A Phase II Study of TACE Plus PD-1 Antibody in the Locally Advanced Stomach Adenocarcinoma

NCT04799548 | Recruiting Phase 2

• 1 other identifier: ZSGC-TACiE04
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a phase II, prospective, single-center, single-arm trial to evaluate the efficacy and safety of the combination of neoadjuvant transcatheter arterial chemoembolization (TACE) and PD-1 antibody Tislelizumab in the locally advanced stomach adenocarcinoma. The primary purpose of this study is to evaluate the pathologic complete response (pCR) rate of TACE plus Tislelizumab. The second purpose is to evaluate pathologic response rate (pRR), objective Response Rate (ORR), overall survival (OS) and progression-free survival (PFS) of the patients enrolled in this study.

Conditions

Advanced Gastric Cancer

Keywords

Stomach Cancer; transcatheter arterial chemoembolization; PD-1; PD-L1; neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• pathologic complete response (pCR) rate

  1 months

Secondary Outcomes (4)

• pathologic response rate (pRR)

  1 months

• objective Response Rate (ORR)

  1 months

• overall survival (OS)

  3 years

• progression-free survival (PFS)

  3 years

Study Arms (1)

neoadjuvant TACE plus Tislelizumab

EXPERIMENTAL

Drug: Transcatheter Arterial Chemoembolization; Drug: Tislelizumab

Interventions

Transcatheter Arterial Chemoembolization DRUG

Patients will sequentially receive one cycle TACE (3 weeks), one cycle SOX regimen (3 weeks), one cycle TACE (3 weeks) and one cycle SOX (3 weeks) regimen, a total of 12-week neoadjuvant therapy. TACE cycle: Day 1: trans-femorally performed with infusion of oxaliplatin (85 mg/m2) into tumor blood vessels. Then, Embosphere® Microspheres (300-500 μm) will be injected for embolism. Day 1-14: Oral Tegafur Gimeracil Oteracil Potassium Capsule 40-60 mg bid. SOX cycle: Day 1: Oxaliplatin 130mg/m2 intravenous. Day 1-14: Oral Tegafur gimeracil oteracil potassium capsule 40-60 mg bid.

neoadjuvant TACE plus Tislelizumab

Tislelizumab DRUG

PD-1 antibody Tislelizumab will be administrated by 200mg, ivgtt, q3w throughout 12-week neoadjuvant treatment.

neoadjuvant TACE plus Tislelizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged 18 to 75 years old;
• KPS score \>=80;
• Gastric adenocarcinoma diagnosed pathologically;
• According to endoscopic ultrasonography/enhanced CT/MRI/PET-CT examination and laparoscopic exploration, clinical staging is determined to be cT3/4aN+M0 (according to AJCC TNM 8th edition);
• According to the RECIST1.1 standard, there is at least one evaluable lesion in the abdominal CT/MRI;
• The surgeons participating in this study judged the lesion to be resectable;
• Physical condition allows the surgery;
• The blood routine and biochemical indexes of the subjects met standards within 7 days before enrollment:
• There are no serious concomitant diseases that make the survival time \<5 years;
• Female subjects with fertility are not allowed to get pregnant or breastfeeding;
• Be willing and able to comply with the plan and follow-up procedures during the research period.

You may not qualify if:

• There are any signs of distant metastasis or local unresectable factors;
• Those who are allergic to contrast agents;
• Those who have received cytotoxic chemotherapy, radiotherapy, immunotherapy or radical surgery for the treatment of this gastric cancer, except for corticosteroids;
• Patients who have active autoimmune diseases or have a history of autoimmune diseases but may relapse;
• Any active malignant tumors within 2 years, except the specific cancers under study in this trial and locally recurring cancers that have been cured (such as resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast cancer);
• There is uncontrollable pleural effusion, pericardial effusion or ascites that requires frequent drainage within 14 days before enrollment;
• Patients with gastrointestinal bleeding within two weeks prior to enrollment, or those with high bleeding risk as judged by the investigators;
• Gastrointestinal perforation and/or fistula occurred within 6 months before enrollment;
• Upper gastrointestinal obstruction or abnormal physiological function or suffering from malabsorption syndrome, which may affect the absorption of drugs;
• Weight loss \>=20% within 2 months before enrollment;
• A history of the following lung diseases: interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, acute lung disease, etc.;
• There are uncontrollable systemic diseases including diabetes, hypertension, etc.;
• Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis, HIV infection, etc.;
• Untreated patients with chronic hepatitis B or chronic HBV carriers with hepatitis B virus (HBV) DNA exceeding 500 IU/mL, or hepatitis C virus (HCV) RNA positive patients should be excluded;
• Any of the following cardiovascular risk factors (refer to Research Guide)

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

ZhongShan hospital Fudan university

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (6)

• Scharping NE, Menk AV, Whetstone RD, Zeng X, Delgoffe GM. Efficacy of PD-1 Blockade Is Potentiated by Metformin-Induced Reduction of Tumor Hypoxia. Cancer Immunol Res. 2017 Jan;5(1):9-16. doi: 10.1158/2326-6066.CIR-16-0103. Epub 2016 Dec 9.

  PMID: 27941003 BACKGROUND

• Su Z, Shu K, Kang M, Wang G. Pathological complete response from oral chemotherapy combined with trans-arterial chemotherapy and embolization in an unresectable gastric cancer patient: A case report. Medicine (Baltimore). 2019 Jun;98(25):e16075. doi: 10.1097/MD.0000000000016075.

  PMID: 31232946 BACKGROUND

• Wu ZF, Cao QH, Wu XY, Chen C, Xu Z, Li WS, Yao XQ, Liu FK. Regional Arterial Infusion Chemotherapy improves the Pathological Response rate for advanced gastric cancer with Short-term Neoadjuvant Chemotherapy. Sci Rep. 2015 Dec 1;5:17516. doi: 10.1038/srep17516.

  PMID: 26620627 BACKGROUND

• Zhang CW, Zou SC, Shi D, Zhao DJ. Clinical significance of preoperative regional intra-arterial infusion chemotherapy for advanced gastric cancer. World J Gastroenterol. 2004 Oct 15;10(20):3070-2. doi: 10.3748/wjg.v10.i20.3070.

  PMID: 15378797 BACKGROUND

• Friedlander M, Meniawy T, Markman B, Mileshkin L, Harnett P, Millward M, Lundy J, Freimund A, Norris C, Mu S, Wu J, Paton V, Gao B. Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trial. Lancet Oncol. 2019 Sep;20(9):1306-1315. doi: 10.1016/S1470-2045(19)30396-1. Epub 2019 Aug 1.

  PMID: 31378459 BACKGROUND

• Xu J, Bai Y, Xu N, Li E, Wang B, Wang J, Li X, Wang X, Yuan X. Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma. Clin Cancer Res. 2020 Sep 1;26(17):4542-4550. doi: 10.1158/1078-0432.CCR-19-3561. Epub 2020 Jun 19.

  PMID: 32561664 BACKGROUND

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Xuefei Wang, MD, phD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhaoqing Tang, MD, phD

CONTACT

86-13817125778; tang.zhaoqing@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2021
• First Posted: March 16, 2021
• Study Start: December 30, 2021
• Primary Completion: December 1, 2024
• Study Completion: January 1, 2026
• Last Updated: May 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)