HIPEC Combined With Sintilimab for Gastric Cancer With Peritoneal Metastasis

Gastric Cancer Clinical Trial

Official title:

A Phase II Study of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Combined With Sintilimab in Gastric Cancer With Peritoneal Metastasis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05648487
• Other study ID #: HIPEC-10
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 1, 2023
• Est. completion date: December 31, 2027

Study information

• Verified date: December 2022
• Source: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Contact: Ziying Lei, Doctor
• Phone: (086)020-66673666
• Email: leiziyinggz[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the Safety and Efficacy of HIPEC Combined With Sintilimab for Gastric Cancer Patients with Peritoneal Metastasis.

Description:

Peritoneal metastasis is the most common pattern of disease relapse and is attributed to the dismal prognosis of the gastric cancer. The National Comprehensive Cancer Network (NCCN) guidelines suggest that systemic chemotherapy is the first-line standard strategy, and chemotherapy combined with trastuzumab for patients with positive HER-2. HIPEC can significantly improve survival in peritoneal metastasis from gastric cancer. PD-1/PD-L1 antibody has shown promising outcomes for unresectable or metastatic solid tumors. The present study aimed to evaluate the safety and efficacy of HIPEC combined with Sintilimab (Tyvyt®) in gastric cancer patients with peritoneal metastasis.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 46
• Est. completion date: December 31, 2027
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Advanced gastric (gastroesophageal junction) adenocarcinoma confirmed by histology;

2. Age 18-75 years, Male or Non pregnant female

3. ECOG (Eastern Cooperative Oncology Group) : 0~1;

4. Negative for HER-2 by IHC/FISH;

5. Peritoneal metastasis is confirmed by laparoscopic exploration, and the PCI=20;

6. Untreated (e.g. radiotherapy, chemotherapy, target therapy and immunotherapy);

7. Normal Bone marrow, liver and kidney function indices before the recruitment:

8. Expected survival= 12 week

9. Signed the Informed Consent Form, and blood and tissue samples can be obtained;

Exclusion Criteria:

1. Other distal metastases besides peritoneal metastases (e.g., liver, lung, pleural, brain, bone metastases, etc.);

2. Previous systemic therapy for gastric cancer;

3. Recurrent gastric cancer after surgery;

4. Cardiopulmonary dysfunction;

5. Immunosuppressive drugs(eg.Corticosteroids) were used within 14 days before treatment, eg.corticosteroids,

6. There is any active autoimmune disease or a history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or asthma in childhood have been completely relieved, and those who do not need any intervention after adulthood can be included Asthma requiring medical intervention with bronchodilator was not included.)

7. Allergy to the drugs in this protocol;

8. Patients with other diseases not suitable for inclusion, such as immune deficiency, active tuberculosis, hepatitis B (non-active hepatitis B surface antigen (HBsAg) carriers, hepatitis B virus titer <500IU/ml after treatment and with normal liver function can be included), hepatitis C virus positive;

9. A history of idiopathic pulmonary fibrosis, tissue pneumonia, drug pneumonia, idiopathic pneumonia, or r active pneumonia;

10. Other patients who were considered unsuitable for inclusion by the researchers;

Related Conditions & MeSH terms

• Gastric Cancer
• Neoplasm Metastasis
• Stomach Neoplasms

Intervention

Drug:
• HIPEC,anti-PD-1 antibody Sintilimab (Tyvyt®), Chemotherapy,Surgery
HIPEC: HIPEC is performed after laparoscopic exploration, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgical exploration. Chemotherapy(SOX) and anti-PD-1 antibody Sintilimab (Tyvyt®) treatment followed (4 cycles): SOX regimen: Oxaliplatin: 130 mg/m^2, IV, d1; S-1, 40-60 mg/m^2 bid, po, day 1-14, every 3 weeks for a total of 4 cycles; Sintilimab (Tyvyt®) 200mg fixed dose every 3 weeks, for a total of 4 cycles. Surgery: Imaging and secondary surgical exploration, assess the patient's condition and consider whether perform the cytoreductive surgery (resection of primary tumors and metastases). For patients undergoing surgery, HIPEC for three cycles followed, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgery; For inoperable patients, continue to use standard chemotherapy of guidelines recommend. After the surgery, continue to use standard adjuvant chemotherapy.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Affiliated Cancer Hospital & Institute of Guangzhou Medical University

References & Publications (6)

Al-Batran SE, Homann N, Pauligk C, Illerhaus G, Martens UM, Stoehlmacher J, Schmalenberg H, Luley KB, Prasnikar N, Egger M, Probst S, Messmann H, Moehler M, Fischbach W, Hartmann JT, Mayer F, Hoffkes HG, Koenigsmann M, Arnold D, Kraus TW, Grimm K, Berkhoff S, Post S, Jager E, Bechstein W, Ronellenfitsch U, Monig S, Hofheinz RD. Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial. JAMA Oncol. 2017 Sep 1;3(9):1237-1244. doi: 10.1001/jamaoncol.2017.0515. — View Citation

Bonnot PE, Piessen G, Kepenekian V, Decullier E, Pocard M, Meunier B, Bereder JM, Abboud K, Marchal F, Quenet F, Goere D, Msika S, Arvieux C, Pirro N, Wernert R, Rat P, Gagniere J, Lefevre JH, Courvoisier T, Kianmanesh R, Vaudoyer D, Rivoire M, Meeus P, Passot G, Glehen O; FREGAT and BIG-RENAPE Networks. Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer With Peritoneal Metastases (CYTO-CHIP study): A Propensity Score Analysis. J Clin Oncol. 2019 Aug 10;37(23):2028-2040. doi: 10.1200/JCO.18.01688. Epub 2019 May 14. — View Citation

Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III Trial Comparing Intraperitoneal and Intravenous Paclitaxel Plus S-1 Versus Cisplatin Plus S-1 in Patients With Gastric Cancer With Peritoneal Metastasis: PHOENIX-GC Trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. doi: 10.1200/JCO.2018.77.8613. Epub 2018 May 10. — View Citation

Jiang H, Yu X, Li N, Kong M, Ma Z, Zhou D, Wang W, Wang H, Wang H, He K, Li Z, Lu Y, Zhang J, Zhao K, Zhang Y, Xu N, Li Z, Liu Y, Wang Y, Wang Y, Teng L. Efficacy and safety of neoadjuvant sintilimab, oxaliplatin and capecitabine in patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: early results of a phase 2 study. J Immunother Cancer. 2022 Mar;10(3):e003635. doi: 10.1136/jitc-2021-003635. — View Citation

Okabe H, Ueda S, Obama K, Hosogi H, Sakai Y. Induction chemotherapy with S-1 plus cisplatin followed by surgery for treatment of gastric cancer with peritoneal dissemination. Ann Surg Oncol. 2009 Dec;16(12):3227-36. doi: 10.1245/s10434-009-0706-z. Epub 2009 Sep 24. — View Citation

Yang XJ, Huang CQ, Suo T, Mei LJ, Yang GL, Cheng FL, Zhou YF, Xiong B, Yonemura Y, Li Y. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol. 2011 Jun;18(6):1575-81. doi: 10.1245/s10434-011-1631-5. Epub 2011 Mar 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	R0 resection	the rate of R0 resection	3 months
Secondary	Overall survival time	Overall survival time(OS) refers to the time of first use of the drug to the time of death. At the end of the study, if the subject is still alive, refer the known "date of last survival of the subject" as the date of censoring.	2 years
Secondary	ORR	Objective response rate(ORR): ORR = (number of subjects with complete response (CR) + partial response (PR))/total number of subjects ×100%. Measurable lesion according to the RECISTv1.1	3 months
Secondary	Event-Free Survival	Defined as the interval between the first conversion therapy and the first recorded related events, including preoperative disease progression, postoperative disease recurrence, and death from any cause.	2 years
Secondary	Relapse-Free Survival	Defined as postoperative the first recorded postoperative recurrence of disease or death from any cause	2 years