Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Fluorouracil

Cisplatin

Immunomodulating Agents

Patients with gastric cancer and verified free cancer cells who receive 1 course of intraperitoneal immunotherapy with interleykin-2 + 3 courses of systemic chemotherapy (Cisplatin + 5-FU). In case of downstaging (M1 -\> M0) surgical treatment will be performed.

Patients with gastric cancer and verified free cancer cells who receive 3 courses of systemic chemotherapy (Cisplatin + 5-FU). In case of downstaging (M1 -\> M0) surgical treatment will be performed.

neoadjuvant chemoimmunotherapy

Igor Khatkov, Professor, PhD

Roman Izrailov, Professor, PhD

Nikolay Semenov

Boris Pomortsev

The purpose of this study is to determine whether intraperitoneal immunotherapy (with interleykin-2 - human cytokine reaction activator) with systemic chemotherapy will be more effective than systemic chemotherapy alone in patients with gastric cancer and verified free cancer cells in abdominal cavity in improving the long term outcomes and overall survival of further surgical treatment.

The Efficacy of Surgical Treatment After Neoadjuvant Chemotherapy Plus Intraperitoneal Immunotherapy Versus Chemotherapy Alone for Patients With Positive Wash Cytology Gastric Cancer

Prospective Randomized Phase II Clinical Trial: the Efficacy of Surgical Treatment in Combinations With Intraperitoneal Immunotherapy and Systemic Chemotherapy in Patients With Gastric Cancer and Verified Free Cancer Cells

Overall 2-year survival for patients who received radical (R0) surgical treatment after downstaging (M1 -\> M0; Cyt "+" -\> Cyt "-") with initial free cancer cells in the abdominal cavity without macroscopic canceromathosis.

Portability of the systemic therapy methods (intraperitoneal immunotherapy and systemic chemotherapy). Toxicity scale.

Mortality related to intraperitoneal immunotherapy and systemic chemotherapy It is defined as the death within 24 months from the start of the treatment regardless of the reason.

Number of patients that were downstaged (M1 -\> M0; Cyt "+" -\> Cyt "-") with initial free cancer cells in the abdominal cavity without macroscopic canceromathosis.

Number of postoperative morbidity and mortality in the early post-operative period (for patients who received radical (R0) surgical treatment after downstaging)

Moscow Clinical Scientific Center

Symptoms and General Pathology

Infections

Neoplasm Metastasis

Virus Diseases

Adenoviridae Infections

Tegafur

Oxaliplatin

Interleukin-12

This study intends to enroll Her2-negative subjects with first-line treatment of peritoneal metastasis from gastric cancer. Subjects will be treated with BioTTT001 intraperitoneal perfusion combined with SOX and toripalimab after completing the screening period, and the subjects will first receive BioTTT001 monotherapy treatment with BioTTT001 1×10\^10 VP intraperitoneal perfusion (P.I.), D1 and D3, and enter the combination therapy stage 7 days (±1d) after the first dose of BioTTT001.Subjects will be treated with the regimen as follows: BioTTT001 injection, 1×10\^10 VP P.I., D1；toripalimab 160mg intravenous (i.v.), D1; Oxaliplatin 130mg/m\^2 i.v. , D1 ; Tegafur 40\~60mg Bis in die（b.i.d.） Peroral（p.o.）D1\~D14; 3 weeks per cycle.

Monotherapy lead-in phase: BioTTT01 1×10\^10 VP, i.p., D1 and D3; Combination therapy phase: BioTTT01 1×10\^10 VP, i.p., D1 and D3, 3 weeks per cycle

BioTTT001 intraperitoneal infusion

Combination therapy phase: Oxaliplatin 130 mg，i.v., D1 and D3, 3 weeks per cycle; Tegafur 40\~60mg b.i.d. p.o. D1\~D14; 3 weeks per cycle

SOX regimen

Combination therapy phase: toripalimab 160mg i.v. D1, 3 weeks per cycle.

toripalimab

Shuhui Song, bachelor

Zhenning Wang, MD

Funan Liu, MD

This is a phase I, single arm, open-label clinical study of BioTTT001 in combination with SOX and Toraplizumab in patients with peritoneal metastases from gastric cancer.

This study intends to enroll Her2-negative subjects with first-line treatment of peritoneal metastasis from gastric cancer. Subjects will be treated with BioTTT001 intraperitoneal perfusion combined with SOX and toripalimab after completing the screening period, and the subjects will first receive BioTTT001 monotherapy treatment with BioTTT001 1×10\^10 viral particle (VP) intraperitoneal perfusion (P.I.), D1 and D3, and enter the combination therapy stage 7 days (±1d) after the first dose of BioTTT001.Subjects will be treated with the regimen as follows: BioTTT001 injection, 1×10\^10 VP P.I., D1；toripalimab 160mg intravenous (i.v.), D1; Oxaliplatin 130mg/m\^2 i.v. , D1 ; Tegafur 40\~60mg Bis in die（b.i.d.） Peroral（p.o.）D1\~D14; 3 weeks per cycle.

A Clinical Study of BioTTT001 in Combination With SOX and Toripalimab in Patients With Gastric Cancer

A Clinical Study to Evaluate the Safety and Efficacy of Recombinant Human nsIL12 Oncolytic Adenovirus Injection (BioTTT001) in Combination With SOX and Toripalimab in Patients With Peritoneal Metastases From Gastric Cancer

Objective response rate (ORR) as assessed by the investigators

The time from the start of treatment to progress disease or death for any cause

The time from the start of treatment to death for any cause

Beijing Bio-Targeting Therapeutics Technology Co., Ltd

China Medical University, China

professor

Paclitaxel

Albumin-Bound Paclitaxel

HIPEC treatment (paclitaxel, at 43°C for 60 min) was performed on the 1st day after the first exploratory laparotomy and on the third day after the radical surgery for a total of 2-3 times (total amount of paclitaxel was 175 mg/m2 ). Systemic therapy was started 3 weeks after HIPEC. Systemic therapy including: Tirilizumab: 200 mg, Q3W; oxaliplatin: 130mg/m2, Q3W; Herceptin: loading dose of 8 mg/kg followed by 6 mg/kg Q3W. Tegeo: Oral administration: 40 mg per dose for BSA \<1.25, 50 mg per dose for BSA 1.25 to 1.5, and 60 mg per dose for BSA ≥1.5, twice daily for each treatment cycle Q3W; After 2-6 weeks, laparoscopic exploration was performed, PCI score was calculated, and radical surgery was performed in patients who were eligible for radical surgery. Postoperative HIPEC was performed twice.

In the experimental group, HIPEC treatment (paclitaxel, 3000 ml of physiological saline at 43°C for 60 min) was performed on the first day after the first exploratory laparotomy and on the third day after the radical surgery for a total of 2-3 times (total amount of paclitaxel was 175 mg/m2 ), with an interval of not more than 72 h. Intravenous systemic therapy was started 3 weeks after the completion of HIPEC treatment. systemic therapy.

HIPEC

1. Tirilizumab: 200 mg, i.v., D1, Q3W;
2. oxaliplatin: 130mg/m2, i.v., D1, Q3W;
3. Herceptin: a tri-weekly dosing regimen with an initial loading dose of 8 mg/kg followed by 6 mg/kg Q3W.
4. Tegeo: Oral administration: 40 mg per dose for BSA \<1.25, 50 mg per dose for BSA 1.25 to 1.5, and 60 mg per dose for BSA ≥1.5, twice daily for each treatment cycle D1-D14, Q3W;

Systemic therapy

Fengyuan Li, PhD

Yigang Zhang, PhD

Zekuan Xu, PhD

Gastric cancer (GC) with peritoneal metastasis has a poor prognosis and short survival. In recent years, heat intraperitoneal perfusion chemotherapy (HIPEC) has gained better efficacy in the treatment of peritoneal metastases of many malignant tumors, including GC with peritoneal metastasis. The use of immune checkpoint inhibitors (ICIs) in the treatment of advanced GC has made significant progress in recent years. And studies showed that patients who were responded to immunotherapy combined with chemotherapy as the first-line treatment were able to achieve significant survival benefit after radical resection. However, whether HIPEC combined with immunotherapy for peritoneal metastatic gastric cancer improves the R0 resection rate and prolongs survival time is currently unclear. Therefore, we conducted this prospective multicenter clinical trial to explore the effective dose and safety of the combination of systemic chemotherapy, HIPEC, anti-PD-1 and anti-HER-2 therapy, which will provide a clinical basis for the treatment of advanced GC.

Gastric cancer (GC) is the 5th most common malignant tumor worldwide, and it causes the 4th most tumor-related deaths among all malignant tumors. China is a large country with 40% of the total number of GC cases worldwide. Despite the advances in medical detection methods, most of the GC patients in China are in the advanced stage at the time of diagnosis, in which peritoneal metastasis is one of the common metastatic patterns of advanced GC, and the presence of peritoneal metastasis accounts for about 46% of patients with distant metastasis detected at the first diagnosis. The prognosis of GC patients with peritoneal metastasis is extremely poor, and compared with other metastatic organs, patients with stage IV GC with peritoneal metastasis have a worse prognosis and shorter survival.

The treatment of peritoneal metastasis of GC has been based on systemic chemotherapy with reference to advanced GC, but it is difficult for traditional chemotherapeutic agents to reach the peritoneal lesions due to the existence of blood-peritoneal barrier. In recent years, heat intraperitoneal perfusion chemotherapy (HIPEC) has gained better efficacy in the treatment of peritoneal metastases of many malignant tumors, including GC.HIPEC allows chemotherapeutic drugs to act directly on tumor tissues while reducing the impact on other parts of the body; the warming effect is synergistic with the antitumor effects of chemotherapeutic drugs and helps the drugs to act more efficiently on the intraperitoneal tumor cells; moreover, the chemotherapeutic drugs are absorbed through the peritoneum and then enter the liver via the portal vein route, which is beneficial to preventing liver metastasis. HIPEC currently has four applications and indications in the clinic: firstly, palliative application to improve the quality of life for GC abdominal metastasis with a large amount of carcinomatous ascites; secondly, therapeutic application of radical gastric cancer surgery + cytoreductive surgery + HIPEC for the treatment of GC; third, prophylactic application, radical gastric cancer surgery + peritoneal hyperthermia chemotherapy, targeting people with high risk of peritoneal recurrence, especially patients with T3-4 or positive lymph nodes; fourth, neoadjuvant application, neoadjuvant chemotherapy combined with peritoneal hyperthermia chemotherapy before radical gastric cancer treatment, in order to reduce the risk of peritoneal implantation of gastric cancer and to increase the possibility of radical surgery. However, there is a lack of high-level evidence-based medical evidence on the efficacy and safety of HIPEC as a translational treatment for GC with peritoneal metastasis.

The use of immune checkpoint inhibitors (ICIs) in the treatment of advanced GC has made significant progress in recent years. The KEYNOTE series of studies evaluated the safety and efficacy of PD-L1 antibody as a first-line treatment for advanced GC, among which the results of KEYNOTE-859 confirmed that the combination of Pembrolizumab and chemotherapy is expected to be a HER-2 negative advanced gastric/esophagogastric junctional cancer first-line treatment option. A recent retrospective study by Chinese scholars demonstrated that patients with stage IV GC who were responded to the immunotherapy combined with chemotherapy as the first-line treatment were able to achieve significant survival benefit after radical resection. However, whether HIPEC combined with immunotherapy for peritoneal metastatic gastric cancer improves the R0 resection rate and prolongs survival time is currently unclear.

Therefore, we conducted this prospective multicenter clinical trial trying to combine the specificity of HIPEC for peritoneal metastases with immunotherapy for advanced GC, aiming to evaluate the efficacy and feasibility of multimodal treatment regimens, such as HIPEC in combination with immunotherapy, for the transformative treatment of peritoneal metastases of GC or EJ junctional cancer and to explore the effective dose and safety of the combination of systemic chemotherapy, HIPEC, anti-PD-1 and anti-HER-2 therapy, which will provide a clinical basis for the treatment of advanced GC.

The Efficacy and Safety of HIPEC Combined With PD-1 and SOX Chemotherapy for the Translational Treatment of GC or EGJC With PM

The Efficacy and Safety of HIPEC Combined With PD-1 and SOX Chemotherapy for the Translational Treatment of Gastric or Esophagogastric Junctional Cancer With Peritoneal Metastasis: A Prospective, Multicenter Phase II Study

The proportion of patients still alive at one year from the start of patient enrollment was calculated as a percentage of all patients. Deaths from all causes were included in the calculation of overall survival. The OS of patients who did not reach the one-year loss to follow-up was counted as data censored at the time of last confirmed survival before the loss to follow-up, i.e., only the time point of last known survival was counted in the number of survivors.

Percentage of all patients who did not experience disease progression or death within one year from the start of patient enrollment. If disease progression is indicated by imaging, the date of disease progression will be the time of the imaging exam that clearly confirms disease progression. If disease progression was diagnosed by other clinical modalities, the date of diagnosis will be used as the date of disease progression. Patients who discontinued the trial (without follow-up imaging) for reasons other than disease progression and patients who received post-trial therapy will have the time of discontinuation of the trial or the time of initiation of post-trial therapy as the data censored. New onset of other tumors is not considered a disease progression event and is also not censored as data.

CC-0 indicates no residual tumor visible to the naked eye, CC-1 indicates residual tumor with a maximum diameter of \<2.5 mm, CC-2 indicates residual tumor with a diameter of more than 2.5 mm but \<25 mm, and CC-3 indicates residual tumor with a diameter of ≥25 mm. CC-0 and CC-1 are usually classified as complete cytoreduction.

Refers to the proportion of patients whose tumors shrank to a certain level and remained there for a certain period of time, and includes both CR (Complete Response) and PR (Partial Response) cases. Objective tumor remission was assessed using the Solid Tumor Remission Assessment Criteria (RECIST 1.1 criteria). Patients had to be accompanied by measurable tumor lesions at baseline, and the efficacy assessment criteria were classified as Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressed Disease (PD) according to the RECIST 1.1 criteria. Disease (PD).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Efficacy of Surgical Treatment After Neoadjuvant Chemotherapy Plus Intraperitoneal Immunotherapy Versus Chemotherapy Alone for Patients With Positive Wash Cytology Gastric Cancer	NCT02976142	Gastric Cancer,...	neoadjuvant che...	18 Years - 80 Years	Moscow Clinical Scientific Center
A Clinical Study of BioTTT001 in Combination With SOX and Toripalimab in Patients With Gastric Cancer	NCT06283121	Gastric Cancer,...	BioTTT001 intra... SOX regimen toripalimab	18 Years -	China Medical University, China
The Efficacy and Safety of HIPEC Combined With PD-1 and SOX Chemotherapy for the Translational Treatment of GC or EGJC With PM	NCT06427252	Gastric Cancer,...	HIPEC Systemic therap...	18 Years - 75 Years	The First Affiliated Hospital with Nanjing Medical University

Spots Global Cancer Trial Database for gastric cancer, metastatic