Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Durvalumab

Antineoplastic Agents, Immunological

A fixed dose of 1500 mg Q4W durvalumab (equivalent to 20 mg/kg Q4W) is used in the present study for patients \>30 kg (dosing by bodyweight only required for patients ≤30 kg).And Savolitinib will be administered orally 600mg once a day for 28 days as one cycle.

Durvalumab will be administered at 1500mg every 4 weeks from cycles 1 day 1.

Savoritinib 600mg will be administered orally a day for 28 days as one cycle.

Savolitinib

Jeeyun lee, Ph,MD

Jeeyun Lee, MD

Jeeyun Lee, Professor

For patients who failed primary chemotherapy with MET amplification, The efficacy and safety of the chemotherapy are evaluated by using dervalumab and saboritinib in combination.

Despite recent developments, the prognosis of patients with advanced gastric cancer is still poor, and the target treatment options studied in a recently completed randomized clinical trial in which patients with tumors expressing HER2 were treated with trastuzumab are proposed.

In this study, the survival period of patients treated with trastzumab was extended to less than 3 months. Despite these results, 80% of patients are still not eligible for trastzumab and need additional targeted therapy.

The largest somatic cell mutation frequency recorded in tumors can lead to higher renal antigen release and provision to the immune system. In addition, in some clinical trials, abnormal overexpression of MET was associated with poor clinical progress, rapid disease progression, and short survival period.

Double blocking of PD-1 and vascular endothelial growth factor receptor 2 appeared to increase inhibition of tumor growth compared to the treatment of each monoclonal antibody alone.

Therefore, in this study, the efficacy and safety of combination administration of immunoglobulin G1 that inhibits PD-L1 with MET amplification and Saboritinib (AZD6094), an MET inhibitor, are to be confirmed.

Histologically identified metastatic and recurrent gastric cancer, ECOG systemic activity of 0 or 1 and at least one measurable lesion in accordance with modified RECIST 1.1 According to the NGS results, the efficacy and safety of the combination administration of dervalumab and saboritinib are evaluated for gastric cancer patients scheduled for secondary and tertiary treatment with MET amplification.

Savoritinib is administered oral once a day at 600 mg (QD) every 28 days if it is more than 50 KG. Dervalumab is administered intravenously every four weeks from the first day of the first cycle CT will be used every 8 weeks from the first administration date to check the progress of the objective disease. Patients have evidence that they are resistant to treatment and useful in clinical trials, and if the supply of drugs is secured, they will continue to be treated with saboritinib and dervalumab.

Ph2 Study of Savolitinib and Durvalumab (MEDI4736) Combination in Advanced MET Amplified Gastric Cancer(VIKTORY-2)

Efficacy of savolitinib combination with durvalumab

Jeeyun Lee

Principal Investigator

Micronutrients

Docetaxel

Leucovorin

Fluorouracil

Tegafur

Oxaliplatin

Three preoperative and three postoperative cycles of SOX chemotherapy

A cycle consist of Day 1: Oxaliplatin 130mg/M2 intravenous Day 1-14 Tegafur gimeracil oteracil potassium capsule 80mg/M2 oral (twice daily)

Repeated every 21st day

Four preoperative and four postoperative cycles of FLOT chemotherapy

A cycle consist of Day 1 5-fluorouracil(5-FU) 2600mg/M2 administered via intravenous peripherally inserted central venous catheter(PICC) for 24 hour Leucovorin 200mg/M2 intravenous Oxaliplatin 85mg/ M2 intravenous Docetaxel 50mg/M2 intravenous

Repeated every 15th day

Perioperative chemotherapy will be administered according to description in two arms.

Chemotherapy

Birendra K Sah, Ph D

Birendra K Sah, PH D

Chen Li, PH D

Zhenggang Zhu, PH D

DRAGON III research, Neoadjuvant Chemotherapy (FLOT versus SOX) for Gastric Cancer, is an investigator initiated; phase 3, open label, multi-center randomized controlled study.

Non inferiority of SOX will be tested against FLOT. This study will be conducted at multiple center of China and will invite international centers to join it.The sponsor of this study is Ruijin Hospital and the project is supported by the Shanghai Key Laboratory of Gastric Neoplasms and Institute of Digestive Surgery, Shanghai.

Dragon III-Phase 3: Neoadjuvant Chemotherapy (FLOT Versus SOX) for Gastric Cancer

Efficacy Study of FLOT Versus SOX Regimen as Neoadjuvant Chemotherapy for Patients With Locally Advanced Gastric Cancer: A Phase 3 Multi-center Randomized Controlled Trial

Tumor regression grade (TRG), Becker criteria Grade 1a :Complete tumor regression: 0% residual tumor per tumor bed Grade 1b: Subtotal tumor regression: \<10% residual tumor per tumor bed Grade 2: Partial tumor regression: 10-50% residual tumor per tumor bed Grade 3: Minimal or no tumor regression: \>50% residual tumor per tumor bed

Overall survival Time from randomization to death from any cause

Disease free survival Time from randomization to relapse or death from any cause

Ruijin Hospital

Surgeon

Esophageal Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Pharmaceutical Solutions

Nivolumab

Ramucirumab

Rucaparib

Immune Checkpoint Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

* Rucaparib 600 milligrams twice daily
* Ramucirumab 8 milligrams per kilogram intravenous every 2 weeks
* Nivolumab 480 milligrams intravenous every 4 weeks
* Treatment will continue until disease progression, unacceptable toxicity or the patient desires to discontinue this therapy
* One dose level decrease of Rucaparib will be planned if toxicity develops in the first 6 patients
* 1 cycle= 28 days

* Rucaparib 600 milligrams twice daily
* Ramucirumab 8 milligrams per kilogram intravenous every 2 weeks
* Nivolumab 480 milligrams intravenous every 4 weeks
* Treatment will continue until disease progression, unacceptable toxicity or the patient desires to discontinue this therapy
* 1 cycle= 28 days

* Rucaparib 600 milligrams twice daily
* Ramucirumab 8 milligrams per kilogram intravenous every 2 weeks
* Treatment will continue until disease progression, unacceptable toxicity or the patient desires to discontinue this therapy
* 1 cycle= 28 days

Anwaar Saeed, MD

The study population is advanced gastric, gastroesophageal, and esophageal adenocarcinoma participants who have failed upfront standard of care chemotherapy. The goal is to demonstrate that Rucaparib plus Ramucirumab with or without Nivolumab has a higher response rate than what has been reported for Ramucirumab in previously treated patients. Trial will be a phase 1/2 trial. The Phase 1 portion will determine the recommended Phase 2 treatment dose for the combination of Rucaparib plus Ramucirumab and Nivolumab and enroll approximately 6-9 participants. The Phase 2 portion of the study will involve 52 participants allocated between two treatment groups comparing Rucaparib plus Ramucirumab with or without Nivolumab. The participants will be selected based on the results of a screening HRD gene panel.

Phase 1 - Safety Lead In - Enroll 6-9 molecularly unselected participants to determine the safety of the triplet combination of Rucaparib plus Ramucirumab and Nivolumab. One level dose de-escalation of Rucaparib will be planned based on dose limiting toxicity (DLT) signal of the first 6 participants run in phase.

Phase 2 - Parallel - Enroll 52 participants (26 in each cohort), open label, two treatment cohorts design evaluating Rucaparib plus Ramucirumab with or without Nivolumab. 50 percent (%) of participants enrollment to each treatment cohort will represent molecularly unselected population and the remaining 50% will be selected based on integrated screening tumor Homologous Recombination Deficiency (HRD) gene panel. The primary objective is efficacy by measuring the Overall Response Rate (ORR).

Rucaparib Plus Ramucirumab With or Without Nivolumab in Advanced Gastric and Esophageal Adenocarcinoma

A Phase I/II Trial of Rucaparib in Combination With Ramucirumab With or Without Nivolumab in Previously Treated Patients With Advanced Gastric and Esophageal Adenocarcinoma (RiME)

Defined as the highest dose studied for which the observed incidence of dose limiting toxicities (DLT) is less than 33%. DLTs will be measured per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Defined as the proportion of participants with overall response to therapy. Overall response is defined as the best response recorded, (including Complete Response (CR) and Partial Response (PR)), from the start of the treatment until the end of treatment. ORR will be measured per the Modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

Defined as the proportion of participants with overall benefit to therapy. Overall benefit is defined as the best response recorded, (including complete Response (CR), Partial Response (PR), and Stable Disease (SD)), from the start of the treatment until the end of treatment. Determine overall benefit of therapy using modified RECIST version 1.1

Reported as the proportion of participants that achieve PFS. PFS is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first. Measured per modified RECIST version 1.1

Defined as the time from the start of treatment until death due to any cause, reported as the mean of all participants' OS. Measured per the medical record.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ph2 Study of Savolitinib and Durvalumab (MEDI4736) Combination in Advanced MET Amplified Gastric Cancer(VIKTORY-2)	NCT05620628	Stomach Cancer,...	Durvalumab Savolitinib	19 Years -	Samsung Medical Center
Dragon III-Phase 3: Neoadjuvant Chemotherapy (FLOT Versus SOX) for Gastric Cancer	NCT04384601	Gastric Cancer Neoadjuvant Che...	Chemotherapy	18 Years - 80 Years	Ruijin Hospital
Rucaparib Plus Ramucirumab With or Without Nivolumab in Advanced Gastric and Esophageal Adenocarcinoma	NCT03995017	Esophagus Cance... Stomach Cancer,...	Rucaparib Ramucirumab Nivolumab	18 Years -	University of Kansas Medical Center
Dragon III-Phase 3: Neoadjuvant Chemotherapy (FLOT Versus SOX) for Gastric Cancer	NCT04384601	Gastric Cancer Neoadjuvant Che...	Chemotherapy	18 Years - 80 Years	Ruijin Hospital

Spots Global Cancer Trial Database for stomach cancer, adenocarcinoma