tumors. This suggests that zolbetuximab-based treatment may be possible in patients with LAGC. Therefore, The investigator designed a prospective, multicenter, open-label, Phase Ib/II study to determine the efficacy and safety of zolbetuximab/DOS as neoadjuvant chemotherapy in patients with LAGC.

Gastrectomy + Cytoreductive Surgery + HIPEC for Gastric Cancer With Peritoneal Dissemination.

A randomized controlled two-armed phase III trial for gastric cancer patients with peritoneal dissemination. Randomization between gastrectomy + cytoreductive surgery + HIPEC (experimental arm) and palliative systemic chemotherapy (standard arm).

Total Neoadjuvant FLOT Chemotherapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer

The main goal of this study is to investigate the proportion of participants with locally advanced gastric and gastroesophageal adenocarcinoma without previous treatment during the last 5 years who can tolerate all planned cycles of chemotherapy and radical surgical treatment who will be prospectively randomized into two groups to undergo one of two chemotherapy regimens, followed by surgery: 1. 8 cycles of Total Neoadjuvant ChemoTherapy (TNT) with 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin, and Docetaxel (FLOT) followed by surgery. 2. 4 cycles of Neoadjuvant FLOT chemotherapy scheme preoperatively and 4 adjuvant FLOT cycles postoperatively.

Validation of a Molecular Test for Risk-stratification of Patients With High-risk Intestinal Metaplasia (GCEP2 Study)

This study is carried out to find out if a customized molecular test can identify a subgroup of patients with very-high-risk of developing stomach cancer within patients with intestinal metaplasia (IM). The investigators hypothesise that the incidence of dysplasia and GC cases in the molecular-test-positive group will be significantly higher than that in the molecular-test-negative group. Such a test has the potential to guide clinicians to better manage patients with IM by allowing endoscopic surveillance to be focused on individuals at very-high-risk of developing stomach cancer, at the same time avoiding or reducing endoscopies for those at lower risk.

Gastric Cancer' Textbook Oncological Outcome and Tumor Board Performance

The goal of this observational, no-profit, spontaneous, retrospective, monocentric study is to compare surgical and oncologic outcomes in patients affected by gastric cancer before and after the institution of the Tumor Board, a multidisciplinary weekly case discussion. The main question it aims to answer is whether the Textbook Outcome (TO) and Textbook Oncological Outcome (TOO) of patients with non-early, non-metastatic gastric cancer undergoing surgical treatment with curative intent have improved before (from January 2018 to November 2019) and after (from December 2019 onwards) the establishment of the Multidisciplinary Tumor Board (MTB) at Fondazione Policlinico Gemelli (FPG).

Rehabilitation and Recovery for Persons with Esophageal or Gastric Cancer

This study aims to develop and evaluate a model for systematic and evidence-based cancer rehabilitation for people with esophageal and gastric cancer to provide conditions for a better quality of life and fewer cancer-related symptoms.

Second-Line Chemotherapy With Ramucirumab +/- Paclitaxel in Elderly Advanced Gastric or Gastroesophageal Junction Cancer Patients

The primary objective is to evaluate six months survival rate and quality of life at 4 months of ramucirumab alone or in combination with paclitaxel in patients aged 70 years or more who have stomach or GEJ adenocarcinoma and whose first line of fluoropyrimidine- and platinumcontaining treatment has failed. The co-primary endpoints are the following: * Six months survival rate * Quality of life at 4 months as assessed by the following three target dimensions of the EORTC QLQ-ELD14 questionnaire: mobility, illness burden and worries about the future

Exploring the Difference Between Gastric Cardia Cancer and Non-cardia Gastric Cancer Based on Multiomics

This is an observational study with a case control design. This study included patients with gastric cancer confirmed by pathological diagnosis of gastric tissue, and matched the control population according to age, gender, etc. In this study, researchers collected clinical information and multiple biological samples such as saliva, serum, and feces from the study subjects. We combined 16S rRNA sequencing and metabolomics to explore the differences in microbial and metabolic characteristics between gastric cardia cancer and non-cardia gastric cancer for early screening of gastric cancer.

Radiotherapy + Chemoimmunotherapy Followed by Surgery in Patients With Limited Metastatic Gastric or GEJ Cancer

The goal of this clinical trial is to evaluate the efficacy and safety of radiotherapy combined with chemotherapy and anti-PD-1 immunotherapy followed by surgery for the primary and metastatic lesions in patients with limited metastatic gastric or gastroesophageal junction adenocarcinoma. The main questions it aims to answer are: 1) If the multimodal treatment which includes anti-PD-1 immunotherapy and local therapies will improve the survival of this group of patients. 2) If the multimodal treatment which includes anti-PD-1 immunotherapy and local therapies can be performed safely in this group of patients. Participants will receive short course hypofractionated radiotherapy (HFRT) for the primary lesion, HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, combined with systemic chemotherapy and anti-PD-1 immunotherapy. For patients with HER2-positive cancer (defined as IHC 3+ or 2+/ISH+), trastuzumab is used along with chemotherapy and anti-PD-1 antibody. Then, surgical resections of primary and metastatic lesions are performed as much as possible. For patients who need a widely invasive surgical approach or are inoperable, local ablative therapies such as radiofrequency ablation (RFA) and microwave ablation (MVA) can be alternatives. For patients undergoing surgical resections, postoperative treatment includes chemotherapy, which is determined by the researcher, and PD-1 antibody, which will be maintained until one year after surgery.

Capeox Regimen Combined With Sintilimab and Bevacizumab for Gastric Cancer

The median survival time of first-line chemotherapy for advanced gastric cancer is about one year, and the treatment is still facing the bottleneck. This is a one-arm, open and prospective phase II clinical study. Recruit patients who have been diagnosed with advanced or metastatic adenocarcinoma of the stomach and gastroesophageal junction and have not received systematic treatment.

Laparoscopic vs. Open Distal Gastrectomy After Neoadjuvant Chemotherapy

The study was designed as single-country, multi-center, open-labelled, randomized (1:1), phase II trial. 238 patients with medically and technically operable advanced gastric adenocarcinoma in middle or distal 1/3 of stomach are enrolled and randomly assigned to laparoscopic gastrectomy group and open gastrectomy group. 4 cycles of mFLOT chemotherapy will be conducted before and after gastrectomy. The primary objective of this study is comparison of D2 lymph node dissection compliance rate between open surgery group and laparoscopic surgery group after neoadjuvant chemotherapy.