HIPEC-AS in Patients With Peritoneal Metastasis of the Stomach or Esophagogastric Junction

Prospective Study With HIPEC-AS in Patients With Locally Advanced, Limited or Extensive Peritoneal Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

HIPEC-AS01 is an open, prospective, single-center phase II clinical study, which will include "cT4aNxM0, P0 or cTxNxM1, P1" patients with gastric or esophagogastric junction adenocarcinoma, to evaluate the efficacy and safety of systemic chemotherapy with HIPEC combined with AS in the perioperative period. Patients enrolled will be divided into three groups. Among them, group A is the patients with locally resectable GC; group B is patients with peritoneal metastasis stage P1a or P1b, group C is patients with peritoneal metastasis stage P1c. The primary purpose is to evaluate the 3-year overall survival rate.

Study Overview

• Status: Not yet recruiting
• Conditions: Stomach Neoplasms; Peritoneal Metastases
• Intervention / Treatment: Procedure: HIPEC; Drug: Paclitaxel-albumin; Drug: Tegafur-gimeracil-oteracil potassium; Procedure: Surgery+HIPEC

Detailed Description

HIPEC-AS01 is an open, prospective, single-center phase II clinical study, which will include Patients With cT4aNxM0, P0, or cTxNxM1*, P1 Adenocarcinoma of the Stomach or Esophagogastric Junction, to evaluate the efficacy and safety of systemic chemotherapy with HIPEC combined with AS in the perioperative period.

Patients enrolled will be divided into three groups. Among them, group A is the patients with locally resectable GC; group B is patients with peritoneal metastasis stage P1a or P1b, group C is patients with peritoneal metastasis stage P1c.

Intervention:

Group A: 1 cycle HIPEC+S-1 chemotherapy, sequential 3 cycles of chemotherapy (AS plan, Q21d × 3), surgery+HIPEC, sequential 3 cycles of chemotherapy ( AS plan, Q21d × 3).

Group B: 1 cycle HIPEC+S-1 chemotherapy, sequential 3 cycles of chemotherapy (AS plan, Q21d × 3), surgery+HIPEC, sequential 3 cycles of chemotherapy ( AS plan, Q21d × 3).

Group C: 1 cycle HIPEC+S-1 chemotherapy, sequential 3 cycles of chemotherapy (AS plan, Q21d × 3), HIPEC+S-1 chemotherapy, sequential 3 cycles of chemotherapy ( AS plan, Q21d × 3).

In this study, the patient's overall survival was the main evaluation index. It is estimated that the case recruitment will be completed in 2 years, and the follow-up time will be 3 years. The total sample size is approximately 157 cases.

• Study Type: Interventional
• Enrollment (Anticipated): 157
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xuefei Wang, MD; Phone Number: +86 13917270428; Email: wang.xuefei@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 years old ≤ age ≤ 75 years old;
2. The primary gastric lesion was diagnosed as gastric or esophagogastric junction adenocarcinoma (papillary adenocarcinoma, tubular adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, and poorly differentiated adenocarcinoma. )
3. The tumor is located in the stomach or esophagogastric junction (Siewert type II/III)
4. The preoperative clinical staging is cT4aNxM0, P0 or cTxNxM1*, P1 (*no other distant metastases except peritoneal metastasis)
5. Good bone marrow reserve function: HB≥90g/L; ANC ≥1.5×10*9/L; PLT ≥80×10*9/L
6. Good liver and kidney function reserve: BIL ≤ 1.5 times the upper limit of normal (ULN); ALT and AST ≤ 2.5×ULN; Crea≤1×ULN;
7. Good coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN, activated partial thromboplastin time (APTT) ≤ 1.5 times ULN
8. ECOG (Eastern Cooperative Oncology Group) physical status score 0-2;
9. No prior treatment of chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc;
10. Written informed consent.

Exclusion Criteria:

1. There are distant metastases other than peritoneal metastases;
2. Complications of gastric cancer require emergency treatment, such as bleeding, perforation, obstruction, etc.;
3. Suffer from other malignant tumors within five years;
4. Body temperature ≥38℃ or complicated with infectious diseases requiring systemic treatment;
5. If there is a history of uncontrolled epilepsy, central nervous system disease, or mental disorder, the investigator will determine whether the clinical severity hinders the signing of informed consent or affects the patient's compliance with oral medications;
6. Clinically serious (ie active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) grade II or more severe congestive heart failure, or severe arrhythmia requiring drug intervention, or recent history of myocardial infarction within 12 months;
7. Severe respiratory diseases;
8. Severe liver and kidney dysfunction;
9. Upper gastrointestinal obstruction or abnormal physiological function or malabsorption syndrome, which may affect the absorption of oral drugs;
10. Diseases such as severe diabetes, hyperthyroidism and hypothyroidism have not been clinically controlled.
11. Those who continue to use glucocorticoid therapy within 1 month (except for local application) or who require immunosuppressive therapy for organ transplantation;
12. Pregnant or lactating women;
13. The patient has participated or is participating in other clinical studies (within 6 months);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; patients with locally resectable GC (cT4aNxM0, P0) 1 cycle HIPEC+S-1 chemotherapy, sequential 3 cycles of chemotherapy (AS plan, Q21d × 3), surgery+HIPEC, sequential 3 cycles of chemotherapy ( AS plan, Q21d × 3)	Procedure: HIPEC; The abdominal cavity will be filled with paclitaxel 120mg/m2 heated at 43℃ for 1 hour with a hyperthermic circulation machine.; Other Names: Paclitaxel injection; Drug: Paclitaxel-albumin; albumin paclitaxel D1, D8; S-1: D1-D14; Drug: Tegafur-gimeracil-oteracil potassium; 40mg bid(BSA<1.5 m2) ，60mg bid(BSA>=1.5 m2); D1-D14, po, bid.; Procedure: Surgery+HIPEC; gastrectomy with D2 lymphadenectomy+HIPEC procedure
Experimental: Group B; patients with peritoneal metastasis stage P1a or P1b (cTxNxM1, P1a or P1b) 1 cycle HIPEC+S-1 chemotherapy, sequential 3 cycles of chemotherapy (AS plan, Q21d × 3), surgery+HIPEC, sequential 3 cycles of chemotherapy ( AS plan, Q21d × 3)	Procedure: HIPEC; The abdominal cavity will be filled with paclitaxel 120mg/m2 heated at 43℃ for 1 hour with a hyperthermic circulation machine.; Other Names: Paclitaxel injection; Drug: Paclitaxel-albumin; albumin paclitaxel D1, D8; S-1: D1-D14; Drug: Tegafur-gimeracil-oteracil potassium; 40mg bid(BSA<1.5 m2) ，60mg bid(BSA>=1.5 m2); D1-D14, po, bid.; Procedure: Surgery+HIPEC; gastrectomy with D2 lymphadenectomy+HIPEC procedure
Experimental: Group C; group C is patients with peritoneal metastasis stage P1c (cTxNxM1, P1c) 1 cycle HIPEC+S-1 chemotherapy, sequential 3 cycles of chemotherapy (AS plan, Q21d × 3), HIPEC+S-1 chemotherapy, sequential 3 cycles of chemotherapy ( AS plan, Q21d × 3)	Procedure: HIPEC; The abdominal cavity will be filled with paclitaxel 120mg/m2 heated at 43℃ for 1 hour with a hyperthermic circulation machine.; Other Names: Paclitaxel injection; Drug: Paclitaxel-albumin; albumin paclitaxel D1, D8; S-1: D1-D14; Drug: Tegafur-gimeracil-oteracil potassium; 40mg bid(BSA<1.5 m2) ，60mg bid(BSA>=1.5 m2); D1-D14, po, bid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year Overall Survival, OS	The time from the date of enrollment of the patient to the date of death or the date of the last follow-up	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year Progression Free Survival, PFS	The time from the date of enrollment of the patient to the first occurrence of disease progression or death from any cause.	3 years
NCI CTC Adverse Events Version 4.0	Safety of HIPEC-AS plan	1 year

Collaborators and Investigators

• Sponsor: Xuefei.Wang
• Investigators: Principal Investigator: Xuefei Wang, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2021
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2026

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: October 26, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Actual): October 27, 2021
• Last Update Submitted That Met QC Criteria: October 26, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: paclitaxel; Stomach Neoplasms; Hyperthermic Intraperitoneal Chemotherapy; Peritoneal Metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Stomach Neoplasms; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel; Tegafur
• Other Study ID Numbers: B2021-574

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No