FLOT Combined With PD-1 in the First-line Treatment of Patients With Advanced Gastric Cancer and Peritoneal Metastasis

Gastric Cancer Clinical Trial

Official title:

Docetaxel, Oxaliplatin, Fluorouracil (FLOT Regimen) Combined With Teriprizumab (PD-1) in the First-line Treatment of Patients With Advanced Gastric Cancer and Peritoneal Metastasis: an Open, One-arm, Exploratory Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04886193
• Other study ID #: GDPHCM-GI-04
• Status: Recruiting
• Phase: N/A
• Start date: April 16, 2021
• Est. completion date: May 2023

Study information

• Verified date: May 2021
• Source: Guangdong Provincial Hospital of Traditional Chinese Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study, patients with advanced gastric adenocarcinoma whose peritoneal metastasis and peritoneal nodule pathologically confirmed metastasis and/or exfoliative cytology were confirmed as the clinical stage of peritoneal metastasis, who had not received treatment before, were invited to participate in the study.To evaluate the surgical conversion rate and tumor regression grade (TRG grade) of patients with stage gastric cancer with peritoneal metastasis using docetaxel, oxaliplatin, fluorouracil (FLOT regimen) combined with teriprizumab (PD-1).

Description:

The study drugs in this study are docetaxel, oxaliplatin, 5-FU, leucovorin, tigio capsules and teriprizumab.

Dosage and dosing regimen for all research phases:

The enrolled patients will receive 4 cycles of FLOT regimen + teriprizumab treatment before surgery, and every 2 weeks is a treatment cycle (Q2W). The specific plan is as follows.

• FLOT: Docetaxel 50mg/m2 ivd d1 + oxaliplatin 85mg/m2 ivd d1 + leucovorin 200mg/m2 ivd d1 + 5-FU 2600mg/m2 civ 24h Q2W

• Treprizumab 3mg/kg, intravenously administered on the first day of each cycle, Q2W If the transformation is successful, the patient undergoes R0 surgical resection of D2 lymph node dissection for gastric cancer in accordance with the "Japanese Gastric Cancer Treatment Guidelines. Physician's Edition. 4th Edition". After the operation, the patient will continue to receive 4 cycles of FLOT treatment + Teripril Anti-treatment, the treatment plan is the same as before.

After completing the 4 cycles of treatment, oral Tiggio Capsule (S-1) and Teriprizumab were maintained for 1 year. The specific plan is as follows.

• Tiggio capsule (S-1) 40-60mg (BSA<1.25 m2: 40mg, 1.25 m2≤BSA≤1.5 m2: 50mg, BSA> 1.5 m2:

60mg) po bid d1-14 Q3W, continuous treatment for 1 year;

• Teriprizumab 240mg, intravenously, given on the first day of each cycle, Q3W, continuous treatment for 1 year.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 2023
• Est. primary completion date: May 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Informed consent of the patient;

2. 18 years old <age <80 years old;

3. The primary gastric lesion was diagnosed as gastric adenocarcinoma by endoscopic biopsy histopathology (papillary adenocarcinoma pap, tubular adenocarcinoma tub, mucinous adenocarcinoma muc, signet ring cell carcinoma sig, poorly differentiated adenocarcinoma por);

4. The clinical stage of laparoscopic exploration is peritoneal metastasis, peritoneal nodule pathologically confirmed metastasis and/or exfoliated cytology test positive for advanced gastric cancer patients;

5. Preoperative ECOG [Using the ECOG scoring standard Zubrod-ECOG-WHO (ZPS, 5-point method) developed by the Eastern Cooperative Oncology Group (ECOG)] Physical State Score 0/1;

6. Preoperative anesthesia risk score sheet (ASA score sheet) I-III;

Exclusion Criteria:

1. The pathology of the peritoneal nodule confirmed no metastasis, and the exfoliated cytology test was negative;

2. Pregnant or lactating women;

3. Suffer from severe mental illness;

4. Preoperative imaging or intraoperative exploration revealed that there have been distant blood metastases in the liver, lungs, and brain;

5. A history of other malignant diseases within 5 years;

6. A history of allergies to any component of teriprizumab, docetaxel, oxaliplatin, and fluorouracil;

7. A history of continuous systemic corticosteroid therapy within 1 month;

8. Complications of gastric cancer (bleeding, perforation, obstruction) requiring emergency surgery;

9. A history of unstable angina or myocardial infarction, or a history of cerebral infarction or cerebral hemorrhage within 6 months, and a lung function test FEV1 <50% of the expected value;

10. Have received any of the following treatments:

1. Have received anti-PD-1 or anti-PD-L1 antibody therapy in the past;

2. Have received any investigational drug treatment within 4 weeks before using the drug for the first time;

3. Enroll in another clinical study at the same time, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up;

4. Receive the last dose of anti-cancer treatment (including radiotherapy) within 4 weeks before the first use of the study drug;

5. Those who have been vaccinated with anti-tumor vaccines or the study drugs have been vaccinated with live vaccines within 4 weeks before the first administration;

6. Those who have undergone major surgery or trauma within 4 weeks before using the study drug for the first time.

Related Conditions & MeSH terms

• Chemotherapy
• Gastric Cancer
• Neoplasm Metastasis
• Stomach Neoplasms

Intervention

Drug:
• FLOT(Docetaxel+oxaliplatin+leucovorin+5-FU), Treprizumab, Tiggio capsule (S-1)
FLOT: Docetaxel 50mg/m2 ivd d1 + oxaliplatin 85mg/m2 ivd d1 + leucovorin 200mg/m2 ivd d1 + 5-FU 2600mg/m2 civ 24h Q2W Treprizumab 3mg/kg, intravenously administered on the first day of each cycle, Q2W Tiggio capsule (S-1) 40-60mg (BSA<1.25 m2: 40mg, 1.25 m2=BSA=1.5 m2: 50mg, BSA> 1.5 m2: 60mg) po bid d1-14 Q3W, continuous treatment for 1 year; Teriprizumab 240mg, intravenously, given on the first day of each cycle, Q3W, continuous treatment for 1 year.

Locations

Country	Name	City	State
China	Guangdong Province Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Guangdong Provincial Hospital of Traditional Chinese Medicine	Shanghai Junshi Bioscience Co., Ltd.

Country where clinical trial is conducted

China, 

References & Publications (14)

Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik — View Citation

Bismuth H, Adam R. Reduction of nonresectable liver metastasis from colorectal cancer after oxaliplatin chemotherapy. Semin Oncol. 1998 Apr;25(2 Suppl 5):40-6. Review. — View Citation

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epu — View Citation

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25. — View Citation

Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Ros — View Citation

Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. doi: 10.1016/S0140-6736(17)31827-5. Epub 2017 Oct 6. — View Citation

Kitayama J, Ishigami H, Yamaguchi H, Yamashita H, Emoto S, Kaisaki S, Watanabe T. Salvage gastrectomy after intravenous and intraperitoneal paclitaxel (PTX) administration with oral S-1 for peritoneal dissemination of advanced gastric cancer with malignant ascites. Ann Surg Oncol. 2014 Feb;21(2):539-46. doi: 10.1245/s10434-013-3208-y. Epub 2013 Aug 22. — View Citation

Muro K, Chung HC, Shankaran V, Geva R, Catenacci D, Gupta S, Eder JP, Golan T, Le DT, Burtness B, McRee AJ, Lin CC, Pathiraja K, Lunceford J, Emancipator K, Juco J, Koshiji M, Bang YJ. Pembrolizumab for patients with PD-L1-positive advanced gastric cancer — View Citation

Nakajima T, Ota K, Ishihara S, Oyama S, Nishi M, Ohashi Y, Yanagisawa A. Combined intensive chemotherapy and radical surgery for incurable gastric cancer. Ann Surg Oncol. 1997 Apr-May;4(3):203-8. — View Citation

Yamaguchi K, Yoshida K, Tanahashi T, Takahashi T, Matsuhashi N, Tanaka Y, Tanabe K, Ohdan H. The long-term survival of stage IV gastric cancer patients with conversion therapy. Gastric Cancer. 2018 Mar;21(2):315-323. doi: 10.1007/s10120-017-0738-1. Epub 2017 Jun 14. — View Citation

Yamamoto M, Sakaguchi Y, Matsuyama A, Yoshinaga K, Tsutsui S, Ishida T. Surgery after preoperative chemotherapy for patients with unresectable advanced gastric cancer. Oncology. 2013;85(4):241-7. doi: 10.1159/000354420. Epub 2013 Oct 4. — View Citation

Yonemura Y, Bandou E, Kawamura T, Endou Y, Sasaki T. Quantitative prognostic indicators of peritoneal dissemination of gastric cancer. Eur J Surg Oncol. 2006 Aug;32(6):602-6. Epub 2006 Apr 17. Review. — View Citation

Yoshida K, Yamaguchi K, Okumura N, Tanahashi T, Kodera Y. Is conversion therapy possible in stage IV gastric cancer: the proposal of new biological categories of classification. Gastric Cancer. 2016 Apr;19(2):329-338. doi: 10.1007/s10120-015-0575-z. Epub 2015 Dec 7. Review. — View Citation

Zurleni T, Gjoni E, Altomare M, Rausei S. Conversion surgery for gastric cancer patients: A review. World J Gastrointest Oncol. 2018 Nov 15;10(11):398-409. doi: 10.4251/wjgo.v10.i11.398. Review. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Surgical conversion rate	defined as the proportion of patients who have undergone R0 surgical resection after multidisciplinary assessment after completing 4 courses of conversion adjuvant therapy	2-3 months
Primary	TRG grade	tumor regression grade	2-3 months
Secondary	PFS	Progression-free survival	1 year
Secondary	OS	overall survival	1 year
Secondary	the incidence and severity of adverse events	the incidence and severity of adverse events	1 year